DENTAL MANAGEMENT OF THE MEDICALLY COMPROMISED PATIENTS

Tsvetan Tsvetanov
Edited by: Professor Angel Bakardjiev DMD, DDS, PhD, EACMFS

1
Aknowledgements

It is a great pleasure to express my deepest gratitude to my editor Professor Angel

Bakardjiev DMD, DDS, PhD, EACMFS from Department of Oral Surgery for giving me his
guidance and support during these years. His encouragement has been extremely valuable for the
completion of this thesis.

2
Contents

Introduction.........................................................................................................................................6
1. Technical considerations...................................................................................................................7
2. Antibiotic premedication indications - Initiate preventive therapy................................................. 8
3.Dental management of the patients with cardiovascular diseases.....................................................9
a. Angina pectoris.................................................................................................................................9
b. Acute myocardial infarction (AMI)..................................................................................................9
c. Arrhythmias.....................................................................................................................................11
d. Heart failure (HF)...........................................................................................................................12
e. Arterial hypertension (AHT)...........................................................................................................13
f. Prevention of Bacterial Endocarditis..............................................................................................16
g. Prophylaxis Against Total Joint Replacement Infection................................................................20
4. Dental management and respiratory disorders...............................................................................21
a. Chronic obstructive pulmonary disease (COPD)...........................................................................21
b. Asthma............................................................................................................................................21
c. Pulmonary tuberculosis..................................................................................................................23
d. Obstructive sleep apnea syndrome (OSAS)...................................................................................24
e. Foreign body aspiration..................................................................................................................25
5. Dental management of patients with bleeding disorders................................................................26
a. Common blood laboratory tests......................................................................................................30
b. Common bleeding disorders...........................................................................................................34
c. Blood Vessel Wall Abnormalities...................................................................................................34
d. Thrombocytopenia..........................................................................................................................34
e. Thrombocytopathy..........................................................................................................................35
f. Inherited coagulation disorders.......................................................................................................46
g. Dental management of haematologic disorders – anaemia............................................................54
h. Dental treatment in patients with leukemia....................................................................................57
6. Dental management of patients with endocrine disorders..............................................................59
a. Hyperthyroidism.............................................................................................................................59
b. Hypоthyroidism..............................................................................................................................61
c. Hyperparathyroidism......................................................................................................................63
d. Hypоparathyroidism.......................................................................................................................65

3
e. Addison’s disease............................................................................................................................66
f. Addisonian crises............................................................................................................................68
g. Hyperadrenocorticism (Cushing’s syndrome)................................................................................69
h. Dental management of patients with diabetes mellitus..................................................................70
7. Dental management of patients with renal diseases.......................................................................79
8. Dental considerations in patients with liver disease.......................................................................88
a. Viral hepatitis.................................................................................................................................89
b. Alcoholic liver disease...................................................................................................................92
c. Non-alcoholic fatty liver................................................................................................................92
d. Cirrhosis.........................................................................................................................................93
e. Hepatocellular carcinoma..............................................................................................................93
9. Dental management in stroke patients.......................................................................................98
10. Medical management of the stroke patient................................................................................ 99
11. Dental management of the head and neck cancer patient treated with radiation therapy...........101
12. Oral Complications of Head and Neck RT.................................................................................103

a. Xerostomia and salivary gland hypofunction...............................................................................103

b. Radiation mucositis......................................................................................................................104
c. Oropharyngeal candidiasis (OPC)................................................................................................105
d. Dental caries.................................................................................................................................106
e. Periodontal disease.......................................................................................................................107
f. Osteoradionecrosis (ORN)............................................................................................................108
g. Trismus.........................................................................................................................................109
13. Pre-RT dental assessment and treatment....................................................................................109
14. Bisphosphonate-related osteonecrosis of the jaw (BRONJ)......................................................113
Summary..........................................................................................................................................115
References........................................................................................................................................116

4
 The present monograph is designed to instruct medical doctors, doctors of dental medicine,
oral surgeons and another specialists, for a behaviour in case of medically compromised patients.
Their dental treatment (bloodless or “blood”) is conducted to the background on acute, subacute and
chronic common disease. In these patients exist a risk from complications in associated with
anesthetic drugs or dental treatment, emotional stress priority and its consequences. According to
16
the risk, patients are divided into three risk categories (low, high, and very high risk levels). The
dental history should include questions related to current oral conditions such as periodontal disease
or oral ulceration and past dental treatment and potential complications from prior intervention
including treatment failure and the delivery of anesthesia or post-treatment medication. 6
When the current monograph was written there were two possible approaches to structure:
1. According to the kind of complications and incidents with following diseases exposed,
which are their background and predisposing factor.
2. Systematic diseases exposed lead to possible complications and incidents.

As an author I prefer the second point of view, because of prior dental treatment, dentist
should ask for a thorough medical history. The disadvantages of this approach is difficult to apply in
complicated cases.
The present monograph can't consider to comprehensive. Science continue to develop at
accelerated rates. All critic notes will be perceived with pleasure.

5
Introduction

According to Burgess J, Meyers AD. as of November 1, 2011 the world's population is

estimated to be 7 billion. Within this mass of humanity is a substantial number of people that are
elderly; the graying of the world's population is predicted to produce millions of individuals with
systemic medical conditions that can affect oral health and dental treatment. The dental
management of these medically compromised patients can be problematic in terms of oral
complications, dental therapy, and emergency care. 6
The first step in managing the patient with medical problems is acquiring a thorough health history;
the second step is for the clinician to fully understand the significance of the disease that may be
endorsed by the patient. Each identified condition can affect dental care in a unique manner. For
example, medication prescribed for a medical condition might produce a problem during the
administration of a local anesthetic, or it could interact with pain medication prescribed post
intervention. The dental clinician needs to understand the potential complications that can occur as
a consequence of dental treatment of a medically compromised patient and when pretreatment or
post-treatment medication or emergency care is indicated. Certain medically compromised patients
should only be treated in a hospital setting where emergency issues, should they arise, can be
immediately addressed and promptly attended to in a controlled manner. For example, the patient
with a significant bleeding problem or thrombocytopenia arising as a primary condition or
secondary to medication, radiation, or leukemia is best managed in an in-patient environment where
replacement of platelets can be provided before the procedure or afterwards if spontaneous bleeding
occurs (eg, following a tooth extraction).
Dental management of the medically compromised patient requires acquisition of a
complete health history of the patient. This should include documentation via questionnaire as well
as a verbal history. A comprehensive health history questionnaire should include questions about the
patients cardiovascular, hematologic, neural and sensory, gastrointestinal, respiratory, dermal,
mucocutaneous, and musculoskeletal, endocrine, and urinary systems as well as questions related to
sexually transmitted diseases, drug use (eg, alcohol, tobacco), allergies, x-ray exposure or treatment,
medications, and hospitalizations. Preferably an oral history should also be obtained as a review of
systems (ROS). This oral ROS often elucidates information that is only touched on by a
questionnaire.

6
1. Technical considerations

Examination of the patient with a history of medical problems should be more extensive
than that associated with the healthy patient. Physical assessment should include evaluation of the
patient’s general appearance (eg, weight, posture, skin, nails, eyes, lips), blood pressure and
temperature, pulse rate, respiratory rate, a thorough head and neck inspection (including assessment
of lymph nodes, salivary glands, otologic assessment, assessment of breath smell), and cranial nerve
examination.
In patients that present with problems identified at examination that have not previously
been reported to a health care practitioner the dentist can be instrumental in defining potential
pathology and making the appropriate referral for additional medical evaluation. Such patients
should be referred for medical assessment prior to dental treatment. 6

Assessment of The Medically Compromised Patient (MCP) - Guidelines:

1. Complete Health History;

a) Date of Last Physical Examination;
b) Name, Address and Tel of Specialists;
c) List of Medical conditions being treated;
d) List of medications;
e) Allergies and Medical emergencies experienced;
f) Hospitalizations.

2. Assessment and Management Tools: Lab. Tests: complete blood count (CBC) with Plat.
Count and white blood cells (WBC diff). Prothrombin time (PT)/ international normalized ratio
(INR); partial thromboplastin time (PTT); BT. Liver function tests (LFTs) and Hepatic Serology
Serum Creatinine. Fasting blood sugar test (FBS); postprandial glucose test PP and glycated
haemoglobin (HbA1C); CD4 count and Viral Load.
Thorough knowledge of Diseases and Medications. Thorough knowledge of Anesthetics,
Analgesics, Antibiotics.

Preparation for Dental Treatment: Determine the status of diseases. Are the diseases well
14
controlled or uncontrolled?

7
 Screening medically compromised patients goal: To evaluate any source of infection that
may compromise successful medical or surgical therapy and restore optimal oral health and
function.
1. Full mouth intra-oral radiographs plus panoramic radiograph (if dentulous);
2. Panoramic radiograph only if edentulous or not able to take intraoral films;
3. Thorough medical and dental history, including medications documented on our own dental
chart;
4. Complete dental charting, periodontal charting if appropriate, but periodontal probing of all
teeth will routinely be accomplished;
5. Physician consultation to corroborate medical history and coordinate dental and medical
care;
6. Arrange treatment;
7. Arrange followup.

2. Antibiotic premedication indications - Initiate preventive therapy (

Protocols for dental management of the medically compromised patient.
http://dentalclinicmanual.com/docs/medicallycompromisedpatients.pdf) 24
1. Prosthetic heart valves;
2. Heart murmurs, e.g. MVP (with incompetence) and history of rheumatic fever (RF),
rheumatic heart disease (RHD);
3. Patients with congenital heart disease;
4. Dialysis patients - those with A-V shunts and those on CAPD - Continuous ambulatory
peritoneal dialysis;
5. Organ transplant patients, pre-and post transplant - depends on “counts”;
6. Chemotherapy patients, including bone marrow transplant - depends on “counts”;
7. Artificial joint patients;
8. Poorly controlled diabetic patients;
9. Radiation therapy patients, depending on procedure;
10. Bisphosphonate therapy patients;
11. Down syndrome patients (many have cardiac defects);
12. Immunosuppressed patients (depending on treatment). 24

8
 Systemic diseases include:
1. Cardiovascular diseases;
2. Respiratory diseases;
3. Liver diseases;
4. Endocrine diseases;
5. Renal diseases;
6. Neurogenic diseases;
7. Sexually transmitted diseases;
8. Blood diseases;
9. Pregnancy and breast feeding.

Main signs and symptoms of cardiovascular diseases: Chest pain; Dyspnea; Cyanosis;
Palpitation; Syncope; Edema of ankles; Cold pale extremities; Clubbing fingers; Easy fatigue
3. Dental management of the patients with cardiovascular diseases
a. Angina pectoris;
b. Acute myocardial infarction (AMI);
c. Arrhythmias;
d. Heart failure (HF);
e. Arterial hypertension (AHT);
f. Prevention of Bacterial Endocarditis;
g. Prophylaxis against total joint replacement infection

a. Angina pectoris: It is a myocardial ischemia resulting from imbalance between coronary

blood flow and oxygen demand. 23
It is a symptom complex with recurring seizures of pain and distress. Constricted by spasm,
narrowed by coronary sclerosis, or occluded by a thrombus, the coronary blood supply becomes
inadequate, resulting in altered myocardial metabolism and pain. The heart muscle being overtaxed
experiences an oxygen deficiency and an accumulation of metabolic products which is believed to
be the cause of painful symptoms. The pain of angina pectoris may be severe and agonizing; it may
be felt as a generalized pressure over the chest or under the sternum. It may also be felt in the teeth,
lower jaw, clavical and shoulders, radiating down the left or both arms. 1
b. Acute myocardial infarction (AMI): According to Cruz-Pamplona M, Jimenez-

9
Soriano Y, Sarrión-Pérez MG. acute myocardial infarction is characterized by acute, sudden onset
and intense pain, of an oppressive nature, located in the retrosternal or precordial region, and can
irradiate to the arms, neck, back, jaw, palate or tongue. The duration is over half an hour, and the
pain does not subside with rest. The condition is accompanied by intense perspiration, nausea,
vomiting, dyspnea and imminent death sensation, though it can also manifest as sudden loss of
consciousness, mental confusion or weakness. The triggering stimuli are emotional stress, intense
physical exercise or the existence of concomitant disease or surgery. So-called silent infarctions in
turn are characterized by an absence of pain, and are more common in elderly individuals, in
women and in diabetic patients. The drugs used to treat AMI and administered for secondary
prevention purposes comprise beta-blockers, calcium antagonists and the angiotensin-converting
enzyme inhibitors (ACEIs). 10
Dental management: A patient who has suffered acute myocardial infarction is at a high risk
of suffering another infarction episode or severe arrhythmias. In dental practice a minimum safety
period of 6 months has been established before any oral surgical procedure can be carried out. In
this time, dental treatment should be limited to emergency procedures aimed at affording pain relief:
extractions, the drainage of abscesses and pulpectomies, preferably carried out in the hospital
setting. After this safety period, the treatment decision should be established on the basis of the
situation and medical condition of each individual patient. If the patient is receiving anticoagulants,
the international normalized ratio (INR) on the day of treatment should be determined, and
treatment should be provided within the recommended limits (< 3.5), with local hemostasis if
surgery is planned. If the patient is receiving antiplatelet medication, excessive local bleeding is to
be controlled. The local hemostatic measures that can be used comprise bone wax, sutures, gelatin
of animal origin (Gelfoam®), regenerated oxidized cellulose (Surgicel®), collagen, platelet rich
plasma, thrombin (Thrombostat®), fibrin sealants (Tissucol®), electric or laser scalpels,
antifibrinolytic agents such as tranexamic acid (Amchafibrin®) or epsilon-aminocaproic acid
(Caproamin®). (Table 1).

DENTAL MANAGEMENT IN PATIENTS WITH ISCHEMIC HEART DISEASE

- Consultation → type of heart disease, severity, time elapsed from the cardiological event, clinical
complications, treatment received.
Take the prescribed medication as usual
- If nitrates are used, the patient should bring them
- Take as a preventive measure before local anesthesia
- Take in case chest pain develops
If surgery is needed:Anticoagulated patient → determine INR on the day of treatment · Antiplatelet
patient → local hemostatic measures
- Before 4-6 weeks after infarction → only emergency procedures

10
 - Very anxious patients → premedication (5-10 mg of diazepam the night before and 1-2 hours
before treatment)
- Brief visits (less than 30 minutes) → avoiding early morning hours and late afternoon hours -
Anesthesia → not to inject into a blood vessel
→ a maximum of two carpules with vasoconstrictor
- If anesthetic reinforcement is needed: anesthesia without vasoconstrictor
- Patient in semi-supine position
- Patient should get up carefully → to avoid orthostatic hypotension
- Monitoring may be required: blood pressure and pulsioxymetric

Table 1. Summary of dental management in patients with ischemic heart disease. Source:
Cruz-Pamplona M, Jimenez-Soriano Y, Sarrión-Pérez MG. 10

c. Arrhythmias: Arrhythmias are variations in normal heart rate due to cardiac rhythm,
frequency or contraction disorders. Atrial fibrillation is the most common type of cardiac
arrhythmia, with a prevalence in the general population of 0.4%, though this percentage increases to
3.8% at 60 years of age and reaches 9% in individuals over 80 years of age. The frequency of
electric pulse generation in the sinus node ranges from 60-80 beats per minute (bpm) under resting
conditions and can increase to 200 bpm during physical exercise. Arrhythmias are generated when
electric pulse generation proves defective.
Dental management: Consultation with the supervising physician is advised in order to
know the current condition of the patient and the type of arrhythmia involved, as well as the
medication prescribed. It must be checked that the patient uses the medication correctly. Anxiolytics
can be used to lessen stress and anxiety. Short visits in the morning are to be preferred. Patient
monitoring, with recording of the pulse, is indicated before starting treatment. It is very important to
limit the use of a vasoconstrictor in local anesthesia, with the administration of no more than two
carpules. The treatment planned should not be too long or complicated. Although modern
pacemakers are more resistant to electromagnetic interferences, caution is required when using
electrical devices (e.g., ultrasound and electric scalpels) that might interfere with pacemakers –
particularly the older models, since most such devices developed in the last 30 years are bipolar and
are generally not affected by the small electromagnetic fields generated by dental equipment. It is
therefore important to know the type of pacemaker, the degree of electromagnetic protection of the
generator, and the nature of the arrhythmia. Pacemakers and automatic defibrillators pose a low risk
of infectious endocarditis, and do not need antibiotic coverage before dental treatment. If important
arrhythmia develops during dental treatment, the procedure should be suspended, oxygen is to be

11
provided, and the patient vital signs are to be assessed: body temperature (normal values: 35.5-
37ºC), pulse (normal values: 60-100 bpm), respiratory frequency (normal values in adults: 14-20
cycles or respirations per minute), blood pressure (normal values: systolic blood pressure under 140
mmHg and diastolic blood pressure under 90 mmHg). Sublingual nitrites are to be administered in
the event of chest pain. The patient should be placed in the Trendelenburg position, with vagal
maneuvering where necessary (Valsalva maneuver, massage in the carotid pulse region, etc.). The
dental team should be prepared for basic cardiopulmonary resuscitation and initiation of the
emergency procedure for evacuation to a hospital center, if necessary.
d. Heart failure (HF): Heart failure (HF) is defined as the incapacity of the heart to
function properly, pumping insufficient blood towards the tissues and leading to fluid accumulation
within the lungs, liver and peripheral tissues. According to Cruz-Pamplona M, Jimenez-Soriano
10
Y, Sarrión-Pérez MG. in Spain, heart failure causes about 19,000 deaths each year. The survival
of the affected patients is limited, due to the aggravating factors and concomitant pathologies they
typically present. Heart failure in turn is the end stage of other diseases such as ischemic heart
disease or arterial hypertension. Acute heart failure is triggered by cardiotoxic drugs or coronary
occlusion episodes. The most common causes are severe and prolonged arterial hypertension, valve
disease, ischemic heart disease and serious pericardial diseases. Acute heart failure typically
manifests as acute lung edema. Chronic heart failure in turn is associated to antecedents of arterial
hypertension and ischemic heart disease. Other causes are dilated myocardiopathy, valve disease,
alcohol-induced heart disease, cor pulmonale and hypertrophic and restrictive myocardiopathy.
Diabetes mellitus in turn leads to a 2.5- to 5-fold increase in the risk of developing chronic heart
failure. The management of these patients includes identification and correction of the causal
factors (e.g., arterial hypertension or valve disease), and changes in lifestyle (elimination of toxic
habits or modifications in diet). Drug treatment in the form of ACEIs (captopril, enalapril, lisinopril
and quinapril) in turn can be associated to diuretics (furosemide) and vasodilators (isosorbide
dinitrate and hydralazine).
Dental management: Consultation with the supervising physician is advised in order to
know the current condition of the patient and the medication prescribed. The patient should be
receiving medical care, and heart failure should be compensated. Dental treatment is to be limited to
patients who are in stable condition, since these individuals are at an important risk of developing
serious arrhythmias and even sudden death secondary to cardiopulmonary arrest. In patients with
heart failure, including those presenting palpitations, asthenia or dyspnea, it is important to only
provide emergency care, and to do so in the hospital setting. Anxiety and stress are to be avoided
during the visits, which in turn should be brief (less than 30 minutes) and are to be programmed for

12
the morning hours. The patient should be placed in the semi-supine position in a chair, with control
of body movements (which should be slow), in order to avoid orthostatic hypotension. In patients
administered digitalis agents (digoxin, methyldigoxin), the vasoconstrictor dose is to be limited to
two anesthetic carpules, since this drug combination can favor the appearance of arrhythmias. 10

Medications Used to Treat Heart Failure (Source: Ganda K.) 14

Digitalis is a Cardiac Glycoside. Mechanism of action:

Digitalis binds to and inhibits:
-The Magnesium and Adenosine Triphosphate dependent Sodium and Potassium ATPase; -This
increases the influx of Calcium ions;
-This in turn enhances myocardial contractility.
Digitalis and the AAA Guidelines
1. Avoid with Digitalis:
-NSAIDS: Decrease renal clearance of Digitalis; Macrolides and Tetracycline: Increase serum
levels of Digitalis, causing toxicity.
2. Use with Digitalis:
-Anesthetic:Mepivacaine;Analgesics:Acetaminophen,Acetaminophen+Codeine,
Acetaminophen+Hydrocodone,Acetaminophen+Oxycodone;Antibiotics:Penicillins,
Cephalosporins, Clindamycin. 14
Aspirin (acetylsalicylic acid) can lead to sodium and fluid retention, and therefore should
not be prescribed in patients with heart failure. In the event of an emergency (i.e., lung edema), and
after contacting the emergency service, the patient should be placed seated with the legs lowered,
and receiving nasal oxygen at a rate of 4-6 liters/minute. Sublingual nitroglycerin tablets are
indicated (0.4-0.8 mg), and the dose may be repeated every 5 or 10 minutes if blood pressure is
maintained. Acute lung edema manifests as sudden onset or progressive dyspnea, cough with
expectoration, cyanosis, skin coldness, intense perspiration and critically ill sensation. The patient
typically refers suffocation and laryngeal irritation, and the condition may simulate an asthma
attack.
e. Arterial hypertension (AHT): Arterial hypertension (AHT) is an important health
problem due to its high incidence and prevalence in the general population and the associated
increase in risk of suffering cardiovascular disease in the form of chest pain (angina), myocardial
infarction and cerebrovascular events (e.g., stroke). Arterial hypertension affects 6-8% of the

13
general population and is the most common cardiovascular risk factor in Spain, with a prevalence of
over 40% in patients over 35 years of age. The blood pressure values considered to be normal were
established by consensus as under 90 mmHg in the case of diastolic pressure, and under 140 mmHg
in the case of systolic pressure. The latest revision of the guides for the evaluation and management
of arterial hypertension of the National Committee on the Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure (JNC 7) introduced the term “pre-hypertension” in reference to
people with a systolic blood pressure of 120-139 mmHg or with a diastolic blood pressure of 80-89
mmHg. (Table 2).
Dental management (Source: Cruz-Pamplona M, Jimenez-Soriano Y, Sarrión-Pérez MG.)10
: A well controlled hypertensive patients does not pose a risk in clinical practice. Consultation with
the supervising physician is advisable in order to know the degree of hypertension control and the
medication prescribed at that time. The patient is to be instructed to take his or her medication as
usual on the day of dental treatment. Prior to such treatment, the patient blood pressure should be
recorded, and if the values are found to be high, the visit should be postponed until adequate
pressure control is achieved. It is preferable for the visits to be brief and in the morning. The
prescription of anxiolytic agents may prove necessary in particularly anxious patients (5-10 mg of
diazepam the night before and 1-2 hours before the appointment) before dental treatment, or
alternatively sedation with nitrous oxide may be considered. A good local anesthetic technique
should be performed, avoiding intravascular injection and using a maximum of two anesthetic
carpules with vasoconstrictor. If more anesthesia is needed, it should be provided without
vasoconstrictor. Absorbable suture are to be avoided with adrenalin. During treatment, sudden
changes in body position should be avoided, as they can cause orthostatic hypotension as a side
effect of the blood pressure lowering drugs. When the patient does not present good blood pressure
control, it is best to refer him or her to the physician in order to ensure adequate control before
dental treatment. In the case of emergency dental visits, treatment should be conservative, with the
use of analgesics and antibiotics. Surgery is to be avoided until adequate blood pressure control has
been secured. Certain nonsteroidal antiinflammatory drugs (NSAIDs), such as ibuprofen,
indomethacin or the naproxen, can interact with antihypertensive drugs (beta-blockers, diuretics,
ACEIs), thereby lowering their antihypertensive action. Normally more than five days of treatment
with both types of drugs are required for interactions to manifest; as a result, NSAIDs should not be
prescribed for longer than this five-day period.
1. Local anesthesia with vasoconstrictor: The existing controversy over the use of local
anesthesia with a vasoconstrictor is explained by the possible adverse effects of these
substances upon blood pressure and/or heart rate. However, different studies have shown

14
 that no significant increases in arterial pressure are induced by the use of anesthesia with a
vasoconstrictor in dental treatments. Patients with cardiovascular disease are at a greater risk
of massive endogenous adrenalin release secondary to deficient local anesthesia than of
reaction to the small amount of vasoconstrictor used in local anesthetics. In effect, pain is
responsible for endogenous catecholamine release, and this in turn can give rise to
hemodynamic alterations. Pain control is essential during dental procedures, and epinephrine
affords excellent bleeding control in the context of local anesthesia. Nevertheless,
vasoconstrictor use should be limited, taking care not to exceed 0.04 mg of adrenaline (2
carpules containing 1.8 ml of anesthetic with adrenalin 1: 100,000).
2. Hypertensive emergencies: In the case of a hypertensive emergency (>120/210 mmHg),
furosemide should be administered (40 mg, via the oral route). If this proves insufficient to
restore pressure control, captopril should be administered (25 mg via the oral or sublingual
route). If the blood pressure fails to decrease within 30 minutes after these measures, the
patient should be referred to the nearest Hospital Emergency Department.

CLASSIFICATION OF BLOOD PRESSURE IN ADULTS

CLASSIFICATION OF SBP (mmHg) DBP (mmHg)

BLOOD PRESSURE IN
ADULTS
Normal < 120 < 80
Prehypertension 120-139 80-89
AHT Stage 1 140-159 90-99
AHT Stage 2 ≥ 160 ≥ 100

Table 2. Classification of blood pressure in subjects over 18 years of age (National Committee
on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure), Source: Cruz-
Pamplona M, Jimenez-Soriano Y, Sarrión-Pérez MG. 10

All patients with cardiovascular disease can be managed using the following guidelines
(According to Waters BG.) 22 :
1. Properly assess the patient. This should include an assessment by the dentist and also a
medical consultation if required;
2. Establish what medications the patient is taking along with the dose and timing and note any
potential drug interactions and side effects;
2. Use short appointments (less than one hour), preferably in the morning;

15
 3. Premedication should be considered to alleviate anxiety. The intraoperative use of nitrous
oxide and oxygen is also a reasonable strategy for patients with cardiovascular disease,
particularly those with ischemic heart disease;
4. Effective local anesthesia is important in order to avoid undue stress during the appointment
as long as the guidelines for the administration of epinephrine are followed. The use of
epinephrine impregnated gingival displacement cord should be strictly avoided in patients
with cardiovascular disease;
5. For patients with angina pectoris, a fresh supply of nitroglycerin should be available at the
time of the appointment. Prophylactic nitroglycerin has been shown to be effective in the
prevention of both hypertension and angina pectoris during dental treatment. The
appointment should be terminated early if the patient becomes overly anxious. In the event
of cardiovascular symptoms during dental treatment, all work should be stopped.
Emergency measures should be instituted if necessary. Preparations for emergencies should
be undertaken by all dentists. The treatment of patients with cardiovascular disease is
relatively simple if the proper steps are taken. The use of blood pressure measurements on
all patients will help to screen for undiagnosed hypertension and all patients who are
potentially hypertensive should be referred for medical evaluation. A preventive approach to
the treatment of these patients will serve to prevent untoward outcomes and provide safe and
simple delivery of dental care for cardiovascular patients. 22

f. Prevention of Bacterial Endocarditis

Infectious endocarditis (IE) is an infrequent condition resulting from the association of

morphological alterations of the heart and bacteremia of different origins. It has been estimated that
14-20% of all cases of IE have a buccodental origin. Transient bacteremia is observed not only in
dental treatments such as tooth extractions (51-85%) or periodontal surgery (36-88%), but also
during tooth brushing (26%) or when chewing gum (17- 51%). The mortality rate is 5-11%.
Approximately 50% of all cases of infectious endocarditis are caused by Streptococcus viridians.
Infectious endocarditis is infrequent in young individuals, except intravenous drug abusers, which
represent a high risk group. In these latter subjects, infectious endocarditis is a serious problem,
with an estimated incidence of 1.5-3.3 per 1000 intravenous drug abusers, and an associated 5-10%
mortality rate. These figures are decreasing, however, probably as a result of changing habits aimed

16
at avoiding infection with the human immunodeficiency virus (HIV). Recurrent infectious
endocarditis is also commonly observed in these individuals. 10
The guidelines are meant to aid practitioners, but are not intended as the standard of care or
as a substitute for clinical judgment. The recommendations were formulated by the writing group
after specific therapeutic regimens were discussed. The consensus statement was subsequently
reviewed by outside experts not affiliated with the writing group and by the Science Advisory and
Coordinating Committee of the American Heart Association.

Major changes in the updated recommendations include the following:

a) emphasis that most cases of endocarditis are not attributable to an invasive procedure;
b) cardiac conditions are stratified into high, moderate, and negligible risk categories based on
potential outcome if endocarditis develops;
c) procedures that may cause bacteremia and for which prophylaxis is recommended are more
clearly specified;
d) an algorithm was developed to more clearly define when prophylaxis is recommended for
patients with mitral valve prolapse;
e) for oral/dental procedures the initial amoxicillin dose is reduced to 2 g, a follow-up antibiotic
dose is no longer recommended, erythromycin is no longer recommended for penicillin-allergic
individuals but clindamycin and other alternatives are offered;
f) for gastrointestinal and genitourinary (GI/GU) procedures, the prophylactic regimens have been
simplified. These changes were instituted to more clearly define when prophylaxis is/is not
recommended, improve practitioner and patient compliance, reduce cost and potential GI side-
effects, and approach more uniform world-wide recommendations.

Cardiac conditions for which prophylaxis is or is not recommended (Source: Protocols for
dental management of the medically compromised patient.
http://dentalclinicmanual.com/docs/medicallycompromisedpatients.pdf 24):
1. High Risk Category: Prosthetic cardiac valves, including bioprosthetic and homograft
valves; Previous bacterial endocarditis; Complex cyanotic congenital heart disease (e.g.
single ventricle states; transposition of the great arteries, tetralogy of Fallot); Surgically
constructed systemic-pulmonary shunts or conduits.

17
 2. Moderate Risk Category: Most other congenital cardiac malformations (other than above
and below); Acquired valvar dysfunction (e.g., rheumatic heart disease); Hypertrophic
cardiomyopathy; Mitral valve prolapse with valvar regurgitation and/or thickened leaflets
Endocarditis Prophylaxis Not Recommended Negligible Risk Category (No Greater Risk
than the General Population); Isolated secundum atrial septal defect; Surgical repair of atrial
septal defect, ventricular septal defect, or patent ductus arteriosus (without residua beyond 6
mo); Previous coronary artery bypass graft surgery; Mitral valve prolapse without valvar
regurgitation; Physiologic, functional, or innocent heart murmurs; Previous Kawasaki
disease without valvar dysfunction; Previous rheumatic fever without valvar dysfunction;
Cardiac pacemakers (intravascular and epicardial) and implanted defibrillators.

Dental procedures for which prophylaxis is or is not recommended:

-Endocarditis Prophylaxis Recommended1
1. Dental extractions;
2. Periodontal procedures including surgery, scaling and root planing, probing, recall
maintenance; Dental implant placement and reimplantation of avulsed teeth;
3. Endodontic (root canal) instrumentation or surgery only beyond the apex;
4. Subgingival placement of antibiotic fibers/strips;
5. Initial placement of orthodontic bands but not brackets;
6. Intraligamentary local anesthetic injections;
7. Prophylactic cleaning of teeth or implants where bleeding is anticipated

-Endocarditis Prophylaxis Not Recommended:

1. Restorative dentistry2 (operative and prosthodontic) with/without retraction cord3;
2. Local anesthetic injections (nonintraligamentary);
3. Intracanal endodontic treatment; post placement and buildup;
4. Placement of rubber dams;
5. Postoperative suture removal;
6. Placement of removable prosthodontic/orthodontic appliances;
7. Taking of oral impressions;
8. Fluoride treatments;
9. Taking of oral radiographs;
10. Orthodontic appliance adjustment;
11. Shedding of primary teeth.

18
1
Prophylaxis is recommended for patients with high and moderate risk cardiac conditions.
2
This includes restoration of decayed teeth (filling cavities) and replacement of missing teeth
3
Clinical judgment may indicate antibiotic use in selected circumstances that may create significant
bleeding (Table 3).

Situation Agent Regimen1

Standard general prophylaxis: Amoxicillin Adults: 2.0 g;
Children: 50 mg/kg PO 1hour
before procedure
Unable to take medications Ampicillin Adults: 2.0 g IM or IV
Children: 50 mg/kg IM or IV
within 30 minutes before
procedure
Penicillin-allergic: Clindamycin Adults: 600 mg;
Children: 20 mg/kg PO 1 hour
before procedure
Cephalexin2 Adults: 2.0 g;
Or Cefadroxil2 Children: 50 mg/kg PO 1 hour
before procedure
Azithromycin Adults: 500 mg;
Or Clarithromycin Children: 15 mg/kg PO 1 hour
before procedure
Penicillin-allergic and unable to Clindamycin Adults: 600 mg;
take medications Children: 20 mg/kg IV within 30
minutes before oral procedure
Cefazolin2 Adults: 1.0 g;
Children: 25 mg/kg IM or IV
within 30 minutes before
procedure

1
Total children's dose should not exceed adult dose.
2
Cephalosporins should not be used in individuals with immediate type hypersensitivity reaction
(urticaria, angioedema, or anaphylaxis) to penicillins.

Table 3. Prophylactic regimens for dental, oral, respiratory tract, or esophageal procedures
(no follow-up dose recommended), Source: Protocols for dental management of the medically
compromised patient. http://dentalclinicmanual.com/docs/medicallycompromisedpatients.pdf 24

19
 g. Prophylaxis against total joint replacement infection (Hupp JR, Ellis E, Tucker MR.)
15

Patients who have undergone total replacement of a joint with a prosthetic joint may be at
risk for hematogenous spread of bacteria and subsequent infection. These late prosthetic joint
infections result in severe morbidity because the implant is usually lost when infections occur.
There has been great concern that the bacteremia caused by tooth extraction may result in such
infections. However, the recent literature suggests that bacteremias from oral procedures are not
likely to cause prosthetic joint infections. It appears that the bacteremia after oral surgery is of a
transient nature and does not expose the implant and periimplant tissues to bacteria long enough to
cause infection.
In 2003 the American Dental Association (ADA) and the American Academy of
Orthopaedic Surgeons (AAOS) issued a revised joint recommendation concerning the management
of patients with prosthetic total joints. In 2009, the American Academy of Orthopaedic Surgeons
issued an advisory statement recommending that all patients with prosthetic joints receive
antibiotic prophylaxis before dental procedures, regardless of the length of time following
implantation.

The 3 recommendations of the American Dental Association and the American Academy of
Orthopaedic Surgeons are:
1. The practitioner might consider discontinuing the practice of routinely prescribing
prophylactic antibiotics for patients with hip and knee prosthetic joint implants undergoing
dental procedures. (Strength of Recommendation: Limited);
2. We are unable to recommend for or against the use of topical oral antimicrobials in patients
with prosthetic joint implants or other orthopaedic implants undergoing dental procedures.
(Strength of Recommendation: Inconclusive);
3. In the absence of reliable evidence linking poor oral health to prosthetic joint infection, it is
the opinion of the work group that patients with prosthetic joint implants or other
orthopaedic implants maintain appropriate oral hygiene. (Strength of Recommendation:
Consensus).

The first recommendation is classified as limited because the limited amount of currently
available reliable scientific evidence does not substantiate that dental procedures cause late
prosthetic joint infections.

20
The second recommendation is classified as inconclusive because the studies performed to date
have come to inconsistent conclusions, from which no clear recommendation can be generated.
The third recommendation is based upon the consensus of the expert panel, rather than on any
scientific studies. 15

4. Dental management and respiratory disorders

a. Chronic obstructive pulmonary disease (COPD)

Chronic obstructive pulmonary disease (COPD) is a general term used in reference to

respiratory disorders characterized by not totally reversible chronic pulmonary airway obstruction.
Representative examples of COPD are chronic bronchitis and lung emphysema. According to
Claramunt Lozano A, Sarrión Perez MG, Gavaldá Esteve C. COPD is an important public health
9
problem. The prevalence of the disease in the Spanish adult population is 9%, and it constitutes
the fourth most common cause of death in Spain and in the rest of the world. Patients with COPD
may experience worsening of respiratory function during dental treatment; a number of precautions
are therefore recommended. Specifically, it is advisable to treat the patient in the vertical position.
The way in which rubber dams are used should also be modified in some cases, since the patients
may complain that they produce a suffocating sensation. Specialized clinics are able to offer oxygen
equipment and personnel trained in its use. Hypnotics, narcotics, antihistamines and anticholinergic
agents are to be avoided. If the patient is receiving corticosteroids, supplements may be needed. In
the case of individuals receiving theophylline, macrolide antibiotics (erythromycin, clarithromycin)
are to be avoided. Ambulatory general anesthesia is totally contraindicated. On the other hand,
patients with COPD, particularly those admitted to hospital, can suffer infectious lung diseases
secondary to the aspiration of microorganisms in the presence of deficient periodontal conditions.
The teeth and periodontium can serve as a reservoir for respiratory infections. In this sense, loss of
alveolar bone has been associated to an increased risk of COPD. Smoking is an important risk
factor for both periodontitis and COPD.
b. Asthma
Asthma is a respiratory disease characterized by reversible, diffuse stenosis or stricture of
the peripheral bronchi, increased responsiveness or sensitivity to different stimuli, and frequently
also signs or laboratory test evidence of an allergic alteration. According to Claramunt Lozano A,
Sarrión Perez MG, Gavaldá Esteve C. asthma is a common condition, typically affecting children

21
and with a prevalence of 5-6%. Over half of all affected individuals are between 5-15 years of age. 9
A distinction is to be made between allergic and non-allergic asthma. Allergic (or extrinsic) asthma
is characterized by a family history of asthma, together with an increase in serum IgE titers. These
antibodies participate in type I hypersensitivity or immediate sensitivity reactions, and are produced
in response to exposure to antigens that access the body through the oral or parenteral route, or in
aerosol form. Non-allergic, idiosyncratic or intrinsic asthma in turn constitutes a respiratory
disorder manifesting in a heterogeneous group of patients with reversible and recurrent
bronchospasm in response to different stimuli such as physical exercise, the inhalation of cold air,
emotions, exposure to smoke, hypoxemia, stress, gastroesophageal reflux, etc. Patients with this
type of asthma can be sensitive to aspirin and nonsteroidal antiinflammatory drugs (NSAIDs). The
drugs used to treat asthma have been related to certain oral disorders such as xerostomia (dry
mouth), oropharyngeal candidiasis and an increased prevalence of caries (due to the use of
inhalatory β-agonists). The use of oral rinses after medication has been found to be of great help in
preventing oral mucosal alterations. Asthmatic patients can also suffer gingivitis, since they are
often oral breathers, and this condition together with a number of immunological factors can
contribute to increase gingival inflammation. Children with chronic medical problems requiring
longterm medication are at an increased risk of developing caries as a side effect of the treatment
received. A possible mechanism implicated in the development of caries could be the intervention
of β-agonists, exerting an effect also upon the salivary glands. The impairment of salivary secretion
is in direct relation to the drug dose, and the composition of saliva is also affected. Caries also result
from an increased presence of lactobacilli and Streptococcus mutans. Periodic dental examinations
and the application of fluor are advised in these individuals. Elective treatment should be carried out
in asymptomatic or controlled asthmatic patients. Table 4 shows a number of drugs used in dental
care and which have specific implications when dealing with asthmatic patients.

DRUGS TO BE AVOIDED IN ASTHMATIC PATIENTS

Drugs containing aspirin (10-28% of all asthmatics may not tolerate the latter)
Nonsteroidal antiinflammatory drugs (patients with intrinsic asthma).
Macrolide antibiotics in patients treated with theophylline. The serum methylxanthines levels
(theophylline) may be increased.
Opiates: these can cause respiratory depression and histamine release.
Local anesthetics: use solutions without adrenalin or levonordefrin, due to the sulfite preservative
contents.
If the patient is receiving prolonged systemic corticosteroid treatment, supplements may be needed

22
(prior to dental procedures that might cause stress).

Table 4. Drugs to be avoided in asthmatic patients, Source: Claramunt Lozano A, Sarrión

Perez MG, Gavaldá Esteve C. 9

Management of asthma attacks (Source: Claramunt Lozano A, Sarrión Perez MG, Gavaldá
Esteve C.) 9 : Breathing effort becomes audible in the presence of mild or moderate obstruction. The
typical symptoms of asthma are breathing difficulty (e.g., wheezing, dyspnea) and cough. The
simple establishment of an optimum patient-professional relationship contributes to minimize the
stress and nervousness associated to dental treatment. The critical moments of dental treatment in
which an asthma attack can be triggered are immediately after local anesthetic injection and those
maneuvers that cause stress – such as extractions, surgery, or dental pulp removal in endodontic
procedures. Table 5 presents the recommended guidelines during an asthma attack.

MANAGEMENT OF ASTHMA ATTACKS

1. Suspend the dental procedure and raise the patient to a comfortable position.
2. Establish and keep the airways free, and administer an inhalatory β2 agonist.
3. Administer oxygen with a mask. If no improvement is observed or the symptoms worsen,
administer subcutaneous epinephrine (1:1000 in solution, 0.01 mg/kg body weight, with a maximum
dose of 0.3 mg).
4. Notify the emergency medical service.
5. Maintain adequate oxygen levels until the patient breathes regularly and/or medical help arrives.

Table 5. Management of asthma attacks, Source: Claramunt Lozano A, Sarrión Perez MG,
Gavaldá Esteve C. 9

c. Pulmonary tuberculosis: Tuberculosis (TB) is one of the main causes of death

throughout the world. Approximately one-third of the world population is infected with
Mycobacterium tuberculosis. Tuberculosis can affect any body organ, though the lungs are the most
common location. At first exposure to the bacterium (primary infection with the Koch bacillus), the
latter induces a characteristic granulomatous reaction (tuberculous follicle or granuloma).
Oral tuberculosis (Source: Claramunt Lozano A, Sarrión Perez MG, Gavaldá Esteve C. 9):
Oral mucosal lesions of TB are more common in young patients. Only 0.05-5% of all cases of

23
tuberculosis involve oral manifestations. These lesions may be primary or (more often) secondary to
pulmonary tuberculosis, reflecting reactivation of the infection at a given moment, since the
bacteria remain latent even after clinical healing of the initial infection. The oral lesions manifest as
an irregular ulceration with polygonal margins, possible peripheral induration and a dirtyappearing
base. The clinical appearance of the lesions is very similar to that of squamous cell carcinoma; it is
therefore important to establish a correct differential diagnosis in such cases, based on a biopsy and
bacterial culture. Oral TB has been reported in mandibular bone, the tongue and, less frequently,
affecting the lips, palatine tonsils and posterior pharyngeal wall and parotid glands. There have also
been reports of cases in other soft tissue locations such as the cheek. When TB is suspected, it is
advisable to postpone all non-emergency dental treatment until the patient has been cured or is no
longer infectious. If emergency dental treatment proves necessary in patients with suspected TB or
active disease, the adoption of respiratory protection measures helps reduce the risk of exposure.
The dental professional must avoid inhaling the infectious droplets by wearing a protective face.
d. Obstructive sleep apnea syndrome (OSAS) results from intermittent and repeated upper
airway occlusion during sleep. Such occlusion results from inspiratory collapse of the pharyngeal
walls, with complete (apnea) or partial interruption of the airflow (hypopnea). According to
Claramunt Lozano A, Sarrión Perez MG, Gavaldá Esteve C. such apneic or hypopneic episodes
are of variable duration and have a different effect upon cardiorespiratory homeostasis. 9 Regarding
the physiopathology of OSAS, critical upper airway narrowing during sleep results in occlusion.
This phenomenon in turn is intensified in obese people or individuals with other respiratory
disorders such as asthma or COPD. Following obstruction, the sleeping patient may attempt to
increase the air inflow rate in order to maintain the required oxygen supply, resulting in noisy,
intense and increasing snoring that causes partial or complete awakening. This in turn leads to
tiredness and drowsiness in the daytime, together with a series of psychomotor effects that depend
on the severity of hypoxemia and the duration of drowsiness. At dental exploration, palpation of the
muscles of the head and neck is indicated in order to identify possible masses or tumors that might
be the cause of airway obstruction. Other possible contributing conditions are deviation of the nasal
septum, class II malocclusion, large gonial angles, the size of the tongue and its base, and the
oropharynx (size of the uvula, size and characteristics of the soft palate tissues). The dental
professional is often directly implicated in the management of patients with OSAS by preparing and
fitting oral devices designed to advance the mandible, applying anterior and inferior mandibular
traction. The basic purpose of these devices is to prevent the base of the tongue from coming too
close to the posterior oropharyngeal region, where obstruction can result.

24
• Tongue retainer: this device positions the tongue in a cup or bubble located between the anterior
teeth. The tongue is not maintained in this position for long during sleep; as a result, this type of
device is indicated in patients with brief periods of apnea.
• Mandibular advancing device: this element stabilizes the mandible both vertically and
horizontally. It also keeps the tongue away from the pharyngeal wall, since mandibular protrusion
induces relative advancement of the tongue (due to the insertion of the genioglossal muscle). Given
the relevance of respiratory disorders such as OSAS, dental professionals should be able to
promptly identify and treat the condition, thereby contributing to the integral management of these
patients.

e. Foreign body aspiration: According to Claramunt Lozano A, Sarrión Perez MG,

Gavaldá Esteve C. many dental materials and elements are of small size, and when exposed to
9
saliva it may be difficult to manipulate them correctly. When the patient is placed in the supine or
semi-raised position, such objects might be swallowed or aspirated into the oropharynx. Depending
on the size, shape and flexibility of the object, swallowing may pose only minimum risk or
potentially can prove fatal. Prevention is clearly the best approach in such cases, though adequate
and rapid intervention in the event of accidental aspiration is essential for ensuring patient safety.
When a foreign body is aspirated into the oropharynx, the patient should sit up and be instructed to
cough forcefully. The immediate priority is to ensure that the airways remain free. If breathing is
affected, clearly recognizable symptoms quickly develop, such as asphyxia, inspiratory stridor and
the need to breathe with accessory muscle support. If vigorous coughing is not effective, the
Heimlich maneuver should be used: with the patient in the standing position, we grasp him or her
from behind with both arms. In this position we apply pressure with one closed fist and the other
hand covering the fist. The fist is positioned with the thumb over the abdomen, and we press firmly
towards the center of the stomach, immediately below the ribcage. If this maneuver likewise proves
ineffective, the patient must be moved to the nearest emergency medical center as quickly as
possible. While waiting for patient transfer, the dental professional should apply vital support
measures, including airway permeation by means of a cricothyroidotomy, where necessary. If the
airway is not affected, the swallowed object should be recovered to thus calm the patient. If
retrieval of the object is not possible, the situation should be explained to the patient, and due chest
and abdominal X-rays and clinical evaluation in the hospital will help identify the location of the
object (Table 6). 9

25
 APPROACH TO FOREIGN BODY ASPIRATION
1. Raise the patient and instruct him or her to cough forcefully.
2. If breathing is affected (asphyxia, inspiratory stridor and the need to breathe with accessory
muscle support) and vigorous coughing proves ineffective, perform the Heimlich maneuver.
3. If this likewise proves ineffective, notify the emergency medical service immediately. While
waiting for patient transfer, apply vital support measures, including airway permeation by means of
a cricothyroidotomy, where necessary.
4. If the airway is not affected, the swallowed object should be recovered to calm the patient.

Table 6. Approach to foreign body aspiration, Source: Claramunt Lozano A, Sarrión Perez
MG, Gavaldá Esteve C. 9

5. Dental management of patients with bleeding disorders

Introduction
When a patient presents with a bleeding disorder, how should dental providers proceed to
manage the complexity of the case? Management of such medically-complex patients involves “an
understanding of basic physiology of hemostasis,” which can greatly enhance one's comprehension
of most bleeding and clotting disorders. In addition to this composite of knowledge, clinical
application of recent evidence-based recommendations can contribute to the management of these
patients who may potentially require specialized medical and/or dental care.

Normal Hemostasis: The Making of a Blood Clot (Source: D'Amato-Palumbo S. 12)

Hemostasis is defined as “the termination of a bleed by mechanical or chemical means or by
the complex coagulation [clotting] process of the body…” Composing of a coordinated sequence of
events, hemostasis consists of vasoconstriction of the blood vessel, platelet adhesion and
aggregation, and thrombin and fibrin synthesis. (Fig 1). The general sequence of events in
hemostasis is briefly presented by describing the three main phases: vascular, platelet and
coagulation phases.

26
 Fig. 1. Schematic of an Injury to Blood Vessel, Source: D'Amato-Palumbo S. 12

Vascular phase (According to D'Amato-Palumbo S. 12): Immediately, when blood vessels

are injured, vasoconstriction of the arteries and veins begins. Within the injured vessel wall,
exposure of subendothelial tissues, collagen, and basement membrane contribute to prothrombotic
activites. Clotting activities include platelet aggregation and adhesion via release of adenosine
diphosphate (ADP) and von Willebrand factor (vWF).
Additionally, the release of a tissue factor (formerly known as tissue thromboplastin) during this
phase initiates coagulation via the extrinsic pathway. At this point, the initial layer of the platelet
plug is established at the site of the injury.
12
Platelet phase (According to D'Amato-Palumbo S. ): “Platelets are cellular fragments
from the cytoplasm of megakaryocytes” that survive in the vascular system for 8–12 days. They are
essential for the clotting process in the blood. Primary hemostatic functions of platelets include:
maintaining the health of the inner lining of the vascular wall; formation of a platelet plug during
vessel wall injury; and initiation of the coagulation phase, which leads to the stabilization of the
platelet plug.
During the platelet phase, platelets become sticky and adhere to one another and to the site of injury
after contact with exposed collagen and subendothelial tissue component vWF glycoprotein Ib.
Additionally, Adenosine Di-phosphate (ADP) is released by exposed subendothelial tissues that
cause platelets to aggregate, change shape, release dense and a-granule contents and synthesize
thromboxane A2 that can further act as a feedback activator potentiating platelet responses by
binding to thromboxane receptor (TP). A product of platelets, thromboxane, causes another surge of
platelet aggregation.
In summary, platelets adhere to the damaged subepithelial surface, change shape, become sticky,

27
and aggregate to form a hemostatic platelet plug at the injured blood vessel site. Under these normal
conditions, adequate numbers and function of platelets are required, resulting in the primary
cessation of the bleed by the hemostatic platelet plug formation.
Coagulation phase (According to D'Amato-Palumbo S. 12): Virtually simultaneously with
the vascular and platelet phases, the extrinsic, intrinsic and common pathways, containing 12
circulating plasma proteins, (also termed plasma coagulation factors) are initiated. (Table 7). These
plasma proteins are produced in the liver. More specifically, of the 12 plasma proteins, factors II,
VII, IX and X are Vitamin-K dependent for synthesis. The coagulation factors (F) are activated in a
cascade-like manner within their respective pathways. The “faster” extrinsic pathway is initiated by
F-VII when exposed to a tissue factor (or a membrane protein) within the injured vessel; and the
intrinsic pathway is initiated when F-XII contacts with injury-exposed subendothelial tissues.
Subsequently, coagulation factors in the intrinsic pathway activate one another: F-XII activates F-
XI; F-XI activates-IX; and F-IX activates F-VIII. Both pathways merge and F-X is activated,
yielding the activation of the common pathway. Subsequently, prothrombin is converted to
thrombin; thrombin acts as a catalyst for the conversion of fibrinogen; fibrinogen is the precursor to
fibrin.

Intrinsic Extrinsic Common

List of 12 Circulating Coagulation Factors
Pathway Pathway Pathway
Factor I Fibrinogen P
Factor II Prothrombin P
Factor III Tissue Factor P
Factor IV Calcium P
Factor V Proaccelerin P
*
Factor VII Proconvertin P
Factor VIII Antihemophilic factor P
Factor IX Plasma thromboplastin P
Factor X Stuart-Power factor P
Plasma thromboplastin
Factor XI P
antecedent
Factor XII Hageman factor P

28
Factor XIII Fibrin-stabilizer factor P
* Factor VI is non–existent.
Table 7. Coagulation Phase, Source: D'Amato-Palumbo S. 12

Fibrin is thus converted to a stringy, insoluble protein that forms an intricate network of
minute delicate structures called fibrils. At this point, blood cells and plasma are enmeshed in the
network of fibrils to form the clot. Therefore, fibrils are responsible for tightly binding the platelet
plug, stabilizing the plug, and affixing it to the site of injury. Resulting in a semi-solid, gelatinous
mass, it is termed the hemostatic clot or thrombus. This definitive clot prevents blood from leaking
out of blood vessels after injury. Within approximately 9 to 18 minutes, the fibrin clot is produced.
(Fig. 2). Under these physiological conditions, it is important to note that too few platelets,
abnormal platelets, platelets that do not function normally, or deficiencies of clotting factors may
not form normal clots; thus, disorders of the hemostatic system can result.

Fig. 2. Coagulation Cascade, Source: D'Amato-Palumbo S. 12

Finally, anticlotting mechanisms (broadly termed fibrin degradation products) in the

fibrinolynic pathway are activated to prevent the formation of more clots and to allow for the
dissolution of the definitive clot. The expected outcome is accomplished: repair of the injured blood
vessel wall results and bleeding ceases.

29
 Laboratory Assessment of Hemostasis

Many of the bleeding disorders can be diagnosed and monitored by way of laboratory
testing. When a significant coagulation disorder occurs in the vascular or platelet phase a clinical
bleeding problem is observed immediately after injury, or during invasive medical or dental
procedures. Conversely, when a significant disorder affects the coagulation phase (clotting factors),
the clinical bleed will most likely not be observed until several hours or longer after the injury or
invasive procedure.
Various laboratory screening tests can be ordered by the dentist when the patient reports a bleeding
disorder, when the patient responds positively to a family history of a bleeding disorder; or when
the clinician observes a sign/symptom of a bleeding problem during the clinical exam. Patients
with unknown bleeding problems should be referred to their physician or to a hematologist for
further evaluation. Laboratory tests provide an assessment of adequate numbers of platelets, proper
functioning of platelets, sufficient levels of plasma coagulation factors, and proper functioning of
the fibrinolytic pathway. When evaluating defects in the hemostatic system prior to invasive dental
treatment, dental professionals should become familiar with the following common blood
laboratory tests.
a. Common blood laboratory tests
According to D'Amato-Palumbo S. Platelet Count is a routine blood laboratory test that
12
provides a quantitative assessment of circulating platelets in the vascular system. A normal
platelet count should be within the range of 150,000 to 450,000 cells/mm3 of blood. When the
platelet count is less than 100,000 cells/mm3, thrombocytopenia is diagnosed. Patients presenting
with a platelet count between 50,000 and 100,000 cells/mm3 will predictably bleed mildly with
severe trauma or with dental surgical procedures. When the platelet count is less than 20,000
cells/mm3 an excessive and prolonged bleed is predictable; thus, this high-risk condition will
require medical attention prior to dental invasive procedures. Ultimately, thrombocytopenia can
prevent the formation of a hemostatic plug, resulting in hemorrhage.
The Ivy Bleeding Time laboratory test has been routinely used as a screening test for assessing
adequacy of platelet function. Abnormal platelet function is termed thrombocytopathy. When
performed, the bleeding time test calculates the time required for a standard skin incision to stop
bleeding by the formation of a hemostatic plug. The normal range of the Ivy Bleeding Time test is
usually between 2 and 10 minutes.
Over the years, this test was presumed to provide a measurement of bleeding risk in patients by way
of a prolonged bleeding time result. Consequently, its current use and application have been deemed

30
very limited because of its recognized unreliability to predict bleeding risk based on an abnormal
test result. This test fails to produce quantifiable and useful information for several reasons.
The following major conclusions were drawn regarding this test (According to D'Amato-Palumbo
S. 12):
1. Given the normal results of a standard bleeding time test one cannot exclude the possibility
of a significant clinical bleed with invasive dental procedures.
2. Without a positive medical history finding related to a bleeding disorder/platelet disorder,
the bleeding time test is not a “useful predictor” of an excessive bleed when performing
invasive dental procedures; and
3. The results of a prolonged bleeding time cannot reliably identify patients who are taking
anti-platelet therapy; thus, a prolonged bleeding time cannot be linked to the ingestion of
aspirin or NSAIDs. Therefore, the bleeding time test is merely a tool to screen for platelet
disorders; it is not an effective clinical testing method for predicting the quantity of a bleed
associated with an increased bleeding time in such patients.
Platelet Function Analyzer (PFA-100) is a sophisticated laboratory screening testing devise
that is currently being used in place of the Ivy Bleeding Time test. Platelet function tests or platelet
function assay (PFA) evaluate the qualitative function of platelets.
According to D'Amato-Palumbo S. these tests provide an assessment of platelet adhesion,
platelet activation and platelet aggregation during the development of a platelet plug, or primary
12
hemostasis. Generally, these tests measure the time it takes for a clot to form (platelets to clump
together) to prevent blood loss as the closure time. The PFA test (and other platelet function tests)
has not been shown to predict the likelihood that a patient will bleed excessively during invasive
procedures; although, it's full clinical utility has yet to be established.
Prothrombin Time (PT), measures the patient’s ability to form a definitive clot by
monitoring the proper functioning of the extrinsic coagulation pathway (Factor VII) and the
common pathway (Factors V, X, prothrombin and fibrinogen). Factors VII, X and prothrombin are
Vitamin K-dependent for their synthesis and become unstable when coumarin-like drugs are
prescribed.
According to D'Amato-Palumbo S. a normal coagulation profile indicates adequate levels
or percentages of clotting factors in the extrinsic and common pathways. Generally, the laboratory
testing range is between 11–15 seconds.Testing results beyond 15 seconds indicate an abnormal or
prolonged PT. This outcome is indicative of deficient coagulation factors needed to form a fibrin
clot, resulting in a prolonged bleed in the body. An active bleed caused by anticoagulation therapy,
coumarin-like drugs, is most commonly monitored by the international normalized ratio (INR)

31
laboratory test. 12
International Normalized Ratio (INR): According to D'Amato-Palumbo S. in 1983, the World
Health Organization Committee on Biological Standards established a more precise laboratory
testing method, the INR, to monitor patients taking anticoagulation drugs (warfarin therapy). 12
Consequently, laboratory materials (thromboplastin reagents) and laboratory techniques were
internationally instituted for the purpose of standardizing the assigned values. Patients with a
normal coagulation profile result in an INR value of 1.0.The “low intensity” INR range is between
2.0 and 3.0; and the “high-intensity” INR range is between 2.5 and 3.5. What governs the intensity
of anticoagulation therapy? The intensity is determined by the patient’s predisposition to abnormal
clotting. Patients diagnosed at high risk clot formation, will require higher intensity of
anticoagulation. From a pharmacological standpoint, anticoagulant drugs inactivate Factor VII
within the extrinsic pathway by inhibiting Vitamin K action; Vitamin K is required by the liver to
synthesize Factor VII.
Activated Partial Thromboplastin Time (aPTT) also measures the patient’s ability to
effectively form a definitive clot by evaluating the effectiveness of the intrinsic and common
pathways of the coagulation cascade. It tests for deficiencies in the intrinsic pathway, specifically
factors VIII, IX, XI, XIII; and deficiencies in the common pathway, specifically factors V and X,
prothrombin and fibrinogen. A normal aPTT is usually 25 to 40 seconds. According to D'Amato-
Palumbo S. aPTT is the laboratory test most often used by physicians to monitor heparin therapy
and to diagnose the hemophilias, which result in a prolonged or increased aPTT time. 12
Thrombin Time laboratory test assesses the conversion of fibrinogen to insoluble fibrin by
adding thrombin to the patient’s blood sample. Specifically, this test bypasses the extrinsic, intrinsic
and common pathways to determine the stability of the clot. Normally, the range of this test is
between 9 and 13 seconds. A prolonged time, in excess of 16 to 18 seconds, is considered abnormal.
(Table 8).

*Normal Importance in
Measures Normal *Abnormal
Laboratory Tests Values/Ran Diagnosing
Function Values/Ranges
ges Bleeding Disorders
Assess
150,000 to
Adequate platelet thrombocytopenia
Platelet Count 450,000/m 100,000 cells/mm3
numbers or inadequate
m3
numbers of platelets
Ivy Bleeding Adequate platelet 2-10 Screening test for Prolonged time:
Time function minutes thrombocytopathy; >9-10 minutes

32
 von Willebrand’s
disease
Assess function
Discriminates
of platelets:
Platelet Function between normal and
attachment,
Tests abnormal function
activation, and
of platelets
aggregation
Assess the time it
takes to form a
Assess defects in
fibrin clot when
the extrinsic
calcium and
pathway of the
tissue factor are
coagulation system:
added to the
anticoagulant
Prothrombin Time plasma (extrinsic 11 to 15 Prolonged time:
therapy (warfarin);
(PT) pathway: seconds >30 seconds
Prothrombin
coagulation
deficiency, vitamin
function of factor
K deficiency; liver
VII; common
disease; antiplatelet
pathway: factors
drugs
V, X, prothrombin
and fibrinogen)
Coagulation INR greater than 1.2
function of the in patients not on
International extrinsic pathway: Monitors oral anticoagulation
Normalized Ratio Factors V, VII, X, 1.0 anticoagulation therapy. In patients
(INR) prothrombin and therapy: warfarin on anticoagulants,
fibrinogen therapeutic range is
between 2.0 and 3.5
Assess the time it
takes to form a
fibrin clot when
calcium and Assess defects in
partial the intrinsic
thromboplastin pathway of the
Partial
containing coagulation system:
Thromboplastin 25 to 40 Prolonged time:
phospholipids are anticoagulant
Time (activated seconds 45 to 50 seconds
added to the therapy (heparin);
aPTT)
plasma (intrinsic von Willebrand’s
pathway: disease; hemophilia
coagulation A and B
function of
factors VIII, IX,
XI and XII
Thrombin Time Thrombin is 24 to 35 Assess defects in Prolonged or
added to blood to seconds the conversion of beyond normal
convert fibrinogen to fibrin

33
 fibrinogen to
fibrin
*Normal values or ranges may vary among different laboratories.
Table 8. Blood Laboratory Tests that Evaluate Hemostasis and Bleeding Disorders, Source:
D'Amato-Palumbo S. 12

b. Common bleeding disorders

Excessive or prolonged bleeding may result from (According to D'Amato-Palumbo S. 12):

1. Extremely fragile blood vessels;

2. Decreased number of platelets or impaired platelet function;
3. Abnormalities in the blood clotting coagulation factors;
4. Defects in the fibrinolytic pathway; or
5. A combination of these.
The following information provides an overview of the various abnormalities in the
hemostatic system.
c. Blood vessel wall abnormalities: According to D'Amato-Palumbo S. blood vessel wall
abnormalities, or increased fragility of the blood vessels, are relatively common but do not usually
12
cause a serious bleed. When evaluating the laboratory tests for this condition, one can expect a
normal platelet count, bleeding time and coagulation times (PT and aPTT). Pathophysiologically,
this condition manifests itself by observable extraoral and intraoral signs of hemorrhage: petechiae
and ecchymosis are found in the skin or on the mucous membranes, particularly on the gingiva.
Very rarely, significant hemorrhage may occur, particularly in the joints, muscles, and subperiosteal
locations. Excessive bleeding may also take the form of menorrhagia (abnormal long and heavy
menstrual periods), nosebleeds, gastrointestinal bleeding, or hematuria (abnormal presence of blood
in the urine).
Causes of Blood Vessel Wall Abnormalities (According to D'Amato-Palumbo S. 12)
•Infections (i.e., septicemia, infective endocarditis, several forms of rickettsioses)
•Drug reactions (i.e., hypersensitivity vasculitis)
•Scurvy, Henoch-Schönlein purpura
•Hereditary hemorrhagic conditions.
d. Thrombocytopenia: According to D'Amato-Palumbo S. the important role of platelets
in hemostasis is to form the temporary hemostatic plug, primarily requiring a sufficient number of
12
platelets. When a quantitative reduction of platelets exists, it can result in a significant cause of

34
generalized bleeding. Patients presenting with a platelet count of less than 100,000 cells/mm3 are
diagnosed with thrombocytopenia. When the platelet count is under 50,000 cells/mm3, bleeding
will be excessive postoperatively; thus, a platelet transfusion may be necessary prior to invasive
treatment. Moderate to severe thrombocytopenia (less than 50,000 cells/mm3) is usually manifested
by petechiae in the skin or on the mucous membranes; purpura or ecchymoses on the skin;
spontaneous mucosal bleeding; or intracranial hemorrhage. In the oral cavity, bleeding gingiva is a
common sign, spontaneous bleeding associated with brushing or flossing may be observable, and
bleeding from teeth extractions is possible. This condition is diagnosed by a platelet count
laboratory test, or by a complete blood count (CBC). Depending on the cause, thrombocytopenia
can be a consequence of increased platelet destruction, decreased platelet production, decreased
platelet survival, or increased splenic sequestration.
Thrombocytopenia is the leading cause of bleeding disorders, as presented in the following
major categories (Source: D'Amato-Palumbo S. 12):
1. Causes of Decreased Production of Platelets;
2. Generalized diseases of the bone marrow; Aplastic anemia;
3. Drug-induced thrombocytopenia: Cytotoxic drugs, Alcohol, Thiazide diuretics;
4. Infections: measles, HIV;
5. Ineffective megakaryopoiesis;
6. Causes of Platelet Destruction or Decreased Platelet Survival;
7. Immunologic destruction: Immune thrombocytopenic purpura (ITP);
8. Infections: HIV, infectious mononucleosis, cytomegalovirus (CMV);
9. Drug-associated: Quinine or quinidine, Methyldopa, Sulfonamides, Heparin, Gold, D-
penicillamine, Þ-aminosalicylic acid;
10. Nonimmunologic destruction: Thrombotic thrombocytopenic purpura, Giant hemangiomas,
Hemolytic anemias.

e. Thrombocytopathy (Source: D'Amato-Palumbo S.): Thrombocytopathy is characterized

12
by impairment in platelet function, but adequate numbers of platelets are normally present.
Thrombocytopathy may be congenital or acquired. The PFA-100 test (or other platelet function
tests) provides an assessment of the adequacy of platelet function, and contributes to the diagnosis
of the following disorders:
Causes of Platelet Destruction or Decreased Platelet Survival
•Inherited disorders: von Willebrand’s disease: consists of a platelet dysfunction and a Factor VIII

35
deficiency (Refer to inherited coagulation disorders)
•Acquired disorders: Drug-induced defects: *Aspirin (antiplatelet), **Nonsteroidal anti-
inflammatory drugs (NSAIDS), ***Other antiplatelet drugs; Alcohol in combination with aspirin or
NSAIDS; Uremia; Myloproliferative disorders
*Aspirin and aspirin-containing drugs are by far the most common reason for platelet dysfunction,
frequently resulting in a prolonged bleeding time. Aspirin, a nonsteroidal salicylate, acts as an
inhibitor of cyclooxengenase; thus, inhibits the synthesis of prostaglandins and interferes with the
production of thromboxane A2.The net result of aspirin therapy is to inhibit platelet aggregation,
hence, the formation of a platelet plug. (Fig. 3).

Fig. 3. The effect of aspirin on platelets, Source: D'Amato-Palumbo S. 12

Aspirin therapy, prescribed or self-administered, is a leading drug widely used by millions of
people in the U.S. for its cardioprotective properties. (Table 9). Its anti-platelet action prevents
thrombus formation by impairing platelet function and by interfering with their ability to form an
intact platelet plug. As a result, aspirin causes irreversibility of platelet function for the duration of
their lifetime, approximately 7–10 days. Use of aspirin therapy is indicated for primary and
secondary prevention of thromboembolism, myocardial infarction and cerebrovascular accident. 12

36
 Strategies to Address
Perioperative and
Postoperative Bleed
(For more information on
Effects on Dental Drug Products and Dental
Medication Indication for Use
Treatment Procedures Used as Local
Measures to Limit and
Control Bleeding During
Invasive Dental Procedures
see Table 3.)
Aspirin Treatment of mild-to- Key adverse event(s) • No specific remedy
moderate pain, related to dental
inflammation, and treatment: As with all • Consider platelet
fever; prevention and drugs which may transfusion ± DDAVP
treatment of acute affect hemostasis,
coronary syndromes, bleeding is associated • Normal platelet function
acute ischemic stroke, with aspirin. returns within 7 to 10
and transient ischemic Hemorrhage may days after discontinuation
episodes; management occur at virtually any
of rheumatoid arthritis, site; risk is dependent
rheumatic fever, on multiple variables
osteoarthritis; including dosage,
adjunctive therapy in concurrent use of
revascularization multiple agents which
procedures (coronary alter hemostasis, and
artery bypass graft, patient susceptibility.
percutaneous Many adverse effects
transluminal coronary of aspirin are dose
angioplasty, carotid related, and are rare at
endarterectomy), stent low dosages. Other
implantation. serious reactions are
idiosyncratic, related
to allergy or individual
sensitivity. See
clopidogrel.
Cilostazol Used for symptomatic No significant effects • No specific remedy
(Pletal) management of or complications
peripheral vascular reported. • Normal platelet function
disease, primarily returns within 4 days
intermittent after discontinuation
claudication.
Clopidogrel( To decrease the rate of a Aspirin in combination • No specific remedy
Plavix) combined end point of with clopidogrel
cardiovascular death, (Plavix®), prasugrel • Consider platelet
MI, or stroke. (Effient®), or transfusion ± DDAVP
ticagrelor (Brilinta™)
is the primary • Normal platelet function
prevention strategy returns within 7 to 10

37
 against stent days after discontinuation
thrombosis after
placement of drug-
eluting metal stents in
coronary patients. Any
elective surgery should
be postponed for 1
year after stent
implantation, and if
surgery must be
performed,
consideration should
be given to continuing
the antiplatelet therapy
during the
perioperative period in
high-risk patients with
drug-eluting stents.
Prasugrel(Ef To reduce the rate of See clopidogrel. • No specific remedy
fient) thrombotic
cardiovascular events • Consider platelet
(including stent transfusion ± DDAVP
thrombosis) in patients
who are to be managed • Normal platelet function
with percutaneous returns within 5 to 9
coronary intervention days after discontinuation
for unstable angina,
non-ST-segment
elevation MI, or ST-
elevation MI.
Ticagrelor(B Used in conjunction See clopidogrel. • No specific remedy
rilinta) with aspirin for
secondary prevention of • Consider aminocaproic
thrombotic events in acid, tranexamic acid,
patients with unstable recombinant factor VIIa
angina, non-ST-
elevation myocardial • Normal platelet function
infarction, or ST- returns within 3 to 5
elevation myocardial days after discontinuation
infarction managed
medically or with
percutaneous coronary
intervention and/or
coronary artery bypass
graft.
Ticlopidine Use platelet aggregation No significant effects • No specific remedy
inhibitor that reduces or complications
the risk of thrombotic reported; if a patient is • Consider platelet

38
 stroke in patients who to undergo elective transfusion ± DDAVP
have had a stroke or surgery and an
stroke precursors (Note: antiplatelet effect is • Normal platelet function
Due to its association not desired, ticlopidine returns within 5 to 10
with life-threatening should be discontinued days after discontinuation
hematologic disorders, at least 7 days prior to
ticlopidine should be surgery.
reserved for patients
who are intolerant to
aspirin, or who have
failed aspirin therapy);
adjunctive therapy (with
aspirin) following
successful coronary
stent implantation to
reduce the incidence of
subacute stent
thrombosis.

Table 9. Oral Antiplatelet Comparison Table, Source: D'Amato-Palumbo S. 12

Although the blood thinning properties of aspirin cause an increased risk of a clinical bleed, proper
management usually includes maintaining patients on “low-dose” aspirin therapy (75 to 100 mg) to
prevent the risk of a clot-threatening event. (Table 10).

Chemical Mechanism of
Brand Name Contradictions Disadvantages
Name Action
2” x 2” sterile
gauze pads;
place pressure
Gauze
on wound to
close or apply
finger pressure
Absorbable
Should not be
gelatin sponge
used under
material;
Gelfoam epithelial
provides stable
incisions or flaps,
'scaffold' for
inhibits healing
clot formation
Surgical Oxidized
regenerated
cellulose; exerts
physical effect
rather than

39
 physiological
Hemostatic
product
containing
microporus
poly-saccharide
No known
Bleed X hemispheres
contraindications
(potato starch);
dehydrates
blood and
accelerates
clotting
Technique sensitive:
Fibrin sealant; requires special
adhesive action attention to
Tisseel
that binds fibrin preparation;
to the clot reserved for
complex procedures
Used in the
form of a
mouthwash
after surgical
procedures to
inhibit
postoperative
Tranexamic
Cykloapron bleeding; can be
acid
administered
parenterally or
as an 4.8%
aqueous
solution (4
times daily for 1
week)
Apposition of
Suturing
soft tissue
Aminocaproic Antifibrinolytic No longer available
Amicar
acid agent for topical use
Tool to slow
intraoperative
Use cautiously to
bleeding and
Electrocautery avoid excessive
interfere with
tissue necrosis
postoperative
episodes

Every drug or dental product is not without side effects/adverse events or drug interactions;

40
dental provider must use dental drug reference prior to their use and/or consult with the patient's
supervising physician.
Table 10. Drug Products and Dental Procedures Used as Local Measures to Limit and Control
Bleeding During Invasive Dental Procedures, Source: D'Amato-Palumbo S. 12

In conclusion, it is recommended that a clinical bleed caused by routine dental extractions,

can be managed by standard local hemostatic measures (with direct packing of gauge, from suturing
to hemostatic agents). Additionally, it is recommended dental professionals adhere to the expert
opinion that the benefits of continuing antiplatelet therapy deceases the risk of a cardiovascular
episode. This strategy, therefore, outweighs the benefits of a decreased risk of bleeding
complications with surgery following cessation of aspirin (Source: D'Amato-Palumbo S. 12).
**Non steroidal anti–inflammatory drugs (NSAIDs) cause abnormal platelet function; thus,
bleeding tendencies can be expected. Once the drug is discontinued thrombocytopathy is reversed
within 1–5 half–life's of the drug. And, when considering aspirin and NSAIDs as pain relievers after
dental procedures, dental professionals should not prescribe these analgesics when optimum blood
clotting/hemostasis is desired.
***Other antiplatelet drugs irreversibly inhibit platelet aggregation, causing platelet dysfunction
(Table 9). Normal platelet aggregation/function returns when the antiplatelet drug is discontinued
and only when new platelets are produced, usually within a range of 3 to 10 days. It is
recommended that prescription antiplatelet drugs, when prescribed with or without aspirin, not be
discontinued for minor dental surgical procedures. However, more studies are needed to examine
the quantity of the bleed during major or complicated surgical dental procedures.Thus, prudent
treatment planning takes into account the use of hemostatic agents and dental procedures used as
local measures to control bleeding during and/or after the invasive dental procedure. (Table 10).

In the event these antiplatelet drugs are to be discontinued, it is prudent to consult with the
patient’s supervising physician or cardiologist, especially when patients present with coronary
artery stents: the American Heart Association strongly advises against the discontinuation of dual
antiplatelet therapy in patients with coronary artery stents within 12 months after placement. If
antiplatelet therapy (i.e., aspirin and clopidogrel) is suddenly discontinued it may increase the risk
of a fatal event in these patients.

41
 Coagulation Factor Disorders. Anticoagulation Therapy according to D'Amato-Palumbo S.
12

Warfarin Sodium is a coumadin derivative listed in the drug class as an oral anticoagulant. It
interferes with the liver’s synthesis of Vitamin K-dependent clotting factors; resulting in depletion
of blood clotting factors II, VII, IX, and X. Its therapeutic effect is to prevent further development
of the hemostatic plug; and it prevents new thromboembolic clot formation. Thrombosis is the
formation of abnormal blood clots (termed thrombi) that develop within the vascular system.
Thrombi are carried through the bloodstream (termed emboli) which can potentially occlude the
lumen of an artery or a vein and shut down a vital organ. The following conditions increase the risk
of a thromboembolic event: deep venous thrombophlebitis (inflammation of a vein); atrial
fibrillation (rapid, random contractions of the atria); myocardial infarction (heart attack);
mechanical heart valves (artificial heart valves); carotid artery disease; or peripheral vascular
disease. Additionally, clots form because there is an existing hypercoaguable condition where by the
blood has a tendency to clot more rapidly than normal, caused by either a blood vessel defect,
clotting factor abnormality or an immunologic abnormality.

When patients are taking warfarin therapy to prevent thromboembolic events, they are
monitored by the International Normalized Ratio (INR) laboratory test. The recommended INR
therapeutic range for patents on “low-intensity” warfarin therapy is between 2.0 to 3.0, with a target
goal of 2.5 INR. When patients are on “high-intensity” warfarin therapy, the INR range is between
2.5 to 3.5, with a target goal of 3.0 INR. Indications for placing patients in these ranges are
determined by the severity of the thromboembolic condition. (Table 11).

“Low Intensity” Warfarin Therapy “High Intensity” Warfarin Therapy INR

INR of 2.0 to 3.0, with a target of 2.5 of 2.5 to 3.5, with a target of 3.0

(5-7mg/day for 3-6 months) (7-10mg/day, long term)

• Prophylaxis of venous thrombosis (high • Mechanical prosthetic heart values

risk surgery)
• Prevention of recurrent MI
• Treatment of pulmonary embolism
• Treatment of thrombosis associated with
• Prevention of systemic embolism antiphospholipid antibodies

• Tissue heart valves in aortic or

mitral position for the first 3 months

42
 • Tissue valves with history of
pulmonary embolism

• Tissue heart valves with atrial

fibrillation

• Acute MI

• Atrial fibrillation

• Valvular heart disease

• Mitral valve prolapse with history of

atrial fibrillation or embolism

Table 11. Recommended Therapeutic Range for Warfarin Therapy, Source: D'Amato-
Palumbo S. 12

According to D'Amato-Palumbo S. historically, anticoagulation profiles for patients were

much higher. 12 Thus, it was necessary to discontinue or alter the warfarin therapy to avoid the risk
of an excessive bleed (hemorrhage) during and post invasive surgical and non-surgical procedures.
Rationale for this practice: Since Coumadin has a slow onset of action and a half-life of 36 hours it
requires complete withdrawal of the drug two to three days prior to the invasive procedure.
Consequently, patients' coagulation profiles resulted in suboptimal therapeutic levels, and possibly,
placed patients at risk for a thromboembolic event. More specifically, the following clinical
guidelines summarize dental management strategies for patients on Coumadin therapy who are
anticoagulated in the “low intensity” and “high intensity” therapeutic ranges, and who are scheduled
for various simple and complex surgical and non-surgical procedures:
Low intensity INR 2.0-3.0
•Consult with the patient's physician and obtain recent INR laboratory results prior to the invasive
dental procedure. It is important to obtain an INR lab result within 24 hours of highly invasive
procedures.
•If the INR is between the range of 2.0-3.0:
•When performing highly invasive non-surgical or simple surgical procedures, one can proceed if
the INR is within therapeutic range 2.0-3.0. (Non-surgical invasive procedures can include
subgingival debridement with slight to moderate inflammation.) Proceed with attention to control

43
bleeding with standard local hemostatic measures.
•If the INR is greater than 2.5:
•When performing complex surgical procedures or subgingival debridement with severe
inflammation, consult with the patient’s physician to allow the INR to drift down to a safe INR
range between 2-2.5. Proceed with attention to control bleeding with standard local hemostatic
measures.
•Considerations for transiently interrupting the anticoagulation therapy must be discussed with the
patient’s physician.
High intensity INR 2.5-3.5
•Consult with the patient’s physician and obtain recent INR laboratory results prior to the invasive
dental procedure.
•When performing non-surgical (subgingival debridement with sight to moderate inflammation) and
simple surgical procedures maintain INR in the 2.5-3.5 range; proceed with attention to standard
local hemostatic measures to limit and control bleeding.
•When performing complex surgical procedures or subgingival debridement with severe
inflammation consult with the patient’s physician; it may be safe to proceed in the lower ranges of
INR 2.5-3.0 with attention to local hemostatic measures. Considerations for transiently interrupting
the anticoagulation therapy must be discussed with the patient's physician.
•Consider use of low molecular weight heparin preparations to bridge the patient through the
invasive procedure as a substitute anticoagulant.
It can be concluded that most simple and routine invasive dental procedures can be safely
performed when the INR is ≤ 3.0/3.5; and it is advised not to proceed when the INR value is out of
range or when complex, surgical and non-surgical procedures are planned. When allowing for
higher normal therapeutic ranges of INR during invasive dental procedures, consider operator
experience. Under these conditions, it is prudent to consult with the patient’s supervising physician;
obtain results of an INR laboratory test within 24 hours of the invasive dental procedure; and be
prepared to use hemostatic measures to manage the expected clinical bleed for all planned dental
procedures.
While the current recommendations should be tailored towards the patients’ individual needs, dental
professionals must consider the following dental implications when treating anticoagulated patients:
•Identify the fundamental cause of the bleeding disorder for which anticoagulation therapy is
indicated.
•Consider operator experience with complex invasive dental procedures.

44
•Consider preexisting infection and/or the degree of inflammation of the soft tissues.
•Consider the extensiveness of the invasive procedure, especially significant soft tissue and bone
trauma.
•Consider bleeding management strategies and the availability of local hemostatic measures when
the risk of a bleed is expected.
•Consider the probable risk of inducing a thromboembolic event when discontinuing or altering the
anticoagulant drug; thus, resulting in coagulation profiles that are in the suboptimal therapeutic
range.
•Implement a heightened awareness when treatment planning: consider the complexity of the
invasive dental procedure; seek medical advice from the patient’s physician; and retrieve the results
of the most recent INR test.
Heparin: According to D'Amato-Palumbo S. managing dental patients on standard heparin
and low molecular weight heparin (LMWH) is important when providers need to control bleeding
12
during and following invasive dental procedures. Standard heparin itself is not considered an
anticoagulant but serves as the catalyst that inhibits plasma thrombin as well as coagulation factors
IX, X, XI, XII and plasmin; thus, preventing the conversion of fibrinogen to fibrin. LMWHs exert
their potentiating anticoagulant effects more so on factor Xa.
These drugs are used as a prophylaxis antithrombic agent and in the treatment of thromboembolic
disorders. Treatment with standard heparin usually consists of IV infusions in a hospital setting
which requires monitoring with the aPTT laboratory test. LMWH preparations are administered
subcutaneously on an out-patient basis. Their dosage is calculated based on the patient's body
weight and is given on an every 12-hour basis.
When considering substituting LMWH preparations, dalteparin (Fragmin), for Coumadin when a
dental surgical or nonsurgical procedure is planned, one must consult with the patient's physician to
strictly and safely manage the medication schedules. The following short-term heparinization
schedule is recommended: Coumadin is discontinued 4 days prior to the invasive dental procedure
and Fragmin is started. During this 4-day period Fragmin is administered every 12 hours. An
evening dose of Fragmin is administered on day 4; the invasive dental procedure is scheduled 12
hours after the evening dose of Fragmin. On the morning of the dental procedure Fragmin is held
back. During the evening of the surgical procedure both Fragmin and Coumadin are resumed and
continued until the INR is within the therapeutic range of 2.0-3.5. At this point, Coumadin is
continued and Fragmin is discontinued.

45
 f. Inherited coagulation disorders (Source: D'Amato-Palumbo S. 12)

A number of congenital blood clotting factor deficiencies exist; but three diseases account
for more than 90% of all inherited coagulant deficiencies. Deficiencies for discussion include:
Hemophilia A, Hemophilia B, and von Willebrand’s disease. These diseases can present with mild
to severe forms, which parallels the degree of deficiency of the blood coagulation factor.
12
Hemophilia A (Source: D'Amato-Palumbo S. ), also known as classic hemophilia, is
caused by a defect or a deficiency in the activity or the amount of factor VIII, respectively. This
hemophilia is a hereditary blood disorder that is transmitted as an X-linked recessive trait, thus,
predominately affecting males over females. Its incidence rate is about 1 in 5,000 male births. The
severity of this condition is related to the degree of the deficiency of factor VIII; therefore, the
greater the deficiency of the blood level factor the greater the bleed. Regarding hemostasis,
minimally 30% of factor VIII is required for normal activity. Approximately 60% of individuals
with hemophilia A possess a severe degree of deficiency, which is less than 1% of factor VIII.
(Table 12). It is diagnosed by a positive family history, a history of bleeding episodes and a
prolonged aPTT test with a normal PT test, along with inadequate levels of factor VIII. These series
of laboratory tests indicate a defective intrinsic coagulation pathway. When considering the
treatment planning for these patients, the dental professional should consult with the patient's
hematologist. Usually, treatment for a minor bleed includes hemostatic dental products, local
pressure, and/or cold compresses; treatment for an expected major bleed includes administration of
factor concentrates termed purified factor VIII products.

Classifications of Degree of
Risk of a Bleed After Trauma or Surgery
Hemophilia A and B Deficiency
Delayed onset of a bleed with trauma or
Mild 5% to 30%
surgery or dental extractions
Moderate 1% to 5% Excessive bleeding with surgery
Severe Excessive bleeding with trauma or surgery

Table 12. Classifications of Hemophilia A and B., Source: D'Amato-Palumbo S. 12

Clinical characteristics of Hemophilia A include: bleeding into joints (hemarthrosis),

commonly affecting knees, elbows and ankles; bleeding into soft tissues exhibiting extensive
ecchymoses; bleeding into a closed space such as muscle can lead to life-threatening blood loss;

46
intracranial bleeding; and bleeding into other sites such as gastrointestinal and urinary tracts.
Hemophilia B (Source: D'Amato-Palumbo S. 12), also known as Christmas disease or
plasma thromboplastin component deficiency, is transmitted in a sex-linked recessive fashion
similar to Hemophilia A. It is a bleeding disorder caused by a deficiency or defective factor IX
within the intrinsic pathway of the coagulation system. (Table 12). Not as prevalent as Hemophilia
A, Hemophilia B accounts for 10–15% of all hemophiliacs. It is diagnosed by a positive family
history, a history of bleeding episodes and a prolonged aPTT test with a normal PT test, along with
inadequate levels of factor IX. Replacement therapy for factor IX is more variable because factor IX
is distributed within and outside of the blood system, intravascular and extravascular respectively.
Although, both purified and recombinant factor IX products (or high-purity FIX [factor IX]
products) are recommended for the prevention or treatment of bleeding in patients with hemophilia
B. Clinical features of hemophilia B are similar to hemophilia A: they include: deep tissue
hemorrhage in joints, brain, and muscles.
von Willebrand’s Disease (vWD) is a disease that includes a composite of two disorders:

1. An inherited disorder of platelet adhesion, which involves a deficiency and/or a qualitative

defect in von Willebrand's tissue factor (vWF); and, in some cases,
2. Deficient or low levels of Factor VIII. Hence, this bleeding disorder leads to “a combined
defect in platelet plug formation and fibrin formation.”
vWD is one of the most common inherited bleeding disorders; it presents itself clinically by
spontaneous bleeding from “mucous membranes, excessive bleeding from wounds, menorrhagia,
and a prolonged bleeding time in the presence of a normal platelet count.” In most cases it is
transmitted as an autosomal dominant disorder, grouped into 3 major variants: Type I (deficiency in
vWF), Type II (qualitative defect in vWF), and Type III (both Type I and II defects), from a mild
form to a severe form. vWD is diagnosed by a positive family history; history of a serious bleed
from trauma or surgical procedures; spontaneous bleeding from mucous membranes, and laboratory
tests showing prolonged aPTT, abnormal assay results (a decrease in factor VIII level); prolonged
bleeding time and/or abnormal platelet function.
Bleeding management options depend on the clinical condition of the patient and the type of vWD
that is diagnosed (Type I, II or III). Such options include: Desmopressin, adequate plasma levels of
von Willebrand's factor, and factor VIII concentrates (FVIII).
Management and treatment of dental patients with inherited bleeding disorders present
unique challenges to the dental practitioner. Firstly, knowledge about the bleeding disorder and its
coagulation defect are necessary. Secondly, consultation with the patient’s hematologist should

47
direct the dental professional to perform the invasive dental procedure in the dental office or in the
hospital setting. This decision should be based upon the severity of the patient’s condition as well as
the possible need for infusion of factor replacement therapy. Lastly and extremely critical, treatment
planning must focus on individualized bleeding management strategies. (Tables 13 and 14). Hence,
comprehensive patient assessment, analysis of laboratory tests, collaboration with the supervising
physician, and careful treatment planning to include hemostatic approaches are important elements
in minimizing the bleed during and after invasive dental procedures.

Pre-treatment of invasive procedure: Management recommendations:

Hemophilia A:Factor VIII replacement,
Consult with hematologist
desmopressin (increases factor level)
Confirm diagnosis and severity of
e-aminocaproci acid (stablizes the clot)
hemophilia
Patients with mild to moderate
hemophilia are usually treated in the Hemophilia B: Purified Factor IX products
dental office
Patients with severe hemophilia are von Willebrand’s: Factor VIII replacement;
usually treated in a dental-based hospital vWF in some cases; and Hemophilia A
setting management recommendation

Table 13. Dental Management of Patients with Hemophilia., Source: D'Amato-Palumbo S. 12

Management during invasive Management after the procedure:

procedure:
Use good surgical technique
Use hemostatic agents
Hematologist will monitor hospitalized
patient
Monitor bleeding:
Hospitalize the pt if bleeding is not
controlled
Examine pt 24-48 hrs post procedure: treat
infection and/or bleeding issues
Avoid aspirin, use acetaminophen with or
without codeine

Table 14. Dental Management of Patients with Hemophilia., Source: D'Amato-Palumbo S. 12

48
 Patient and Clinical Assessment (Source: D'Amato-Palumbo S. 12)
Assessment should include a systematic approach of collecting, organizing, and evaluating
all patient data. Data must be retrieved from the personal, medical and dental histories, the
pharmacological history, laboratory testing, and inspection of the extra and intraoral structures. This
subjective and objective evidence is vital to the development of a proper treatment plan and dental
management of patients with bleeding disorders when performing invasive dental procedures. All of
these required pieces of information are essential when considering the legal and ethical
responsibilities health care providers must exercise when caring for their patients.
Examining the medical history questionnaire is the first step in identifying whether or not it
includes questions regarding the suspect or history of bleeding disorders. Questions should include
the following: the determination of a known history or a family history of a bleeding disorder,
history of bleeding episodes related to a dental procedure, areas of petechiae, purpura and
ecchymosis, easy brusing, frequent nose bleeds (epitaxis), blood in the urine (hematuria), clotting
problems, bleeding in the joints (hemarthrosis), deep muscle hematomas, excessive menstrual
bleeding, alcohol abuse problems, cirrhosis of the liver, and unusual bleeding following an injury or
a surgical procedure. A verbal inquiry or follow-up approach can include who, what, where, when,
why, or how questions. Such questions that pertain to bleeding disorders can include:

•What is the bleeding disorder?

•What is the etiology of the bleeding disorder?
•What are the hemorrhagic signs and symptoms? Location of the hemorrhagic signs and symptoms?
•What prescription medications, OTC dugs and/or supplements are being taken?
•What are the results of the blood laboratory tests?
•Who is the supervising physician, cardiologist or hematologist?
•When was the bleeding disorder diagnosed? (bleeding history and/or family history)
•What bleeding complications have been encountered?(specifically, spontaneous bleeding with
injury or a prolonged bleed related to dental or medical surgeries)
•How is the bleed medically or dentally managed?
Included in the pharmacological history the dental provider should query the patient about
prescription medications that cause bleeding tendencies, specifically anticoagulation therapy,
antiplatelet or nonsteroidal anti-inflammatory drugs, or heparin therapy. Just as important, patients
should be asked about taking over-the-counter drugs containing aspirin; and they should be
questioned about supplements and herbs that may exacerbate the bleed when patients are taking

49
anticoagulants. There are more than 200 over-the-counter aspirin-containing drugs available to
individuals as well as multiple combinations of herbal therapies that can affect the hemostatic
pathways. Following the patient and clinical assessments, dental professionals should perform a
thorough extraoral and intraoral examination to identify deviations from normal that are indicative
of bleeding disorders. Long-standing history of clinical findings in patients with mild to severe
bleeding disorders often result in petechiae, ecchymoses, spontaneous gingival bleeding, and
hemorrhages into the soft tissues. The most common oral finding associated with bleeding disorders
is petechiae, which present as purple or red, 1 to 2 mm spots that appear as a result of minute
hemorrhages within the dermal layers. Their locations are most often on the mucosal surfaces.
Ecchymoses, larger than petechiae, are flat, reddish blue or purplish discolorations of the skin or
mucosa. These hemorrhagic lesions result from spontaneous leakage of blood into the surrounding
tissues (extravasation). This severe bleeding results from trauma, including surgery, by underlying
blood vessels or by fragility of the vessel walls. In severe disorders, gingival bleeding may
spontaneously occur. Based on the outcome of the patient’s histories and head and neck (extra- and
intraoral) examination, positive findings relative to the suspicion of a bleeding disorder should
warrant a physician consultation and a laboratory screening evaluation. Hence, a proper diagnosis
can be made and optimal dental care can be provided.
Treatment Planning Considerations (Source: D'Amato-Palumbo S. 12)
Appropriate management for patients with bleeding disorders who require routine invasive dental
procedures, including subgingival debridement (scaling and root planing), restorative procedures or
simple surgical procedures, consists of the following:
Step 1: Take accurate, comprehensive histories: personal, medical, dental and
pharmacological. Perform a thorough extra and intraoral examination to identify lesions indicative
of a bleeding disorder. When a known bleeding disorder is evident, understand the pathophysiology
and its related impact on dental treatment. When an unknown bleeding disorder is suspected, refer
the patient to his physician or a hematologist to establish a diagnosis. Definitive diagnosis of the
bleeding/clotting disorder can be established by the physician or hematologist by ordering the
“Prolonged Clotting Time Profile” laboratory tests.
Step 2: Consult with the supervising physician to obtain additional information about the
patient’s disorder or bleeding history. Continue to investigate and/or to obtain medical clearance to
treat. Secondly, retrieve and evaluate the blood laboratory test results while scheduling the
appointment within 24 hours of the results.
Step 3: Develop an appropriate treatment plan: establish whether or not the invasive dental
procedure will be carried out in the dental office or in a hospital-based dental facility. Possibly, prior

50
to invasive treatment, consider blood and/or clotting factor replacement therapy for patients with
hemophilia; and patients with platelet disorders may require platelet transfusion therapy. In
addition, other medical interventions may be required beyond infusion therapies for the respective
disorders; for example, fibrinolytic defects, vascular defects or modification of anticoagulant
therapy may require specialized medical care. When performing the invasive dental procedure
recommendations include: minimize tissue trauma; consider hemostatic systems for predictable
extensive bleeding during and after complex surgical procedures; consider alternative pain control
techniques other than nerve-block anesthesia, especially for patients with coagulopathies;
emphasize periodontal health to minimize gingival inflammation which can result in increased
bleeding; and/or consider using a combination of local hemostatic systems to manage bleeding
episodes. Specialty dental procedures (restorative, endodontic or surgical) can adhere to these
fundamental guidelines in their approach to manage bleeding episodes, but most importantly,
various invasive oral procedures carry a range of bleeding risk.
When considering the management of a clinical bleed during various invasive dental
procedures, hemostatic measures can include the following systemic or local applications:
hemostatic irrigant; absorbable gelatin sponge containing a thrombin solution; gauze-soaked
squares and/or mouthrinses with fibrin or tranexamic acid (TXA); aminocaproic acid (EACA);
vasoconstrictors in local anesthetics; surgical techniques and sutures; ice packs; and/or a
combination of these measures. (Table 15).

Chemical Mechanism of
Brand Name Contradictions Disadvantages
Name Action
2” x 2” sterile
gauze pads;
place pressure
Gauze
on wound to
close or apply
finger pressure
Absorbable
Should not be
gelatin sponge
used under
material;
Gelfoam epithelial
provides stable
incisions or flaps,
'scaffold' for
inhibits healing
clot formation
Surgical Oxidized
regenerated

51
 cellulose; exerts
physical effect
rather than
physiological
Hemostatic
product
containing
microporus
poly-saccharide
No known
Bleed X hemispheres
contraindications
(potato starch);
dehydrates
blood and
accelerates
clotting
Technique sensitive:
Fibrin sealant; requires special
adhesive action attention to
Tisseel
that binds fibrin preparation;
to the clot reserved for
complex procedures
Used in the
form of a
mouthwash
after surgical
procedures to
inhibit
postoperative
Tranexamic
Cykloapron bleeding; can be
acid
administered
parenterally or
as an 4.8%
aqueous
solution (4
times daily for 1
week)
Apposition of
Suturing
soft tissue
Aminocaproic Antifibrinolytic No longer available
Amicar
acid agent for topical use
Tool to slow
intraoperative
Use cautiously to
bleeding and
Electrocautery avoid excessive
interfere with
tissue necrosis
postoperative
episodes

52
 Table 15. Drug Products and Dental Procedures Used as Local Measures to Limit and
Control Bleeding During Invasive Dental Procedures, Source: D'Amato-Palumbo S. 12

Every drug or dental product is not without side effects/adverse events or drug interactions;
dental provider must use dental drug reference prior to their use and/or consult with the patient's
supervising physician. More importantly, when selecting a hemostatic therapy that achieves
adequate hemostasis when performing invasive dental procedures on patients with bleeding
disorders one must consider the following elements:
•The specific bleeding disorder.
•The need for a hemostatic agent and/or intervention.
•The type of local and/or systemic hemostatic agent.
•The need for a consultation with the patient's supervising physician to determine the need for
coagulation factor replacement as indicated.
•The severity of the bleeding disorder.
•The specific invasive dental procedure that will induce a bleed intraoperatively and
postoperatively.

Conclusion

According to D'Amato-Palumbo S. in this continuing education course, learning

encompassed both the basic physiological events of hemostasis and the pathophysiological events
associated with thrombohemorrhagic disorders. 12 Knowledge of these essentials is important for
proper treatment planning and dental management of such patients. Additionally, complex cases of
clotting and bleeding disorders most likely require physician consultation, interpretation of
laboratory testing, and prudent decision making when selecting a dental or hospital treatment site.
Generally, comprehensive assessment of data, including laboratory tests; diagnosis of the condition;
individualized treatment planning with regards to controlling the bleed; and careful manipulation of
tissues during implementation is tantamount to successful management of dental patients with
bleeding disorders. 12

53
 g. Dental management of haematologic disorders – anaemia

Introduction

-Erythrocytes are produced from the bone marrow from pleuripotent stem cells via immature cells
(reticulocytes).
-Reticulocytes retain their organelles and nuclear remnants and still have the ability to divide and
are released into the blood when the demand is high.
-Erythropoietin produced in the kidneys stimulates erythrocytes production when the oxygen level
is low.
-Mature erythrocytes contain only haemoglobin which carry oxygen and carbon dioxide between
the lungs and the tissues.
-Haemoglobin production requires iron, protoporphyrin and globin chains.
-Haemoglobin is a heterogenous group of proteins consisting of 4 globin chains and 4 haem
groups.
-In an adult, the normal haemoglobins are HbA, HbA2 and HbF.

ANAEMIA (Source: Owotade FJ. 18)

-Haemoglobin level lower than what is normal for the age and sex.
-Prepubertal Hb<11 g/dl
-Adult female Hb<11.5 g/dl
-Adult male Hb<13.5 g/dl
-Anaemia impairs the oxygen carrying capacity of the blood, it is not a disease but a manifestation
of many diseases.

Classification of anaemia (Source: Owotade FJ. 18)

-Based on the size of the RBC
-Microcytic anaemia is when the mean corpuscular volume (MCV) is less than 78 fl.
-This is the most common and usually due to iron deficiency.
-Normocytic anaemia is when the RBC size is normal (MCV 79 – 98 fl)
-This is usually due to chronic diseases like leukaemia, liver disease, renal failure and sickle cell
disease.
-Macrocytic anaemia is when the MCV is >99 fl.

54
-Usually arise from vitamine B12 or folate deficiency. Folate and B12 deficiency can arise from
increased demand as in pregnancy or malignancy or as a result of alcoholism.
-Some drugs deplete folate and B12 such as methotrexate.
-Macrocytic anaemia may also arise from liver disease and myxedema
Causes of Anaemia
-Poor intakes of Hematinic: Socioeconomic factors, diet fads;
-Impaired absorption: Small bowel disease;
-Increased demand: Pregnancy, haemolysis;
-Impaired erythropoiesis: Aplastic anaemia, leukeamia, drugs
-Haemolitic anaemias: Sickle cell disease;
-Blood loss (commonest): Menorrhagia, GIT lesion (ulcers, CA), trauma
Clinical features (Source: Owotade FJ. 18)
-Asymptomatic in the early stages.
-Pallor of the conjunctiva, oral mucosa or the skin.
-Tiredness, dyspnoea, tachycardia or murmurs and may worsen angina and heart failure.
General management of anaemia (Source: Owotade FJ. 18)
-Establish the precise nature though lab studies-Hb content, MCV etc.
-Replace Hb with haematinics, blood transfusion of erythropoietin.
-Erythropoietin is indicated in the treatment of anaemia of renal failure and cytotoxic therapy.
Dental aspect of management (Source: Owotade FJ. 18)
-Local anaesthesia is sufficient for pain control.
-Conscious sedation should be used only when oxygen is available to supplement.
-Deep sedation carries the risk of hypoxia.
-Avoid Nitrous oxide (N2O) if vitamin B12 deficiency is suspected. N2O can interfere with B12
metabolism and neurologic function if administered for more than 12 hours.
-Anaemia should be corrected preoperatively if general anaesthesia (GA) is indicated.
-Elective surgery under GA should not be carried out if the Hb is less than 10 g/dl.
-The myocardium may not be able to respond to increased demands for oxygen if adequate
oxygenation is not ensured.
-In an emergency, blood transfusion can be used to correct the anaemia. Diuretics should be
administered to prevent volume overload.
-Some anaemias may cause oral ulcers, glossitis or angular stomatitis and will be discussed with the
specific anaemias.

55
 Deficiency anaemias (Source: Owotade FJ. 18)

1. Iron deficiency anaemia

-Common in this environment due to malnutrition, malaria and chronic blood loss.
-Manifest as impaired exercise capacity and koilonychia.
-Treated with ferrous sulphate 200 mg tds. Ferrous salt is preferable to the ferric salts as they are
better absorbed in the gut.
-Present in the mouth as a sore, physically normal tongue even before haematologic parameters fall
below the normal levels.
-Severe anaemia is a cause of atrophic glossitis.
-Rarely, may be associated with Plummer-Vinson syndrome (glossitis, dysphagia and iron
deficiency anaemia).
-Candidosis may be precipitated or aggravated by anaemia.
-Angular cheilitis may be a feature though this is more commonly due to candidiasis.
-Aphthous stomatitis may also be associated with iron deficiency anaemia.
2. Vitamin B12 deficiency
-In addition to general features of anaemia, this may present with neurologic symptoms of
paraesthesia of the extremities.
-Oral features are similar to Iron def anaemia apart from association with Plummer Vinson
syndrome.
3. Folate (Folic Acid) deficiency
-No body stores and usually due to inadequate intake
-Deficiency in pregnancy associated with cleft deformities
-Sore, physically normal tongue, atrophic glossitis and angular cheilitis are oral features
4. Haemolitic anaemias
-May be due to: Inherited abnormalities of formation (haemoglobinopathies), Inherited abnormal
structure (G6PD deficiency), Damage to erythrocytes (autoimmune, drug induced or infective).
-Increased erythrocyte destruction leads to billirubin overproduction and jaundice.
-Spleen may be enlarged, reticulocyte and uric acid levels will be raised.

56
 DENTAL MANAGEMENT OF SICKLING DISORDERS (Source: Owotade FJ. 18)

-Important to recognize and diagnose the condition.

-For patients with sickle cell disease (HbSS), local anaesthesia (LA) is preferred.
-Avoid prilocaine (may cause methaemoglobinaemia if used excessively).
-Aspirin in large doses may cause acidosis which can precipitate a crisis. Best avoided.
-Conscious sedation and relative analgesia are safe, avoid benzodiazepines which can depress
respiration.
-For treatment under general anaesthesia (GA), correct anaemia preoperatively. Exchange blood
transfusion is occasionally indicated.
-Prophylactic antibiotics should be given for surgical procedures and infections should be treated
aggressively.
Orodental features of SCD include:
-painful infarcts in the jaws which present like and may be construed as toothache.
-dense radiopacities in the jaws and skull-stepladder trabecular pattern.
-Osteomyelitis may occur in the mandible.
-Neuropathies including lip anaesthesia.
-Hypercementosis.
-Bone marrow hypertrophy may lead to enlarged maxilla and increased overjet and overbite.
-Bossing of the skull and hair on end trabecular pattern, tower skull appearance.
-Enamel hypomineralisation and calcified pulp canals. 18

h. Dental Treatment in Patients with Leukemia

According to Deliverska EG, Krasteva A. in the oral cavity local symptoms and findings of
leukemia include paleness of the oral mucosa with gingival bleeding that develops into painless
gingival hyperplasia, petechiae, hemorrhages, and ulcerative necrotic lesions (Fig. 4 and Fig. 5).
Once the diagnosis has been made, consultation with the patient physician or oncologist is
mandatory before commencing dental treatment.
The main problems in dental treatment of patients with hematologic malignancies of white
cells are:
• Bleeding tendency
• Increased risk of infection - odontogenic infections and opportunistic infections:

57
• Risk of developing osteonecrosis of the jaw
• Anemia
• Corticosteroids treatment - may display evidence of secondary adrenal insufficiency.
• Secondary malignancies
The dentist, and mainly the periodontists and oral pathologist, plays a fundamental role in
the early diagnosis of leukemia knowing that the first symptoms of the disease occur in the oral
cavity with normal or show subtle changes in initial laboratory tests. 13

Fig. 4. Gingival hyperplasia, Source: Deliverska EG, Krasteva A. 13

Fig. 5. Initial intra-oral view of the patient with leukemia, Source: Deliverska EG, Krasteva A.
13

58
 6. Dental management of patients with endocrine disorders
According to Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión Pérez M. endocrine
system is responsible for hormonal secretion and is closely related to the central nervous system, as
7
it diversifies its functions through the hypothalamus and pituitary. It controls physiological
processes and maintains homeostasis. The neuroendocrine system is responsible for adaptation to
environmental changes. Also, a function of the nervous system is to provide a correct organic
response. Its response may be primary, with the release of neurotransmitters, or if the stimulus
prevails, the endocrine system secretes hormones. This is especially important in dentistry because
many of the patients attending the dental clinics face stressful situations. Awareness is therefore
necessary of the risks and difficulties that may arise during the dental management of patients with
endocrine disorders and the most common oral manifestations.
Oral manifestations and dental management of patients with thyroid gland disorders The
thyroid gland secretes three hormones: thyroxine (T4), triiodothyronine (T3) and calcitonin. T4 and
T3 are hormones that affect metabolic processes throughout the body and are involved in oxygen
use. Thyroidstimulating hormone (TSH or thyrotropin), produced by the pituitary gland, regulates
the secretion of thyroid hormones (T4 and T3) through a negative feedback mechanism. Calcitonin
is involved, with parathyroid hormone and vitamin D, in regulating serum calcium and phosphorus
levels and in the skeletal remodeling. Thyroid hormones influence the growth and maturation of
tissues, energy metabolism and turnover of both cells and nutrients
The most common diseases are hyperthyroidism, hypothyroidism, diabetes mellitus,
adrenocortical insufficiency, primary hyperparathyroidism, secondary hyperparathyroidism,
hypoparathyroidism, Addison’s disease, hyperadrenocorticism (Cushing’s syndrome).
a. Hyperthyroidism
According to Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión Pérez M. hyperthyroidism
or thyrotoxicosis is defined by a decrease in thyroid hormone production and thyroid gland
function. 7 It is caused by ectopic thyroid tissue, toxic thyroid adenoma, toxic multinodular goiter,
subacute thyroiditis, factitious thyrotoxicosis and Graves’ disease and diffuse toxic goiter, being the
most common cause of hyperthyroidism. Hyperthyroidism can have clinical manifestations at
gastrointestinal levels (weight loss, increased appetite, nausea and vomiting), in hair, skin and nails
(thin and brittle hair, soft nails, warm and moist skin, increased skin pigmentation and heat
intolerance). In the hands (palmar erythema, fine tremor, sweating and clubbing). At neuromuscular
levels (fatigue, atrophy, weakness, muscle fatigue and pain). At cardiovascular levels (tachycardia,
palpitations, systolic hypertension and dyspnea). At psychological levels (anxiety, nervousness,

59
irritability, insomnia, impaired concentration and reduced stress threshold) and in ocular level
(bilateral exophthalmos, ptosis, periorbital edema, retraction of the upper and lower eyelid due to
muscle contracture and conjunctival injection).
Oral manifestations are accelerated dental eruption in children, maxillary or mandibular
osteoporosis, enlargement of extraglandular thyroid tissue (mainly in lateral posterior tongue),
increased susceptibility to caries and periodontal disease (possibly because these patients feel the
need to consume higher quantities of sugar to meet their physical requirements), burning mouth
syndrome and development of connective-tissue diseases such as Sjögren’s syndrome or systemic
lupus erythematosus. Treatment of patients with thyrotoxicosis may involve antithyroid agents
(propylthiouracil, carbimazole, and methimazole) which block hormone synthesis; iopanoic acid
and ipodate sodium that are inhibitors of the peripheral conversion of T4 to T3; beta-blockers
(propanolol) that slow the adrenergic activity and eliminate the tachycardia, anxiety, nervousness,
tremors and sweating; glucocorticosteroids, such as dexamethasone, that decrease the secretion of
thyroid hormone and iodine that inhibits the release of preformed hormone. (Table 16).
Dental management of the patient with hyperthyroidism (Source: Carlos Fabue L,
Jiménez Soriano Y, Gracia Sarrión Pérez M. 7 ):
1. In controlled patients, should carry out the same dental management as in healthy patients
and avoid severe stress situations and the spread of infectious foci.
2. In uncontrolled cases, the dentist must take the same precautionary measures as in
controlled patients, restrict the use of epinephrine or other pressor amines in local
anesthetics of the retraction cords because the myocardium of these patients is sensitive to
adrenaline and may unleash arrhythmias, palpitations and chest pain. The dentist must avoid
surgical procedures because surgery, presence of acute oral infection and severe stress may
precipitate thyroid storm crisis. If an emergency dental treatment is required, consultation
with the patient’s endocrinologist is advisable because a conservative treatment is often
preferable. Treatment should be discontinued if signs or symptoms of a thyrotoxic crisis
develop, and access to emergency medical services should be available. These symptoms
include tachycardia, irregular pulse, sweating, hypertension, tremor, nausea, vomiting,
abdominal pain and coma.
3. People who have hyperthyroidism and are treated with propylthiouracil must be monitored
for possible agranulocytosis, hypoproteinemia or bleeding, and a complete blood count
including prothrombin time before performing any invasive procedures is usually
recommended.

60
 4. These patients are susceptible to central nervous system depressant drugs such as
barbiturates.
5. In these patients proper analgesia is indicated and nonsteroidal anti-inflammatory drugs
(NSAIDs) and aspirin should be used with caution.

b. Hypothyroidism
According to Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión Pérez M. hypothyroidism
7
is defined by a deficiency of the thyroid hormone. It can be acquired or by congenital defects.
When it is present in infancy, it is manifested as cretinism and if it occurs in adults (especially in
middle-aged women) it is known as myxedema. Characteristic signs of cretinism include mental
retardation, developmental and growth delay, marked disproportion between the head and body
(wide head), lack of muscle tone, overweight, less expressive face with a broad and flat nose,
hypertelorism, short neck and thick, pale, dry and wrinkled skin. Myxedema is characterized by
widespread metabolic slow-down, depression, overweight, diminished cardiac output and
respiratory rate, decreased pulse, generalized edema (especially in face and extremities), hoarseness
because the edema affects to vocal cords, sinus bradycardia, swollen nose, ears and lips, thickened
7
and dry skin, scalp brittleness, thin or absent eyebrows and decreased sweating. According to
Atanasov D. another symptoms are: fainting, constipation, headache, arthritis, different menstrual
3
disorders. Generalized edema can affect the tongue causing difficulty speaking and swallowing
and serrated tongue. Common oral findings in hypothyroidism include: delayed tooth eruption,
enamel hypoplasia in both dentitions, being less intense in the permanent dentition, micrognathia,
open bite due to lack of condylar and mandibular growth, macroglossia, thick lips, dysgeusia and
mouth breathing. (Table 16). Patients with hypothyroidism are treated with synthetic preparations
containing sodium liothyronine, sodium levothyroixin or 1-throixine. Hormone replacement therapy
based on thyroid hormones can be prescribed in cases of severe deficiency of thyroid hormones.
Dental management of the patient with hypothyroidism (Source: Carlos Fabue L,
Jiménez Soriano Y, Gracia Sarrión Pérez M. 7)
Consulting the patients’ physician and carrying out a detailed general clinical history before
performing dental treatment is indicated.
1. In controlled patients should be avoided oral infection.
2. In uncontrolled patients, oral infection, central nervous depressants such as narcotics and
barbiturates should be avoided because they may cause an exaggerated response. In
controlled patients, these drugs should be used sparingly, with a reduced dosage. The

61
 presence of oral infection, central nervous depressants and surgical procedures can
precipitate a myxedematous coma. Surgery procedures should also be avoided in these
patients. Myxedematous coma includes hypothermia, bradycardia, severe hypotension and
epileptic seizure. If that happens, dental treatment should be discontinued and access to
emergency medical services should be available
3. Drug interactions of 1-thyroxine include: Metabolism increase using phenytoin, rifampin
and carbamazepine; Absorption is impaired when iron sulfate, sucralfate and aluminum
hydroxide are used; Concomitant use of tricyclic antidepressants elevates 1-thyroxine levels.
4. These patients are susceptible to cardiovascular disease, therefore they may be on
anticoagulation therapy. Before dental treatment is carried out, a complete blood count is
required to evaluate coagulation factors; should be avoided the use of epinephrine in local
anesthetics or retraction cords. Antibiotic prophylaxis must be assessed in valvular
pathology and atrial fibrillation.

HYPERTHYROIDISM HYPOTHYROIDISM
1. Accelerated dental eruption in children 1. Delayed eruption
2. Maxillary or mandibular osteoporosis 2. Enamel hypoplasia in both dentitions, (being
less intense in the permanent dentition)
3. Enlargement of extraglandular thyroid tissue 3. Anterior open bite
(mainly in the lateral posterior tongue)
4. Increased susceptibility to caries 4. Macroglossia
5. Periodontal disease 5. Micrognathia
6. Burning mouth syndrome 6. Thick lips
7. Development of connective-tissue diseases 7. Dysgeusia
like Sjögren’s syndrom or systemic lupus
erythematosus
8. Mouth breathing
Table 16. Oral manifestations of patients with thyroid gland disorders, Source: Carlos Fabue
L, Jiménez Soriano Y, Gracia Sarrión Pérez M. 7

Oral manifestations and dental management of patients with parathyroid glands disorders
Parathyroid glands secret parathyroid hormone (PTH) involved in regulating the metabolism of

62
calcium and phosphorus. PTH plays an important role in tooth development and bone
mineralization and increases bone resorption. In the kidneys, it stimulates formation of active
metabolite of vitamin D, which promotes the intestinal absorption of calcium and decreases renal
reabsorption of phosphate.

c. Hyperparathyroidism (Source: Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión

Pérez M. 7)
Hyperparathyroidism (HPT) is characterized by hypersecretion of parathyroid hormone
which occurs in three categories (8-11):
− Primary: occurs with a hyperfunction of one or more parathyroids, usually caused by a
tumour (adenoma in 85% of all cases) or hyperplasia of the gland that produces an increase
in PTH secretion resulting in hypercalcemia and hypophosthamia.
− Secondary: normally related to patients with intestinal malabsorption syndrome or chronic
renal failure, occurring in a decrease of vitamin D production or with hypocalcemia causing
the glands to produce a high quantity of PTH. There is also hyperphosphatemia. The PTH-
related signs are brown tumors and osteitis fibrosa cystica, which is referred as renal
osteodystrophy or Von Recklinghausen’s disease.
− Tertiary: is an uncommon condition, affecting up to 8 % of patients with secondary HPT
after a successful renal transplant. It occurs when the parathyroids activity becomes
autonomous and excessive, leading to hypercalcemia.

The diagnosis of HPT is suspected by an increase in serum calcium and it is confirmed by

the increase in PTH. One of the main clinical manifestations of hyperparathyroidism is bone
disease. The ribs, clavicles, pelvic girdle and mandible are the bones most involved. In the oral
cavity, the most common clinical manifestations of HPT are brown tumor, loss of bone density,
weak teeth, malocclusions, soft tissue calcifications and dental abnormalities such development
defects, alterations in dental eruption and widened pulp chambers. (Table 17). Brown tumor
presents itself as a friable red-brown mass. Its name is due to color that it takes from the
haemorrhagic infiltrates and haemosiderin deposits that are often found inside. Brown tumor
presents as osteolytic lesion that develops due to changes in bone metabolism caused by high serum
concentration of PTH. It is mainly due to secondary HPT in patients with renal insufficiency, but it
has also been described as a rare manifestation of calcium malabsorption and some forms of
osteomalacia. Nowadays, brown tumor is an extremely rare manifestation of primary HPT; in these

63
cases it is usually a result of the overproduction of the parathyroid hormone by a parathyroid tumor
(single adenoma, 2 or more adenomas or carcinoma). Mandible involvement is common, especially
in the area of premolars and molars, and it is rare in maxilla.

HYPERPARATHYROIDISM HYPOPARATHYROIDISM
1. Dental abnormalities: 1. Dental abnormalities:
- Widened pulp chambers - Enamel hypoplasia in horizontal lines
- Development defects - Poorly calcified dentin
- Alterations in dental eruption - Widened pulp chambers
- Weak teeth - Dental pulp calcifications
- Maloclussions - Shortened roots
- Hypodontia
- Delay or cessation of dental development
2. Brown tumor 2. Mandibular tori
3. Loss of bone density 3. Chronic candidiasis
4. Soft tissue calcifications 4. Paresthesia of the tongue or lips
5. Alteration in facial muscles

Table 17. Oral manifestations of patient with parathyroid gland disorders, Source: Carlos
Fabue L, Jiménez Soriano Y, Gracia Sarrión Pérez M. 7

Radiographically, lesions are characterized as well-defined radiolucent areas, uni or

multilocular. As characteristic radiographic findings can be found a widespread loss of the lamina
dura, and changes in the pattern of the trabecular bone of the jaws. Long-term injures commonly
produce a significant expansion of cortical, root resorption and displacement of roots can appear.
Histologically, it is characterized by an abundant estroma, consisting of bundles of spindle or oval
cells, and several multinucleated osteoclast-like giant cells. Calcified material can be found, as well
as areas with extravastion of red blood cells and pigmentation by haemosiderin. These findings are
not pathognomonic, making it necessary to perform a differential diagnosis with other lesions such
as an aneurismal bone cyst, cherubism and central giant cell granuloma; being the presence of this
lesion together with a history of HPT which confirms the diagnosis of brown tumor. The treatment
of HPT is the first step in the management of the brown tumor, as spontaneous regression of the
lesion often occurs. However, several cases of brown tumor that did not disappear or even grew
after normalization of HPT level have been reported. In these cases brown tumor resection should
be the preferred treatment.

64
 Dental management of the patient with hyperparathyroidism
The clinical management of these patients does not require any special consideration. We
should know that there is a higher risk of bone fracture, so we must take precaution in surgical
treatments. On the other hand, it is important to recognize the presence of brown tumour and to
perform a correct differential diagnosis so as not to conduct an inadequate treatment.
d. Hypoparathyroidism (Source: Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión
Pérez M. 7)
Hypoparathyroidism is a metabolic disorder characterized by hypocalcemia and
hypophosphatemia due to a deficiency or absence of parathyroid hormone secretion. It may also
develop as an isolated entity of unknown etiology (idiopathic hypoparathyroidism), or in
combination with other disorders such as autoimmune diseases or developmental defects.
Hypoparathyroidism can cause hypocalcemia with consequent paresthesias, tetany and seizures.
Disorders of ectodermal tissues are also common in these patients. These disorders include
alopecia, scaling of the skin, deformities of the nails and dental abnormalities such as enamel
hypoplasia in horizontal lines, poorly calcified dentin, widened pulp chambers, dental pulp
calcifications, shortened roots , hypodontia and mandibular tori as PTH affects rate of eruption,
formation of the matrix and calcification. A delay or cessation of dental growth and development,
chronic candidiasis of the oral mucosa and nail, paresthesia of the tongue or lips and alteration of
the facial muscles can occur. (Table 17).
This pathology is diagnosed on the basis of measurements of serum calcium and parathyroid
hormone levels. The main treatments available for these patients is vitamin D or its analogues,
calcium salts and drugs that increase renal tubular resorption of calcium, to obtain adequate, but
low, normal serum calcium levels.
Dental management of the patient with hypoparathyroidism (Source: Carlos Fabue L,
Jiménez Soriano Y, Gracia Sarrión Pérez M. 7)
These patients have more susceptibility to caries because of dental anomalies. Dental
management will be the prevention of caries with periodic reviews, advice regarding diet and oral
hygiene instructions. Before performing dental treatment, serum calcium levels should be
determined. They must be above 8mg/100ml to prevent cardiac arrhythmias, seizures,
laryngospasms or bronchospasms.
Oral manifestations and dental management of the patient with adrenal glands disorders
(Source: Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión Pérez M. 7): The adrenal glands are
located on the upper pole of each kidney. They are composed of an internal or core portion (the

65
adrenal medulla), which produce adrenaline, noradrenaline, dopamine and progesterone; and an
outer portion or cortex, which is in turn responsible for the production of steroid hormones, such as:
glucocorticoids (cortisol and cortisone), mineralocorticoids (aldosterone and 18-
deoxycorticosterone), and androgens (dehydroepiandrosterone). The cortex has three layers:
glomerular or external, where mineralocorticoids are released, the fascicular or intermediate, where
glucocorticoids are produced and reticular or internal where androgens are secreted. Regarding the
role of substances that are secreted by the cortex, cortisol is involved in the mechanisms of
adaptation of the organism to stress maintaining homeostasis; it has anti-inflammatory and
immunosuppressive effect, it is responsible for mobilizing fatty acids from adipose tissue, it
maintains vascular reactivity, it promotes the liver’s protein synthesis via neoglycogenesis, it
increases gycemia, it inhibits bone formation and delays healing. Corticosteroid production and
release from the adrenal cortex is in turn regulated by adrenocorticotropic hormone (ACTH), which
is synthesized and secreted in the anterior hypophysis (adenohypophysis). In accordance to the
circulating glucocorticoid concentrations, a selfregulating or negative feedback mechanism is
established at hypothalamic and hypophyseal level. ACTH is in turn controlled by a series of factors
such as corticotropin release hormone (CRH), which is secreted by the hypothalamus, and by
circadian rhythms (waking-sleep cycle), with cyclic variations in the plasma cortisol concentrations
in the course of the 24-hour day, being maximum early in the morning and minimum at evening.
Basal cortisol secretion in turn gradually increases with age, and an association moreover exists
between high basal cortisol concentrations and a reduction in specific cognitive functions.
Aldosterone is necessary for maintaining sodium and extracellular fluid balance, resulting in
resorption of sodium in exchange with the potasium and hydrogen ions in the distal tubule of the
nephron and in other tissues such as salivary glands and colon. It makes up to renin-angiotensin-
aldosterone axis. Kidneys, in response to low blood volume, real or perceived (heart failure), secrete
an enzyme called rennin, which acts in the general circulation on angiotensinogen produced by the
liver and converts it into angiotensin I. Angiotensin I, under the action of the angiotensin converting
enzyme (ACE), converts it in angiotensin II. Angiotensin II is a potent arteriolar vasoconstrictor and
the primary regulator of aldosterone secretion, which maintains blood volume by retaining sodium.

e. Addison’s disease (Source: Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión Pérez M.
7
)
In Addison’s disease or primary adrenal insufficiency exists a deficiency in the secretion of
glucocorticoid and mineralocorticoid hormones by the adrenal cortex. It is associated with

66
idiopathic, surgical, or infectious destruction or tumor of parenchyma of the adrenal gland or
infiltration of the cortex by sarcoidosis, tuberculosis or amyloidosis. Cortisol deficiency clinically
manifests as hypoglycemia, hypotension, asthenia, muscle weakness, anorexia, nausea, weight loss
and diminished resistance to infections and stress. Characteristic melanic pigmentation may develop
as a consequence of cessation of inhibition at hypophyseal level, with simultaneous increments of
both ACTH and melanocyte stimulating hormone (MSH). When this happens, the skin darkens in
regions such as the elbows, folds of the hands or areolas of the breasts. The oral mucosa can in turn
develop black-bluish plaques, mainly affecting buccal mucosa but it can also be seen on the gums,
palate, tongue and lips. The lack of aldosterone leads to sodium and liquid depletion with increased
diuresis and secondary dehydration and hypotension.
Dental management of the patient with Addison’s disease (Source: Carlos Fabue L,
Jiménez Soriano Y, Gracia Sarrión Pérez M. 7)
Most of these patients are treated with corticosteroids and can be distinguished different
stages of adrenal suppression, especially in patients undergoing corticosteroid therapy:
− Stage I: doses of corticosteroids do not produce adrenal suppression.
− Stage II: the glucocorticois in blood inhibit the hypotalamic-hypophyseal-adrenal axis, and
the body stops producing cortisol physiologically. This stage is therefore characterized by
adrenocortical suppression, though the administered corticoid dose is still insufficient to
cover the organic needs in the event of stressinducing situations.
− Stage III: the administered corticoid dose is sufficiently high to continue suppressing the
adrenal cortex but also to cover the body needs in the event of stress. This is interesting
when we perform dental treatment because according to the stage in which the patient is,
supplementation of corticosteroids may or not be necessary:
-Patients with low-dose corticotherapy (LDC) (< 30mg of hydrocortisone/day):
1. Patients with a history of regular corticoid use: no supplementing is required either for
routine procedures, nor surgical treatments because with this dose of corticosteroid, adrenal
suppresion does not occur.
2. Patients presently using corticoids: no supplementing required.
-Patients with high-dose corticotherapy (HDC) (> 40 mg of hydrocortisone/day):
1. Patient with a history of regular use of HDC for short periods (less than one month): the
adrenal suppression is transient, recovering the stress response within 14 days after cessation
of steroids. Therefore, for routine dental procedures, surgical procedures, very extensive
treatments and in highly anxious patients we must consider: Those who have discontinued

67
 corticosteroid treatment less than 14 days ago will require a daily maintenance dose on the
day of treatment. If more than 14 days: no supplementing will be required.
2. Patients with a history of regular use of HDC for more than one month: no established
regimen.
3. Patients presently using HDC for one month or more: no supplementing required.
-Patients presently using 30-40 mg of hydrocortisone/ day: If the patient is highly anxious or
lengthy dental treatment or surgery procedure is to be performed, the daily dose should be doubled
on the day of treatment. If postoperative pain is expected, should also double the daily dose on the
first postoperative day.
-Patients receiving corticotherapy on alternate days for at least 30 days: On the non-corticoid days,
no supplementing is required. Conservative management is indicated on the rest of the days.
-Patients with topical or inhaled steroids: no supplementing required.
Other aspects of dental management of these patients are:
1. Conducting treatment in the morning.
2. Control of anxiety and emotional stress.
3. Use long-acting anesthetics.
4. Treatment of postoperative pain.
5. Prevention of iatrogenic fracture during surgery in patients with a long history of continuous
corticotherapy, because glucocorticoids can increase the risk of fracture by causing
osteoporosis.
6. Consideration is also required of the possible interactions of glucocorticoids with a other
drugs:
− Phenytoin, barbiturates and rifampicin accelerate glucocorticoid metabolism.
− Prednisone bioavailability decreases with the administration of antacids.
− Glucocorticoids increase the requirements of insuline, oral antidiabetic drugs and
hypotensive medication.

f. Addisonian crises (Source: Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión Pérez M.
7
)
Addisonian crises or acute adrenocortical insufficiency is a rare but serious complication in
patients with primary Addison’s disease. Although, actually it is more likely to be attributable to
secondary adrenal failure (administration of high-doses of exogenous corticosteroids
therapeutically) than to Addison’s disease. The reason for this is the sudden withdrawal of

68
exogenous corticoids, or the existence of situations requiring greater amounts of corticoids than
those afforded by replacement therapy. It presents as a sudden failure of the adrenal cortex function.
The resulting clinical picture compromises shock with nausea, vomiting, abdominal pain and
hypotension. Fever and hypothermia may be observed and can lead to coma and death. 7
According to Ugrinov R. another reasons for addisonian crises are chronic adrenocortical
insufficiency a background on increased requirements: surgical interventions, intercurrent
infections, intoxications, physic and psychic tension etc. 20
Dental management of the patient with Addisonian crises (Source: Carlos Fabue L,
Jiménez Soriano Y, Gracia Sarrión Pérez M. 7)
Prevention is the best management approach for Addisonian crises - with a detailed clinical
history and a consultation with the specialist is recommended, and take action accordingly.
However, if crisis takes place, the dentist should interrupt dental procedure, place the patient in
dorsal decubitus and contact with the corresponding medical emergency service. Until medical help
arrives, the patient should be administered oxygen (5-10 liters/min). If the patient is unconscious, he
should be placed in dorsal decubitus with the legs raised, and should notify the emergency service
to arrange transfer of the patient to the hospital. Before four minutes have elapsed, basic vital
support should be provided in accordance to the patient’s condition. If an adrenal cause is
suspected, 100 mg of hydrocortisone should be administered intravenously or intramuscularly,
within 30 seconds if possible, and two hours later, another 100 mg of hydrocortisone dissolved in
saline for intravenous or intramuscular injection should be provided.

g. Hyperadrenocorticism (Cushing’s syndrome), Source: Carlos Fabue L, Jiménez

Soriano Y, Gracia Sarrión Pérez M. 7
Cushing’s syndrome (CS) refers to manifestations induced by chronic exposure to excess
glucocorticoids produced by the adrenal cortex. This excess can be caused by various reasons. It
most commonly arises from iatrogenic causes (due to administration of exogenous glucocorticoids).
The second most common cause is a high production of ACTH as a result, in most cases, of the
presence of a pituitary corticotroph adenoma or less frequently by an extrapituitary tumor or very
rarely by a tumor secreting CRH. CS is suspected in the presence of central obesity with
supraclavicular fat accumulation and a cervical fat pad, moon face, thinned skin, acne and
hirsutism. Hypertension, glucose intolerance, menstrual irregularity, osteoporosis and pathological
fractures, delayed healing, increased risk of infection and neuropsychological disturbances

69
including depression, emotional irritability, sleep disturbances and cognitive deficits are also
observed. Purple striae and muscular atrophy are particularly positive stigmata in adults, whereas in
child growth retardation are frequently present.
Dental management of the patient with hyperadrenocorticism
Dental management in these patients consists in prevention of infections, pathological
fractures during surgical treatments and complications such as hypertension, hyperglycemia,
depression and delayed healing. In patients on steroids we must evaluate the need to administer
additional corticosteroids. 7

h. Dental management of patients with diabetes mellitus (Source: Vernillo AT. 21)
Diabetes mellitus, a complex metabolic disorder, is a syndrome characterized by
abnormalities in carbohydrate, lipid, and protein metabolism that results either from a profound or
an absolute deficiency of insulin (type 1) or from target tissue resistance to its cellular metabolic
effects (type 2). A third type of diabetes mellitus, gestational diabetes, represents carbohydrate
intolerance with its onset or first recognition during pregnancy. There is no definitive cure for
diabetes mellitus. The most common endocrine metabolic disorder, it affects an estimated 14
million people in the United States, with the incidence of new cases increasing by more than
700,000 cases per year. An additional estimated 7 million people have diabetes mellitus and do not
know it because it has not yet been diagnosed. Without a proper diagnosis, these individuals are at
significant risk for life-threatening complications. In some cases, these patients are diagnosed with
diabetes only when they arrive at an emergency department with severe hyperglycemia (diabetic
coma).
Diabetes mellitus is also a pernicious disease. It is the third leading cause of mortality and
morbidity in the United States, accounting for about 40,000 deaths per year. The relative risk for
persons with diabetes acquiring end-stage renal disease is 25 times that of persons without diabetes.
The relative risk for diabetic patients having a limb amputated because of diabetic complications is
over 40 times that of normal. More than 20,000 amputations per year are performed on patients with
diabetes mellitus, representing nearly 50% of all nontraumatic amputations. The relative risk of an
individual with diabetes becoming blind is 20 times greater than that of other individuals.
Myocardial infarction is 10 times more likely in the diabetic patient. Types 1 and 2 diabetes mellitus
represent the largest category of diabetic patients. Therefore, this section will focus on these two
types and discuss concepts of their etiology, pathogenesis, and complications.
Type 1 diabetes mellitus (Source: Vernillo AT. 21)
Hyperglycemia is a hallmark of diabetes mellitus—as are its chronic metabolic

70
complications. The chronic metabolic complications are generally more severe in the person with
type 1 diabetes. These include increased susceptibility to infection and delayed healing, neuropathy,
retinopathy, and nephropathy (microvascular disease); accelerated atherosclerosis with associated
myocardial infarction, stroke, atherosclerotic aneurysms (macrovascular disease), and amputation.
The development of secondary lesions in the diabetic patient relates largely to the severity and the
duration of hyperglycemia. In general, the major classic findings of hyperglycemia—polyuria,
polydipsia, polyphagia, weight loss, and fatigue—occur in the setting of new-onset diabetes in
young patients whose disease is caused by profound insulin deficiency (type 1). Type 1 diabetes, or
insulin-dependent diabetes mellitus (IDDM), constitutes approximately 3% to 5% of all cases of
diabetes mellitus and is related to autoimmune-mediated destruction of the insulin-producing
pancreatic islet beta cells. Thus, these patients are prone to ketoacidosis, an acute and potentially
life-threatening metabolic complication, and are completely dependent on exogenous insulin to
sustain life. Ketoacidosis can develop rapidly and lower the pH of the blood, leading to coma and
death. The onset of signs and symptoms in these patients is relatively abrupt and usually occurs at a
young age (mean, 15 years), although IDDM can arise at any age.
The destruction of the beta cells in the type 1 diabetic has been linked to the presence of certain
major histocompatibility locus antigens (HLA), some of which are also associated with other
autoimmune diseases. In fact, the only genes definitely associated with type 1 diabetes are those of
the major HLA. Ninety-five percent of persons with type 1 diabetes, compared with 40% of the
general population, express either HLA-DR3 or HLA-DR4, or both. Thus, one must take into
careful consideration the potential for the development of other autoimmune-mediated endocrine
diseases characterized by hypofunction when assessing the overall clinical management of the
person with type 1 diabetes.
Type 2 diabetes mellitus (Source: Vernillo AT. 21)
Type 2 diabetes mellitus, or non–insulin-dependent diabetes mellitus (NIDDM), accounts for
approximately 95% of all cases of diabetes. The insulin levels of affected patients may be normal,
increased, or decreased, but there is no profound insulin deficiency. However, over many years, the
majority of persons with type 2 diabetes show a continual decrease in their insulin levels. The
etiology and pathogenesis of type 2 diabetes may be more heterogeneous with multiple biochemical
or molecular lesions. These defects may include impaired insulin secretion; a defect at the insulin
receptor; or shown more recently, a defect distal to the insulin receptor; and a defect in the hepatic
uptake of glucose contributing to insulin intolerance. These patients are not prone to ketoacidosis
under basal conditions and are not completely dependent on exogenous insulin to sustain life.
However, insulin treatment for patients with NIDDM (25%-30% of cases) can improve the control

71
of hyperglycemia.
The hyperglycemia in NIDDM is not caused by autoimmune destruction of beta cells, but it is
rather a failure of those cells to meet an increased demand for insulin (impaired insulin secretion).
Obesity is an overwhelming risk factor and is frequently associated with NIDDM. Obesity and its
associated high serum cholesterol levels can also exacerbate accelerated atherosclerosis, which is
frequently a preexisting component of clinical diabetes. Diabetes develops more commonly in
persons with shoulder girdle obesity or truncal obesity. The diagnosis of type 2 diabetes usually
occurs after a person reaches 40 years of age, when the basal metabolic rate declines and the body
weight increases. However, a recent increasing trend in type 2 diabetes is now seen in teenagers and
in the 20-year-old age group; this disturbing trend may be related to dietary obesity. Eighty percent
of adult diabetics are obese or have a history of obesity. Among adults who are at least 25% over
their ideal body weight, 1 of 5 has elevated fasting blood sugar levels, and 3 of 5 have abnormal
oral glucose tolerance test results. Obesity increases insulin levels and decreases the concentration
of insulin receptors in terms of their sensitivity in tissue (clinical insulin resistance). Exercise
increases the number of insulin receptors and improves insulin sensitivity, whereas a sedentary
lifestyle is associated with glucose intolerance. Regular exercise with weight loss is associated with
a decreased incidence of NIDDM after adjusting for the body mass index.
Multifactorial inheritance also contributes clinically to the development of type 2 diabetes.
However, a family history of diabetes is not a prerequisite for the development of the disease. It
develops in persons with no known family history of diabetes. Still, there is usually a stronger
family history in type 2 than in type 1 diabetes mellitus. Sixty percent of type 2 patients have either
a parent or a sibling with the disease. In some populations—notably the Pima Indians of Arizona
and the natives of Nauru in the Gilbert Islands of the Pacific—a third to a half of all persons are
afflicted with type 2 diabetes. When one member of a monozygotic twinship has the disease, the
second twin is almost invariably affected. However, there is no association with genes of the major
HLA similar to that occurring in type 1 diabetes. Despite the high familial prevalence of type 2
diabetes, the precise mode of inheritance remains undefined.
Medical management, Screening and diagnostic tests: According to Vernillo AT. in 1979,
the National Diabetes Data Group published criteria for the diagnosis of diabetes, criteria that have
become widely accepted as the gold standard for the diagnosis of diabetes mellitus. By these
criteria, at least one of the following conditions must exist to establish the diagnosis of diabetes in
the nonpregnant adult 21:
1. Presence of the classic symptoms of diabetes (polyuria, polydipsia, polyphagia), with

72
unequivocal glycemia (random plasma glucose >200 mg/dL);
2. Fasting plasma glucose >140 mg/dL, or fasting venous (or capillary) whole blood glucose >120
mg/dL on more than one occasion; or
3. Abnormal oral glucose tolerance test result, with test performed under standardized conditions
(75-g glucose load, with blood measurements performed every 30 minutes for 2 hours). Both the 2-
hour level and at least one other sample must exceed 200 mg/dL.
Type 1 diabetes mellitus (Source: Vernillo AT. 21)
Exogenous insulin is administered by subcutaneous injection. Insulin (U-100) is classified as
rapid (insulin lispro [Humalog] and Regular), intermediate (insulin [NPH and Lente]), and long-
acting (insulin [Ultralente]). These different types of insulin vary in their onset, peak, and duration
of activity. The major disadvantage of the intermediate and long-acting insulin is the lack of
consistent predictability, owing to the fact that these preparations are suspensions. It is therefore
important for the patient to mix the suspensions carefully (by slowly rotating the insulin vial) before
injection. A recently developed long-acting, suspension-free insulin (glargine; Lantus) comparable
to NPH insulin activity will soon be available. It should provide improved predictability.
Types of insulin (Source: Vernillo AT. 21)
Lispro and regular insulin are generally taken close to mealtime to match the peak activity of
the injected insulin with the peak absorption of glucose from the small intestine into the
bloodstream. Humalog is the most rapidly acting insulin. It is administered 5 to 15 minutes before a
meal and has a peak activity of 30 to 90 minutes. Therefore, patients must avoid delaying a meal by
more than 45 minutes if taking Humalog. Otherwise, they may rapidly progress to severe
hypoglycemia (insulin shock). Ultralente insulin simulates the basal metabolic rate of insulin
secreted from a normally functioning pancreas. It is “peakless” insulin because of its slow onset,
minimal peak activity, and long duration of action. Intermediate-acting insulin, such as NPH and
Lente, has a slower onset (2 to 4 hours) and peak (4 to 12 hours) activity than rapidly acting insulin.
Thus, NPH or Lente insulin injected at 8 AM will usually enter its peak at noon. It is essential that
the clinician be fully knowledgeable about the peak activity and duration of these different types of
insulin. Severe hypoglycemia (insulin shock) is a life-threatening medical emergency and is far
more common during multiple insulin injections associated with intensive insulin regimens.
Insulin injection regimens (Source: Vernillo AT. 21)
Conventional insulin injection regimens may include 1 daily injection of either NPH or
Lente insulin or 1 injection of either NPH or Lente insulin mixed with more rapidly acting Humalog
or regular insulin. These regimens are not as effective as the intensive insulin regimens in terms of

73
obtaining tight metabolic control, and the number of injections is more limited and leads to wider
fluctuations in blood glucose levels.
An advance that is gaining wider use in the medical management of type 1 diabetes is the insulin
pump. The pump uses only one rapid-acting insulin and therefore eliminates the variability of the
intensive insulin regimen. Pump therapy reduced the incidence of severe hypoglycemia in a number
of studies, with a 6-fold reduction in incidence over that of multiple daily injections in the intensive
regimen. Nonetheless, pump therapy (if not carefully monitored) can lead to rapid hyperglycemia
and ketoacidosis, a life-threatening emergency.
Type 2 diabetes mellitus (Source: Vernillo AT. 21)
Diet modification for weight loss with the corresponding reduction of insulin resistance, as
well as oral agents, are the main therapy for NIDDM. Weight loss enhances the sensitivity of
peripheral insulin receptors to endogenous insulin and reduces the requirements for administered
insulin. Thus, most persons with type 2 diabetes can control hyperglycemia by maintaining an ideal
body weight. However, such weight reduction is often a difficult goal to sustain, requiring a
permanent restriction in caloric intake. Indeed, the most common cause of death for patients with
NIDDM is myocardial infarction and coronary artery disease, which are often related to obesity.
Drug therapy is indicated in medical management when maintaining the ideal body weight fails to
control blood sugar or to ameliorate the symptoms, or when the patient is unable to lose weight or
ketosis is present. Drug therapy includes oral agents and insulin. An increasing number of type 2
patients inject exogenous insulin to improve their glycemic control. Although the administration of
exogenous insulin to a patient with clinical insulin resistance seems paradoxical, the insulin can
improve glucose control. A wide range of oral agents to treat NIDDM exist, including α-glucosidase
inhibitors (acarbose); insulin sensitizers (biguanides, such as metformin, and thiazolidinedones,
such as rosiglitazone); insulin secretagogues (sulfonylureas, first- and second-generation agents);
and benzoic acid derivatives (meglitindes such as repaglinide). These oral agents are of no value in
the treatment of type 1 diabetes mellitus.
At the outset of treating a patient, it is important to recognize that some oral agents do promote
hypoglycemia; in certain instances, this may become severe. Although severe hypoglycemic
reactions are less likely with the oral agents than with insulin, the duration of some of these agents
and their hypoglycemic effect can extend to 24 hours. Sulfonylureas act primarily by stimulating
the pancreatic beta cells to increase insulin production. If food intake is insufficient to elevate blood
glucose levels adequately, a relative excess of plasma insulin may occur, resulting in hypoglycemia.
The α-glucosidase inhibitors, like acarbose, block the proximal absorption of carbohydrate in the
small intestine and pose an interesting dilemma. In combination with sulfonylureas or insulin, the α-

74
glucosidase inhibitors can cause hypoglycemia. However, this hypoglycemia is not typically
reversible with sucrose (candy or table sugar), a disaccharide, because α-glucosidase inhibitors slow
the conversion rate of disaccharides into free monosaccharide glucose units. Thus, only glucose
tablets will rapidly and effectively reverse α-glucosidase—induced hypoglycemia. In contrast,
metformin does not raise insulin levels and rarely causes hypoglycemia. Thiazolidin-edones
increase tissue sensitivity to insulin, especially in muscle; this effect counters the clinical insulin
resistance common in NIDDM. Hypoglycemia is also rarely associated with thiazolidinedones.
Angiotensin-converting enzyme inhibitors: prophylaxis and reduction of diabetic complications
A recent remarkable study found that the angiotensin-converting enzyme (ACE) inhibitor ramipril
may reduce not only cardiovascular events but also the incidence of diabetes-related complications
and even the incidence of diabetes itself. Although ACE inhibitor is a standard antihypertension
drug, its use to reduce or even prevent diabetic complications adds another dimension to treatment.
Thus, an increasing number of diabetic patients are taking ACE inhibitor drugs, even in the absence
of hypertension. However, the dentist must be aware that ACE inhibitor drugs can cause sudden
swelling of the face, lips, tongue, and laryngeal tissues, as well as potential asphyxiation at any
time. Such a life-threatening emergency requires the administration of epinephrine (1:1000) to
reduce the tissue swelling.
Medical management of diabetic emergencies (Source: Vernillo AT. 21)
Dental practitioners should encourage diabetic patients who self-monitor blood glucose
levels to bring their glucometer to the dental office at each visit. The dentist should also purchase a
glucometer and make it available to diabetic patients. Patients can check their blood glucose levels
within 1 minute of the beginning of the dental appointment. If glucose levels are at or below the
lower end of the normal fasting range (80 to 120 mg/dL), then it may be necessary for the patient to
consume a fast-acting carbohydrate. The dentist should have glucose tablets—a rapidly acting,
simple carbohydrate—available in the office at all times. These are inexpensive and have a stable
shelf-life. Each glucose tablet contains 4 g of carbohydrate. If the anticipated procedure is long (eg,
2 hours), then the patient can take the glucose tablets. If the patient initially presents with
hyperglycemia, then the patient can take a small bolus of rapidly acting insulin before the
procedure. This approach is helpful because a long, stressful procedure can lead to endogenous
epinephrine release, mobilization of glycogen from the liver, and additional hyperglycemia.
The most common causes of hypoglycemia include injection of excess insulin, delaying or missing
meals or snacks with the usual dose of insulin, increasing exercise without adjusting the insulin
dose (exercise reduces the requirement for insulin), and consuming alcohol (alcohol inhibits
gluconeogenesis in the liver and thus prevents the release of newly synthesized glucose into the

75
bloodstream). The signs and symptoms include confusion, shakiness (tremors), agitation,
belligerence, sweating (diaphoresis), and tachycardia. The dentist can avoid a hypoglycemic
reaction in a patient by taking an accurate history. The dentist must know the time, dose, and type of
insulin the patient took that day and the time, amount, and type of carbohydrate (simple vs
complex) the patient consumed before the dental visit. In this way, the dentist can match the
patient’s plasma insulin levels with the food intake, thus determining the likelihood of
hypoglycemia.
Hypoglycemic symptoms are more likely to occur if the blood glucose falls below 60
mg/dL. If a glucometer determination shows hypoglycemia, then the administration of glucose
tablets usually rapidly reverses it. If the patient is sedated or unable to take food or drink by mouth,
then 25 to 30 mL of 50% dextrose or 1 mg of glucagon can be administered intravenously,
intramuscularly, or subcutaneously. A glucagon injection causes glycogenolysis in the liver. It will
rapidly reverse hypoglycemia, usually within 15 minutes. In other instances, rubbing a preparation
of glucose (available in most pharmacies) or dissolved sugar under the tongue of the unconscious
patient may reverse the hypoglycemia. The glucose can be rapidly absorbed from the sublingual
site.
In some cases, hyperglycemia can present with symptoms similar to those of hypoglycemia
(eg, confusion and disorientation). If a glucometer is not available to determine blood glucose levels
accurately and the conscious patient has symptoms suggestive of hypoglycemia, then the dentist
must administer glucose tablets (or fruit juice). Treat patients presumptively for hypoglycemia if
they experience tremors, diaphoresis, tachycardia, or disorientation and agitation. If the symptoms
were from hyperglycemia rather than hypoglycemia, then the additional amount of carbohydrate
will generally cause no harm. The rapid development of hyperglycemia with DKA, possibly leading
to diabetic coma, is now, with the advent of the insulin pump, more likely.
More type 1 patients with diabetes are entering pump therapy; therefore, the dentist must be aware
of the signs and symptoms of hyperglycemia and be prepared to manage it. The patient can
administer a small bolus of insulin (by tenths of a unit with a pump) to treat the hyperglycemia. The
patient should also carry a supply of reagent strips to test for ketones in the urine (ketonuria). If the
hyperglycemia and ketonuria persist despite the administration of the insulin bolus, then the dentist
must contact the patient’s physician and refer the patient for immediate medical evaluation. The
best way to determine the true nature of a diabetic emergency quickly is to measure blood glucose
levels with a glucometer. The accuracy of the glucometer readings is generally within an error range
of 5%.

76
 Dental management, Oral complications (Source: Vernillo AT. 21): The oral complications
of uncontrolled diabetes mellitus can include xerostomia, infection, poor healing, increased
incidence and severity of caries, candidiasis, gingivitis, periodontal disease, periapical abscesses,
and burning mouth syndrome. The oral findings in patients with uncontrolled diabetes are most
likely related to the excessive loss of fluids through excessive urination (polyuria), the altered
response to infection, the microvascular changes, and possibly the increased glucose concentrations
in saliva.
A high percentage of diabetic patients present with xerostomia and the complaint of dry mouth.
When the normal environment of the oral cavity is altered because of a decrease in salivary flow or
alterations in salivary composition, a healthy mouth can become susceptible to painful decay and
deterioration. Dry, atrophic, cracking oral mucosa is the eventual complication of xerostomia.
Accompanying mucositis, ulcers, and desquamation—as well as opportunistic bacterial, viral, or
fungal infections and an inflamed, depapillated tongue—are also common problems. Difficulty in
lubricating, masticating, tasting, and swallowing are among the most devastating complications of
xerostomia and may contribute to impaired nutritional intake. An increase in the rate of dental caries
may occur in young diabetic patients; this could be related to the reduced salivary flow. Aside from
topical treatments for xerostomia, improved metabolic control of the diabetes may mitigate the
complications from xerostomia.
Periodontal disease and its impact on diabetic control (Source: Vernillo AT. 21)
In most cases, the dental clinician can manage the well-controlled type 1 or type 2 diabetic
patient in a manner consistent with the management of a healthy nondiabetic person. The dentist
can perform periodontal surgical procedures, although it is important for the patient to maintain a
normal diet during the postsurgical phase. The practitioner should review any previous history of
diabetic complications, determine the most recent test results (eg, glycosylated hemoglobin and
postprandial blood glucose levels), and maintain an ongoing dialogue with the patient’s physician.
Supportive periodontal therapy should be provided at relatively close intervals (2 to 3 months)
because some studies indicate a slight, but persistent, tendency to progressive periodontal
destruction despite effective metabolic control.
The management of the insulin-dependent diabetic requires additional considerations. Before
periodontal surgery, it may be appropriate, in consultation with the patient’s physician, to ask the
patient to administer a small bolus of rapid-acting insulin. This bolus may reduce the hyperglycemia
associated with infection, pain, and stress. If the patient on the multiple-injection dose regimen is
unable to eat after surgery, then the patient must modify the regimen. The patient can eliminate or

77
significantly reduce all rapid-acting insulin for the remainder of the day; this reduces the likelihood
of hypoglycemia in the absence of food during the postsurgical phase. At the same time, the patient
can also reduce his long-acting insulin by a half of the usual recommended dose to prevent
hypoglycemia. There- fore, the patient will have an ongoing basal level of long-acting insulin,
although reduced, that will still ensure glucose homeostasis but prevent further hyperglycemia.
A patient using an insulin pump follows different algorithms for insulin management. If patients are
unable to eat during the postsurgical phase, they may require no adjustment in the basal insulin
program or profile. The programmed insulin release over the 24-hour period may be adequate to
ensure glucose homeostasis. The risk of hypoglycemia is also less than with the multiple insulin
injection regimen because the patient is using the pump. If the patients are unable to eat for more
than 24 hours, they may need to modify the basal profile by increasing the insulin dosage.
Prolonged fasting depletes the finite glycogen stores in the liver. In such a starvation mode, the liver
then uses the pathway of gluconeogenesis to synthesize new glucose from protein; this glucose is
then released into the bloodstream, leading to hyperglycemia. Thus, the patient should increase the
insulin dosage in the basal profile of the pump to maintain glucose homeostasis.
If the periodontal infection is particularly severe, then the patient should also reprogram the basal
profile in the pump to increase the insulin dosage during the postsurgical phase in treatment. By
increasing the insulin dose, the pain and stress from infection and the bacterial endotoxins are less
likely to exert a counterregulatory effect on the liver, which may cause glyco- genolysis and rapid
hyperglycemia with ketoacidosis. These management algorithms are particularly critical because the
patient using an insulin pump is more prone to severe hyperglycemia and DKA. Once there is
adequate resolution of the periodontal infection and a return to a normal diet, the patient can then
reprogram the insulin dosage to the previous basal profile.
A diabetic patient who has the disease under control generally does not require antibiotics after
surgical procedures. However, the administration of antibiotics during the postsurgical phase is
appropriate, particularly if there is significant infection, pain, and stress. A recent study has shown
that the elimination of periodontal infection through the use of systemic antibiotic (doxycycline)
improved the metabolic control of diabetes, as was shown by a reduction in the patient’s
glycosylated hemoglobin value.
Islet cell transplantation (Source: Vernillo AT. 21): Clinical studies have investigated islet
cell transplantation as a treatment for type 1 diabetes mellitus in selected patients with inadequate
glucose control despite insulin therapy. However, the perennial hope that such an approach would
result in long-term freedom from the need for exogenous insulin, with stabilization of the secondary
complications of diabetes, has failed to materialize in practice. Of the 267 allografts transplanted

78
since 1990, only 12.4% have resulted in insulin independence for periods of more than a week, and
only 8.2% have done so for periods of more than a year. However, improved techniques for the
isolation of larger numbers of viable islet cells, along with a modified (corticosteroid-free)
immunosuppressive regimen, have dramatically changed the future of transplantation therapy. 21

7. Dental management of patients with renal diseases

Classification of renal failure (Source: Cervero AJ, Bagan JV, Soriano YJ, et al. 8) : When a
nephron is destroyed it is unable to regenerate, and the kidneys compensate the loss through
hypertrophy of the remaining nephrons, so that normal kidney function can be maintained until
approximately half of all the existing nephrons have been destroyed. Once this point has been
reached, symptoms of renal functional impairment begin to appear:
− Acute renal failure (ARF) is characterized by a sudden and important reduction in
glomerular filtration rate (GFR) lasting for hours or days. The underlying causes are
classified as pre-renal, intrinsically renal or post-renal. In general, renal function is restored
once the underlying cause has been resolved, and it is not common for the dental
professional to treat a patient with ARF. 8

1. Acute renal failure

a) Pre-renal: Gastrointestinal losses, Excessive perspiration, Bleeding, Burns with fluid
sequestration, Renal losses, Cardiovascular failure, Liver failure
b) Intrinsic renal causes: Acute tubular necrosis (vasomotor nephropathy), Severe cortical necrosis,
Severe acute glomerulonephritis, Vasculitis, Malignant hypertension, Accelerated scleroderma,
Allergic interstitial nephritis
Another renal causes: nephrotoxic poisons – sublimate, Ethylene glycol (antifreeze), poisonous
mushrooms; haemorrhagic fever, leptospirosis, acute thrombosis of renal vessels, acute
glomerulonephritis, pyelonephritis etc. 16
c) Post-renal: Bilateral ureteral obstruction or ureteral obstruction in patients with a single kidney,
Bladder obstruction, Bladder rupture, Urethral obstruction
2. Chronic renal failure: Chronic immune glomerulopathy, Hypertensive nephrosclerosis,
Chronic tubulointerstitial diseases, Metabolic diseases (e.g., diabetes mellitus), Congenital and
hereditary renal processes (e.g., renal polycystic disease)

79
 Chronic renal disease (CRD), a progressive and irreversible decline in renal function, is the
renal disease with the most implications in dentistry, so this paper is focused on this pathology.
Kidneys have the following functions: filtering waste metabolic products, preservation of the
electrolytic composition and the volume of the extracellular liquid, regulation of the acid- base
balance and endocrine function (synthesis of prostaglandins, erythropoietin, rennin, vitamin D,-
involved in bone metabolism- and others). As this process develops and the number of functional
units of the kidney or nephrons diminishes, the glomerular filtration rate (GFR) falls, while serum
levels of urea rise, until approaching the stage of renal failure if the patient is not treated. The signs
and symptoms in patients with renal failure are known as “uremic syndrome”. Normal GFR values
are approximately 120- 130ml/ minute/ 1.73 m2, and vary according to age, gender and body size.
This fall is usually measured by creatinine clearance (CC), which gives an acceptable
approximation of the value of GFR. In dental practice, the function of the kidneys can be assessed
indirectly through plasmatic creatinine (Cr). Normal values of serum Cr are 0.5- 1.4 mg/dl; in
patients with renal insufficiency, Cr will be of 1.5 mg/dl or more. Plasmatic Cr can be related to CC
using several formulas, such as Cockcroft-Gault or MDRD (modified diet in renal disease formula).
Presently, the classification of chronic renal disease is guided by the National Kidney Foundation’s
K-DOQI guides (The National Kidney Foundation Kidney Disease Outcomes Quality Initiative) of
2002, which include the following situations:
− Kidney damage during at least 3 months with or without a decrease in glomerular filtration
rate;
− Filtration rate < 60 ml/min/1.73 m2 during more than 2 months with or without kidney
damage.

According to Alamo SM, Esteve CG, Sarrión Pérez MG. in Spain, the exact prevalence of
2
renal pathology remains unknown. According to the EPIRCE study (Epidemiology of Chronic
Renal Insufficiency in Spain), the prevalence of CRD ranges between 1/3 of the population and a
0.7%, depending on the study considered. Diabetes mellitus, arterial hypertension and
glomerulonephritis are the most important etiologic factors of CRD. Treatment of the chronic renal
insufficiency includes dietary changes, correction of systemic complications, and dyalisis or a renal
graft. The most common cause of death in patients with end stage renal failure is cardiac arrest,
followed by infection and malignancy.
These patients can suffer a spectrum of oral manifestations and dental treatment must be
adapted to the systemic disease.

80
 Oral manifestations: Up to 90% of patients with renal insufficiency show oral signs and
symptoms in soft and hard tissues, some of them being a cause of the disease itself and others
deriving from the treatment of the pathology. The diminished function of the kidneys results in an
increase in the levels of urea in the blood and also in the saliva, where it will turn into ammonia. For
this reason, uremic individuals have a characteristic halitosis (uremic fetor), which also occurs in
about one-third of hemodyalized patients. This halitosis is related to another manifestation: the
perception of an unpleasant, metallic taste. Apart from urea, other factors possibly implied are the
increase in the concentration of phosphates and proteins and changes in the pH of saliva. Also, these
patients can refer sensitive disturbances, like altered taste sensations – especially, sweet and acid
flavors. These can be due to the high levels of urea, the presence of dimethyl- and trimethyl-
amines, or low zinc levels (due to the malabsorption derived from gastrointestinal disorders). There
can also be a burning sensation in the lips and tongue, of a neuropathic origin or even a sensation of
an enlarged tongue. A decrease in salivary secretion occurs as a consequence of liquid intake
restrictions, secondary effects of medication (mainly antihypertensives), possible glandular
involvement (atrophia of minor salivary glands’ parenchyma), and mouth breathing. This
manifestation is associated with the loss of taste perception. Sometimes these individuals are
afflicted by anemia due mainly to the decrease in the synthesis of erythropoietin, which can be
clinically observed as a skin and mucosa paleness. Uremic stomatitis is an oral complication of
unknown etiology and it is relatively uncommon usually seen in patients with an end stage or
untreated renal disease. Clinically, it is characterized by the presence of erythematous lesions which
are localized or generalized. These lesions are covered by a pseudomembranous exudate that can be
removed, leaving an intact or ulcerated mucosa. As there are no histological patognomonic signs of
this manifestation, the definitive diagnosis will be made combining clinical findings and excluding
other diseases with the histopathology. It does not require a specific treatment and an involution will
usually occur after uremia is restored; but in order to assist lesion healing, 10% hydrogen peroxide
gargles (1:1 in water), 4 times a day, can be recommended. With regard to dental anomalies in these
patients, delayed eruption in children with CRD has been reported. Another sign frequently found in
children is the presence of enamel hypoplasias, due to alterations in calcium and phosphorus
metabolism. In adults with CRD, narrowing or calcification of the pulp chamber can occur. This is
reportedly more severe in graft recipients than in individuals receiving hemodialysis. There is no
consensus between authors whether dental caries are more prevalent in patients with CRD;
however, there is no firm evidence to suggest that there is. Sometimes an antibacterial effect has
been attributed to the increase of the pH (due to urea hydrolization by saliva), which suggests a
protective function against caries. However, non- carious tooth tissue loss is more prevalent in

81
individuals with CRD than in the general population. This may be due to nausea, esophageal
regurgitation, or induced vomiting in bulimia nerviosa (in patients who dislike the restrictive diet,
which is suggested as a part of the treatment). The majority of studies agree that there is a greater
incidence of periodontal disease, bone loss, recessions and deep periodontal pockets. Other oral
manifestations of the CRD are related to renal osteodystrophy. This is a late sign of renal disease
due to alterations in calcium and phosphorum metabolism, abnormal metabolism of vitamin D and
the compensatory hyperactivity of parathyroid glands (secondary hyperparathyroidism). It is
characterized by the following signs: bone demineralization, decreased trabeculation, decreased
thickness of cortical bone, ground- glass appearance of bone, metastatic soft- tissue calcifications,
radiolucent fibrocystic lesions, radiolucent giant cell lesions, lytic areas of bone, jaw fracture
(spontaneous or after dental procedures), abnormal bone healing after extraction, and, sometimes,
dental mobility as a consequence of loss of substance in the bone. Bleeding tendency in these
patients may be due to factors depending on the disease itself, like alterations in platelet aggregation
and renal anemia (secondary to deficient erythropoiesis); and to dyalisis, which diminishes platelet
recount due to mechanical damage and heparin anticoagulation during this process. For that reason,
it can be concluded that hemodialysis predisposes to ecchymosis, petechiae and hemorrhage in the
oral mucosa. Oral hygiene of patients receiving hemodyalisis is usually poor, so deposits of calculus
and plaque may be increased. Treatment received by patients with renal disease also produces oral
clinical manifestations. In particular, lichenoid disease may arise, associated with antihypertensive
medication (diuretics, beta- blockers). Kidney- transplanted patients are given a lifelong
immunosuppressive therapy, and therefore more susceptible to infections and to the development of
malignant neoplasms. Furthermore, they are frequently afflicted by a secondary effect of the
medication: gingival overgrowth. Where fungal infections are concerned, there are mainly lesions
related to Candida albicans. Angular cheilitis has been reported in more than 4% of patients
receiving hemodialysis or who have undergone transplantation. Other forms of candidosis have
been reported in allograft recipients: pseudomembranous (1.9%), erythematous (3.8%), chronic
atrophic – also called prosthetic stomatitis (3.8%). It should be highlighted that these figures may
underestimate the increased susceptibility of immunosuppressed allograft recipients to fungal
infection, since systemic anti- fungal agents are commonly prescribed prophylactically. The herpes
group of viruses, in particular cytomegalovirus (CMV) and herpes virus simplex (HSV), are
frequently associated with immunosuppresed organ transplant recipients. Mucosal ulceration is
often associated with CMV, having a predilection for the lateral borders of the tongue. Due to this
immunosuppresion, a reactivation of HSV, characterized by the onset of recurrent, severe and long-
standing infections. Clustered vesicles on an erythematous base may arise, or, more atypically, a

82
lone lesion. They can appear either in labial mucosa or intraorally, having a predilection, in the
latter, for keratinized epithelium. Vesicles on mucosal surfaces rapidly erode and leave an ulcerated
area. In the case of recurrent infections of HSV in these patients, doses of 400 mg of acyclovir can
be administered orally, 3 times a day during 10 days or more (usually, more than 2 weeks). Long-
standing immunosuppresion also predisposes to infection by herpes human virus- 8 (HHV-8),
related to Kaposi’s sarcoma. Hairy leukoplakia occurs in immunosuppresed patients (11% of renal
transplant recipients), and it is associated with the Epstein- Barr virus. It is important to make a
differential diagnosis in cases of chronic pseudomembranous candidosis –white lesions that can be
removed. Regarding malignant tumors, lymphomas, Kaposi’s sarcoma (KS) and oral squamous cell
carcinoma of the lip, are the most frequent in the stomatologic area. Approximately 86% of the
lymphomas are Non- Hodgking lymphomas (NHL) of B cells. Gingival overgrowth (GO)
secondary to the immunosuppressive therapy is the most studied oral manifestation. An estimated
30% of dentate patients medicated with cyclosporine alone experience clinically significant gingival
overgrowth (GO). When patients are medicated with a combination of cyclosporine and nifedipine,
the prevalence of gingival overgrowth increases to 50%. This effect occurs within 3 months of
treatment. Age is an important determining factor for this unwanted effect, since children are more
susceptible than adults. The pathogenesis of this disorder is multifactorial, but it is thought that the
key factors are drug variables, plaqueinduced inflammation, the susceptibility of gingival
fibroblasts and also genetic factors, as not all patients treated with Cs develop gingival overgrowth.
There are multiple pharmacologic agents that can produce the unwanted effect of GO, such as
anticonvulsivants or antiepileptics (phenytoin, sodium valproate, phenobarbital, vigabatrin),
immunosuppressants (cyclosporine), calcium channel blockers (nifedipine, verapamil, diltiazem,
oxodipine, amlodipone) and others. Although some slight hystopathological differences have been
found, gingival overgrowth produced by different drugs is clinically indistinguishable. The
combination of drugs that most frequently produces this side effect is Cs and nifedipine, used in
renal transplant recipients. Gingival overgrowth is usually confined to attached gingiva but may
extend coronally and interfere with occlusion, mastication and speech. This overgrowth, which
normally begins at the interdental papillae, is more common in the anterior segments of the mouth
and on labial surfaces of teeth. It does not seem to have a predilection for the maxilla or the
mandible. It has also been noted that overgrowth associated with the canine teeth is significantly
greater. GO does not seem to arise in edentulous patients or edentulous spaces. The role of plaque in
Cs induced GO has been discussed in literature, but it has not been possible to determine if GO is a
cause or a consequence. Plaque accumulation associated with the difficulty in maintaining proper
oral hygiene, and also other local irritant factors (prosthesis, brackets, etc.), make gingival

83
inflammation worse, and increase the severity of GO. Improvement of oral hygiene achieves a
reduction in GO related to cyclosporine. Cs has many side effects, including GO, which this has
motivated the search of therapeutic alternatives. Recently, tacrolimus (FK506, Prograf®),
rapamycin (RS 61443) and mophetil mycophenolate (CellCept®) have been used. However, they
are more expensive and their side effects are still not well- known. For these reasons, in the
majority of cases, Cs remains the first option.
Dental considerations and management of the patient with chronic renal disease
(Source: Alamo SM, Esteve CG, Sarrión Pérez MG. 2).
The most important features in these patients are bleeding tendency, hypertension, anemia,
drug intolerance, increased susceptibility to infections and the presence of several manifestations
associated with either the disease or its treatment. Many antibiotics are actively removed by the
kidney, so and adjustment of the dosage by amount or by frequency is required. Penicillin (and its
derivates, such as amoxicillin), clyndamicin and cephalosporins are the preferred antibiotics for
these patients. In the case of non- narcotic analgesics, paracetamol is the best choice. It is preferable
to avoid the remaining non- steroidal anti- inflammatory drugs (ibuprofen, naproxen and sodium
diclophenate), as they produce hypertension. Benzodiazepines can be prescribed without dose
adjustment. Narcotic analgesics (codeine, morphine, phentanile) do not need a dose adjustment
either. Table 18 shows dose adjustment of some of the most used drugs in dentistry, depending on
creatinine clearance. With regard to GO, when it is severe, a surgical treatment should be performed
(gingivectomy). The clinical decision of performing the surgery is based generally in the presence
of functional discomfort and esthetic alteration. Nevertheless, this treatment is not definitive:
estimated recidives account for a 50%. A change in the immunosuppressive therapy is an alternative
to surgical treatment, but it is not always possible. There are some good alternatives to Cs, such as
tacrolimus. Adverse effects of tacrolimus are similar to those of Cs but milder, and furthermore it
does not produce gingival overgrowth.

DOSE ADJUSTMENT ACCORDING TO CREATININ CLEARANCE

DRUGS Normal dose Dose with CC 10- 50 Dose with CC <10 ml/
ml/ min min
ANTIBIOTIC
Amoxicillin 500/ 1000 mg/ 8 h 500/ 1000 mg/ 8-12 h 500/ 1000 mg/ 12- 24 h
Amoxicillin/clavulanat 500/ 875 mg/ 8 h No need for dose 500/ 875 mg/ 12- 24 h
e adjustment
Penicillin G 0’3- 1’2 million IU/ 6- 50- 100% of the dose 25- 50% of the dose

84
 12 h every 8- 12 h every 12 h
Clindamycin 300 mg/ 8 h No need for dose No need for dose
adjustment adjustment
Doxiciclin 100 mg/ 24 h No need for dose No need for dose
adjustment adjustment
Erythromycin 250- 500 mg/ 6 h No need for dose No need for dose
adjustment adjustment
Metronidazole 250- 500 mg/ 6 h Every 8-12 h Every 12- 14 h
Azithromycin 500 mg/ 24 h, 3 days No need for dose No need for dose
adjustment adjustment
ANTIFUNGALS
Anfotericin 0’3- 1 mg/kg/ 24 h No need for dose 0’3- 1 mg/ kg/ 24- 48 h
adjustment
Fluconazol 100- 200 mg/ 24 h 50- 200 every 24 h 50- 100 every 24 h
ANALGESICS
Paracetamol 500- 1000 mg/ 4- 6 h No need for dose No need for dose
adjustment adjustment
Aspirin Contraindicated
(produces water
retention, deterioration
of renal function and
risk of gastric
hemorrhage)
Ibuprofen 200- 600 mg/ 4- 6 h No need for dose No need for dose
adjustment adjustment
Dihidrocodeine 10- 30 mg/ 4- 6 h Decrease dose 25% Decrease dose 25%

CC: Creatinin clearance.

Table 18. Dose adjustment according to creatinin clearance of the drugs more frequently
prescribed in dentistry, Source: Alamo SM, Esteve CG, Sarrión Pérez MG. 2
a. Patient with renal disease in conservative medical treatment (Source: Alamo SM, Esteve
CG, Sarrión Pérez MG. 2). For the dental treatment of these patients, good communication with
their nephrologist is highly recommended, in order to be aware of the stage of the pathology
suffered and the treatment prescribed. Before any invasive dental procedure, possible hematologic
problem in the patient should be studied. It is essential to remove any infective foci as soon as
possible. Due to the frequent hypertension, blood pressure should be monitorized monitored during
the procedures. When prescribing drugs, those that are nephrotoxic must be avoided (tetracyclines,
aminoglycosides), some of them need a dose adjustment. Apart from these considerations, no more

85
exceptional measures must be performed.
b. Patient with renal disease in peritoneal dyalisis. Dental management (Source: Alamo SM,
Esteve CG, Sarrión Pérez MG. 2). In cases of peritoneal dyalisis, a catheter placed in the abdominal
wall and inserted in the peritoneum achieves access to the body, in order to remove nitrogen and
other metabolic toxic products; through this, a hypertonic glucosated solution is introduced.
Peritoneal membrane of the patient filters blood waste products by means of an osmotic
mechanism, so they would be transferred to the electrolytic solution and then evacuated to the
exterior. This form of dyalisis can be performed at home, but must be done every day.
c. Patient with renal disease in hemodialysis, dental management (Source: Alamo SM,
Esteve CG, Sarrión Pérez MG. 2): In hemodialysis, the filtering process is carried out by a machine
(dialyzer), outside the patient’s body. Most of these patients receive this treatment 3 times a week.
In order to take the blood out of the body and to return it, it is necessary to have a vascular access.
Permanent access is obtained by surgically connecting an artery to a vein, using a blood vessel
(arteriovenous fistula) or a synthetic bridge (arteriovenous graft). A special solution (dyalisate)
corrects the chemical disturbances and impurities of the blood, which is then introduced into the
body. During the process of hemodialysis, the patient’s blood is anticoagulated with heparin to
facilitate blood transit. For this reason, dental treatments with a risk of bleeding must not be
performed the day of hemodialysis. If an emergency dental treatment must be performed, protamine
sulphate (heparin antagonist) can be administered to block the anticoagulant effect. However,
bleeding tendency would be still present due to platelet dysfunction and anemia, so usual
hemostatic measures must be carried out. There is a risk of infection because of the vascular access,
and of transmission of HBV, HCV and HIV, so this must be confirmed in patients receiving
hemodialysis. Dental considerations for the patients in hemodialysis are synthesized in Table 19.

SITUATION
Patient with medical problems treated by other
professionals
High prevalence of arterial hypertension
Platelet dysfunction and anemia (bleeding
tendency)
Heparin anticoagulation
ATTITUDE
- Consultation with the nephrologist
- Accurate medical history (medication
prescribed)
Monitorization of blood pressure pre and
postoperatively
- Request hemostatic study before planning the
surgery (time of bleeding, platelet recount,
hematocrite, hemoglobin)
- Local hemostatic measures
Perform dental treatment the day not receiving

86

Vascular access for hemodialysis
Disturbances in the metabolism and removal of
drugs
Renal osteodystrophy due to secondary
hyperparathyroidism (late sign of chronic renal
insufficiency)
dialysis, to be sure that there is no heparin in the
blood (mean life of 4 hours)
Avoid compression on the arm with the vascular
access and never use it to measure blood pressure
nor administering drugs intravenously
Some drugs must not be prescribed and some
need dose adjustment. Request the CC to estimate
the GFR
- Bone more susceptible to fractures
- Careful dental extraction technique to avoid
fractures

CC: Creatinin clearance. GFR: Glomerular filtrarion rate.

Table 19. Dental management of the patient receiving hemodialysis, Source: Alamo SM,
Esteve CG, Sarrión Pérez MG. 2

d. Renal transplant patient, dental management (Source: Alamo SM, Esteve CG, Sarrión
Pérez MG. 2): These patients are immunosuppressed by medication. Maintenance of a proper oral
health is especially important as oral infections in transplant patients can contribute to its morbidity
or even rejection. They are usually receiving a treatment of corticosteroids, calcineurin inhibitors
(Cs, tacrolimus) and inhibitors of lymphocyte proliferation (azathioprine, mycophenolate mophetil).
Long- standing treatment with high doses of corticosteroids produces an adrenal function
suppression, which predisposes the patient to suffer an acute complication, adrenal crisis, when
exposed to stressful situations (disease, infection, surgery). Furthermore, this chronic excess of
corticosteroids can cause Cushing’s syndrome. To minimize the risk of suffering an adrenal crisis in
patients taking high doses of corticosteroids who are undergoing a surgical procedure, they should
take a double dose of corticosteroids the day of the surgery. This supplement will not be necessary
if the patient is being treated with low doses (less than 7.5 mg of prednisolone) or if the patient is
undergoing a conservative treatment. However, the risk of developing an adrenal crisis after oral
surgery procedures under local anesthesia is very low and the majority of dental treatments can be
carried out without prescribing a supplement of corticosteroids. Considerations that must be taken
into account in renal transplant individuals are described in Table 20. 2

87
 SITUATION
Patient with medical problems treated by other
professionals
High prevalence of arterial hypertension
Platelet dysfunction and anemia (bleeding
tendency)
Corticosteroid therapy
Immunossuppression
Disturbances in the metabolism and removal of
drugs
Gingival overgrowth (cyclosporin, nifedipin)
ATTITUDE
- Consultation with the nephrologist
- Accurate medical history (medication
prescribed)
Monitorization of blood pressure pre and
postoperatively
- Request hemostatic study before planning the
surgery (time of bleeding, platelet recount,
hematocrite, hemoglobin)
- Local hemostatic measures
Risk of adrenal crisis if they are in a long-
standing corticosteroid therapy: morning
appointments and consider the need of
supplemental corticosteroids
Prescribe antibiotic prophylaxis, if recommended
by the nephrologist, prior to certain treatments:
tooth extractions, periodontal treatments,
subgingival placement of fibers or strips with
antibiotic, placement of orthodontic bands and
intraligamentous injections of local anesthesic
Some drugs must not be prescribed and some
need dose adjustment. Request the CC to estimate
the GFR
Perform exhaustive examinations of the gums
and promote good oral hygiene. Consider surgical
treatment

CC: Creatinine clearance. GFR: Glomerular filtration rate.

Table 20. Dental management of renal transplant patient, Source: Alamo SM, Esteve CG,
Sarrión Pérez MG. 2

8. Dental considerations in patients with liver disease

Introduction (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. 11): Liver
diseases are very common and can be classified as acute (characterized by rapid resolution and
complete restitution of organ structure and function once the underlying cause has been eliminated)
or chronic (characterized by persistent damage, with progressively impaired organ function
secondary to the increase in liver cell damage). Based on the extent and origin of the damage,
chronic liver disease ranges from steatosis or fatty liver to hepatocellular carcinoma, and includes
hepatitis, fibrosis and cirrhosis. Liver diseases can also be classified as infectious (hepatitis A, B, C,
D and E viruses, infectious mononucleosis, or secondary syphilis and tuberculosis) or non-

88
infectious (substance abuse such as alcohol and drugs, e.g., paracetamol, halothane, ketoconazole,
methyldopa and methotrexate). The liver has a broad range of functions in maintaining homeostasis
and health: it synthesizes most essential serum proteins (albumin, transporter proteins, blood
coagulation factors V, VII, IX and X, prothrombin and fibrinogen, as well as many hormone and
growth factors), produces bile and its transporters (bile acids, cholesterol, lecithin, phospholipids),
intervenes in the regulation of nutrients (glucose, glycogen, lipids, cholesterol, amino acids), and
metabolizes and conjugates lipophilic compounds (bilirubin, cations, drugs) to facilitate their
excretion in bile or urine. Liver dysfunction alters the metabolism of carbohydrates, lipids, proteins,
drugs, bilirubin and hormones. Accordingly, liver disease is characterized by a series of aspects that
must be taken into account in the context of medical and dental care. Since many drug substances
are metabolized in the liver, it is essential for the clinician to compile a complete medical history,
evaluating all body systems and the medication used by the patient. The patient drug metabolizing
capacity can be evaluated based on the analysis of enzymes such as alanine aminotransferase (ALT)
or aspartate aminotransferase (AST), and other liver function tests. In situations of advanced liver
disease, the vitamin K levels can be significantly lowered, thus giving rise to a reduction in the
production of blood coagulation factors. In addition, portal hypertension can scavenge platelets
formed in the spleen, thus giving rise to thrombocytopenia. This in turn can lead to an excessive
bleeding tendency, which is one of the main adverse effects seen during the treatment of patients
with impaired liver function. Dentists are particularly at risk of hepatitis B and C contagion, due to
the transmission routes of these viruses, since these professionals are exposed to the blood and oral
secretions of potentially infected individuals – particularly in the case of accidents with sharp or
cutting instruments.

a. Viral hepatitis
According to Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. hepatitis of viral
origin comprises a heterogeneous group of diseases caused by at least 6 different types of viruses:
A, B, C, D, E and G. 11

11
Hepatitis A (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. ):
Hepatitis A is caused by the hepatitis A virus (HAV), an RNA picornavirus endemic in many
developing countries. Its estimated prevalence is 1.1%. This virus is transmitted via the enteral
(oral-fecal) route, as a result of the ingestion of contaminated water or food (mollusks), though
intrafamilial contagion has also been described, as well as contagion in closed institutions and

89
secondary to sexual intercourse. The disease is typically mild and self-limiting, and is characterized
by the sudden onset of nonspecific symptoms. There is no carrier state. In children or young
individuals the disease tends to be asymptomatic, while adults typically present fever, fatigue,
abdominal discomfort, diarrhea, nausea and/or jaundice. The patient is able to transmit the infection
during the incubation period (2-6 weeks) and until the appearance of symptoms. The diagnosis is
based on the signs and symptoms and on serological testing for anti-HAV IgM and IgG antibodies.
Host response in the form of anti-HAV antibodies affords lifelong immunity, protecting the patient
against future HAV infection. The risk of nosocomial contagion among healthcare personnel is quite
low. Vaccines are available that offer immunity against HAV (Havrix®, Vaqta®) for people at risk
(i.e., subjects traveling to endemic areas, drug abusers, patients with chronic liver disease and
subjects with occupational risk factors).
11
Hepatitis B (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. ): The
hepatitis B virus (HBV) is an encapsulated DNA virus that replicates within the hepatocyte.
Hepatitis B is a worldwide health problem, with an estimated 400 million carriers of the virus. It has
been calculated that 1.53% of all patients reporting to the dental clinic are HBV carriers. The
transmission routes comprise sexual contact, intravenous drug use and blood transfusions. An
important consideration among dental professionals is the risk of percutaneous transmission through
punctures or cuts with instruments infected from HBV-positive patients, or absorption through the
mucosal surfaces (eyes, oral cavity). Transmission through saliva can occur as a result of absorption
from mucosal surfaces. Some studies have reported the presence of HBsAg in saliva and crevicular
fluid of HBV-positive patients. Dental professionals, particularly those dedicated to oral surgery,
have a three- to four-fold greater risk of HBV infection than the general population, though
vaccines and barrier methods have contributed to lessen the risk. Following inoculation, the
seroconversion risk is 30%. The incubation period lasts 2-6 months. Over 50% of all infections are
subclinical and are not associated with jaundice. In this context, since the disease may prove
asymptomatic, many people are unaware that they have suffered the infection in the past.
Approximately 90% of all HBV-infected adults show complete healing, but 5-10% develop chronic
hepatitis with complications in the form of cirrhosis and hepatocellular carcinoma, resulting in
5000-6000 deaths a year due to liver failure. The disease is diagnosed by quantifying the levels of
HBV DNA, HBsAg and the antigen / antibody ratio. Vaccines have been developed that induce an
effective immune response against the virus in most patients. If a non-immunized individual
becomes exposed to HBV, immunoglobulin can be administered to afford protection after exposure.
The current management protocols include HBV immunization as part of the pediatric vaccination
program.

90
 11
Hepatitis C (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. ):
Hepatitis C virus (HCV) infection is the main cause of chronic liver disease and of liver-related
morbidity and mortality worldwide. It has been estimated that 8000 to 10,000 deaths a year are
attributable to HCV, and the latter represents the main indication for liver transplantation in Europe
and the United States. The estimated global prevalence of the disease is 2.2%, representing
approximately 130 million infected individuals in the world. Great geographical variability is
observed, possibly as a result of immunogenetic factors. The lowest prevalences are found in the
United Kingdom and Scandinavia, and the highest in Egypt. HCV is an RNA virus mainly
transmitted via the parenteral route from infected blood. The sources of contagion include blood
transfusion (although the risk has been minimized since donor blood tests and controls are made,
percutaneous exposure through contaminated instruments, and occupational exposure to blood. The
individuals at greatest risk are hemophiliacs, patients on dialysis and parenteral drug abusers. Other
transmission routes are sexual contact and perinatal and idiopathic contagion. The prevalence of the
infection among dental professionals is similar to that found in the general population, though
epidemiological studies suggest that dentists constitute a risk group for HCV infection. Following
inoculation, the estimated seroconversion risk is 1.8%. The incubation period is long (up to three
months), and 85% of all patients with HCV infection develop chronic hepatitis. In those cases
where symptoms are observed, these tend to be mild, and most subjects remain relatively
asymptomatic during the first two decades after infection with the virus. The morbidity associated
to HCV infection is due not only to the consequences of chronic liver disease but also to the
extrahepatic manifestations. The best documented condition associated to hepatitis C is
cryoglubulinemia, a multisystemic disorder often characterized by purpura, weakness and joint
pain, and which may precede the development of B-cell non-Hodgkin lymphoma or membrane
proliferative glomerulonephritis. Other related disorders are porphyria cutanea tarda, lichen planus,
sialadenitis, thyroid gland dysfunction, diabetes mellitus and peripheral neuropathy. Over 74% of
all HCV-infected patients ultimately develop extrahepatic manifestations in the course of the
infection. Different enzyme-linked immunosorbent assay (ELISA) and recombinant immunoblot
assay (RIBA) techniques have been developed for the diagnosis of HCV infection, though the
diagnostic gold standard remains detection of the viral genome using real time polymerase chain
reaction (RT-PCR) technology. No effective vaccine against HCV has yet been developed, and
spontaneous resolution is unusual. The existing therapy comprises combination treatment with
interferon and ribavirin, which offers a sustained response rate of 30-40%.

91
 Chronic hepatitis (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. 11)
Chronic hepatitis is a diffuse inflammatory disorder of the liver with a duration of over 6
months in which the underlying cause can be infectious (mainly hepatitis C virus and, to a lesser
extent, hepatitis B and D viruses), pharmacological or immunological. The disease can develop in
the absence of symptoms or with nonspecific manifestations such as fatigue, nausea or abdominal
pain. The course is normally slow and progressive, and symptoms typically do not manifest until
years after the initial causal event (e.g., infection). Some patients develop the disorder without
significant liver damage, while others rapidly progress towards cirrhosis and possible
hepatocarcinoma. Chronic hepatitis due to HCV infection is the principal cause of cirrhosis and
hepatocellular carcinoma.
b. Alcoholic liver disease (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez
MG. 11)
Alcoholic liver disease is one of the 10 most common causes of death in the industrialized
world, and is responsible for 3% of all fatalities. The epidemiological data indicate a threshold of 80
g of alcohol in males and 20 g in females, consumed on a daily basis during 10-12 years, in order to
cause the corresponding liver damage. Ten grams of pure ethanol are equivalent to a glass of wine
or a beer, while a glass of whiskey doubles that amount. Factors such as chronic hepatitis C
infection, obesity and genetic factors can accelerate the development of alcoholic liver disease even
with smaller doses of alcohol. Alcoholism is characterized by physical dependency that includes
great tolerance of large amounts of alcohol in blood, a strong urge to drink, difficulty controlling
consumption, progressive abandonment of usual daily life activities, and persistence of the habit
despite its consequences. Alcoholism in turn leads to malnutrition, anemias, diminished immune
function and important drug interactions. The clinical spectrum of alcoholic liver disease ranges
from simple liver steatosis (fatty liver) with alcoholic (toxic) hepatitis to more severe steatohepatitis
or cirrhosis. Simple steatosis is the most common presentation, is found in 90% of all heavy
drinkers, and proves reversible upon abandoning the habit. Alcoholic hepatitis is observed in over
35% of all heavy drinkers and tends to be a precursor of cirrhosis. The condition ranges from
asymptomatic forms to liver failure and life-threatening situations, and is usually accompanied by
febricula, jaundice, leukocytosis and liver enzyme elevations.
c. Non-alcoholic fatty liver (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-
Pérez MG. 11)
Non-alcoholic fatty liver is defined as the accumulation of fat (mainly triglycerides) in the
liver, representing over 5% of the weight of the organ, in the absence of alcohol consumption in

92
excess of 10 g a day. The observed liver damage ranges greatly from simple steatosis (accumulation
of fat in the liver) to steatohepatitis (fat accumulation with added inflammation), advanced fibrosis
and cirrhosis. This disorder is mainly associated to obesity, diabetes, hyperlipidemia and insulin
resistance. There is a strong correlation between insulin resistance and excessive triglyceride
accumulation within the liver cells. However, 16.4% of all patients with non-alcoholic fatty liver
present none of these predisposing factors. The condition is potentially reversible after eliminating
or minimizing the aforementioned causal factors. No clear treatments have been established to date
for non-alcoholic fatty liver, though interventions such as bariatric surgery (in the case of obese
individuals) and oral antidiabetic drugs (glitazones) in patients with type 2 diabetes have shown
encouraging results.
d. Cirrhosis (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. 11)
Liver cirrhosis is very common in our setting, with well defined morphopathological
characteristics that lead to destruction of the liver parenchyma. The disease is accompanied by a
series of extrahepatic manifestations in other body organs and system. Liver cirrhosis is irreversible,
and is characterized by the formation of fibrous scarring in the liver, with the formation of
regeneration nodules that increase resistance to blood flow through the organ. The resulting
deficient liver perfusion damages vital structures in the organ and adversely affects its physiological
functions. The main causes of liver cirrhosis are hepatitis B and C infection and alcohol abuse.
Other potential causes are non-alcoholic steatohepatitis, genetic alterations and autoimmune
disorders. The main complications of cirrhosis are portal hypertension, hepatocellular carcinoma
and organ function loss. Cirrhosis in itself constitutes a risk factor for the development of
hepatocellular carcinoma. The treatment options comprise suppression of the causal stimulus,
antiviral therapy and liver transplantation in the end stages of cirrhotic disease.
e. Hepatocellular carcinoma (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-
Pérez MG. 11)
Hepatocellular carcinoma is the fifth most frequent cancer worldwide. As such, it constitutes
an important public health problem, and is one of the most common and life-threatening
malignancies in the world – with a survival rate after two years of only about 2%. It has been
estimated that HBV and HCV are responsible for over 80% of all hepatocarcinomas. The other
causes are alcoholic and non-alcoholic steatohepatitis. Most patients with hepatocellular carcinoma
have a history of cirrhosis, which in itself constitutes a preneoplastic condition. Liver cirrhosis has a
prolonged natural course, and produces symptoms only in the advanced stages of the disease, when
no healing treatment options are available. The main treatment for hepatocellular carcinoma is

93
surgery (in those cases where the tumor proves resectable), though unfortunately many cases are
non-operable due to the proximity of vital structures, the presence of metastases, or other
comorbidities.
Oral clinical manifestations (According to Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-
Pérez MG. 11)
The oral cavity can reflect liver dysfunction in the form of mucosal membrane jaundice,
bleeding disorders, petechiae, increased vulnerability to bruising, gingivitis, gingival bleeding (even
in response to minimum trauma), foetor hepaticus (a characteristic odor of advanced liver disease),
cheilitis, smooth and atrophic tongue, xerostomia, bruxism and crusted perioral rash. In these
patients, chronic periodontal disease is a common finding. Patients with alcoholic hepatitis can
present glossitis, angle cheilitis and gingivitis, particularly in combination with nutritional
deficiencies. Some patients who consume large amounts of alcohol for prolonged periods of time
can develop sialadenosis.
Patients with advanced cirrhosis tend to present deficient oral hygiene, particularly in those
cases where the liver impairment is associated to alcohol abuse. Extrahepatic manifestations have
been reported in 74% of all HCV-infected individuals, and some of these conditions predominantly
or exclusively affect the oral region. The main disorders associated with HCV infection are
xerostomia, Sjögren’s syndrome (SS), sialadenitis and particularly lichen planus (LP). Xerostomia
increases patient vulnerability to caries and oral soft tissue disorders which, in combination with
deficient hygiene, in turn facilitate the development of candidiasis. It has not yet been demonstrated
whether HCV infection causes disease similar to primary Sjögren’s syndrome or whether it is
directly responsible for development of Sjögren’s syndrome in certain types of patients. However, it
is notorious that some subjects can present a triple association of HCV infection, Sjögren’s
syndrome and sialadenitis or salivary gland lymphoma. Although bacteria are the main cause of
sialadenitis, viruses such as HCV have been implicated as causes of sialadenitis associated to
xerostomia. Lichen planus may be significantly associated to HCV infection.
Dental management (Source: Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG.
11
): Liver disease has important implications for patients receiving dental treatment. The most
frequent problems associated with liver disease in clinical practice refer to the risk of viral
contagion on the part of the dental professionals and rest of patients (cross-infection), the risk of
bleeding in patients with serious liver disease, and alterations in the metabolism of certain drug
substances which increases the risk of toxicity. HCV has been detected on different surfaces within
the dental clinic after treating patients with hepatitis C, and the virus moreover is able to remain

94
stable at room temperature for over 5 days. Strict sterilization measures are therefore required, since
deficient sterilization can expose both the dentist and other patients to hepatitis infection. The
universal protective measures are applicable in order to prevent cross-infection, i.e., the use of
barrier methods, with correct sterilization and disinfection measures. It has been demonstrated that
conventional sterilization techniques eliminate specific proteins and nucleic acids (HBV DNA and
HCV RNA) from dental instruments previously infected with HBV and HCV. Although there are no
data confirming their efficacy in lessening the risk of contagion, the measures recommended in the
case of accidental perforation of the skin with instruments or needles comprise careful washing of
the wound (without rubbing, as this may inoculate the virus into deeper tissues) for several minutes
with soap and water, or using a disinfectant of established efficacy against the virus (iodine
solutions or chlorine formulations). In turn, pressure should be applied beneath the level of the
wound in order to induce bleeding and thus help evacuate any possible infectious material. If
exposure through some mucosal membrane has occurred, abundant irrigation with tap water, sterile
saline solution or sterile water is advised, for several minutes. The rationale behind these measures
is to reduce the number of viral units to below the threshold count needed to cause infection (i.e.,
the infectious dose). In this sense, dilution with water may lower the viral count to below this
threshold. Whenever possible, the hepatitis antigen status of the patient should be determined. In the
event of parenteral exposure to hepatitis viruspositive antigens, the dentist should receive treatment
with anti-hepatitis B immunoglobulin. Table 21 offers a schematic description of the steps to be
followed. The compilation of a detailed clinical history is essential before dental treatment in order
to identify patients posing possible risks, together with a thorough oral exploration.
Interconsultation with the patient physician or specialist is advisable in order to establish a safe and
adequate treatment plan adapted to the medical condition of the patient, considering the degree of
liver functional impairment involved. Exploration of the oral cavity should assess any signs alerting
to the existence of systemic disease. The patient should receive an explanation of the risks
associated with treatment, and informed consent is to be obtained. In patients with acute-phase viral
hepatitis, only emergency treatment should be considered. In subjects with chronic hepatitis it is
important to determine the possible existence of associated disorders (autoimmune processes,
diabetes, etc.) in order to prevent their direct complications and problems derived from specific
medication use (corticosteroids and/or immune suppressors). Evaluation is also required of the
possible medical conditions associated to HCV contagion, fundamentally blood transmitted
infections (HIV, HBV). It also must be taken into account that liver disease is often associated with
a decrease in plasma coagulation factor concentrations. In a patient with liver disease, the surgical
risk is related to the severity of the disease, the type of surgery planned, and the presence of

95
comorbidities. Surgery is contraindicated in patients with certain conditions such as acute hepatitis,
acute liver failure or alcoholic hepatitis. If invasive measures are required, prior coagulation and
hemostasis tests are required: complete blood count, bleeding time, prothrombin time / international
normalized ratio (INR), thrombin time, thromboplastin time and liver biochemistry (GOT, GPT and
GGT). Table 22 reports the normal coagulation test values. In the event altered test values are
detected, the hematologist or liver specialist should be consulted, with the postponement of elective
treatment. Any emergency treatments should be provided in the hospital setting. In the event of
surgery, trauma should be minimized in order to optimize hemostasis, with a careful surgical
technique, applying pressure to control bleeding and using hemostatic agents. Based on the
laboratory test findings and the treatment to be carried out, local hemostatic agents may be
advisable (oxidized and regenerated cellulose), as well as antifibrinolytic agents (tranexamic acid),
fresh plasma, platelets and vitamin K. Antibiotic prophylaxis is suggested, since liver dysfunction is
associated to diminished immune competence. Liver disease may result in alterations in the
metabolism of certain drugs. The physician treating the patient therefore should be consulted in
order to establish which drugs are used, their doses and possible interactions. The administration of
certain analgesics, antibiotics and local anesthetics is generally well tolerated by patients with mild
to moderate liver dysfunction, though modifications may prove necessary in individuals with
advanced stage liver disease. In this context, drugs metabolized in the liver may have to be used
with caution or their doses reduced and certain substances such as erythromycin, metronidazole or
tetracyclines must be avoided entirely. (Table 23).

Puncture/Cut Mucosal surface contact

1. Careful washing of the wound, without
rubbing, for several minutes with soap and water
or a disinfectant.
2. Pressure applied beneath the level of the
wound to induce bleeding
Abundant irrigation with water or saline solution
for several minutes.
Abundant irrigation with water or saline solution
for several minutes.

Table 21. Procedure to be followed after accidental exposure to infected blood, Source: Cruz-
Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. 11

96
 Test Normal values
Bleeding time 1-3 minutes
Prothrombin time 11-15 seconds
Thrombin time 15-20 seconds
Thromboplastin time 25-35 seconds
Platelet count 150.000-400.000/mm3
< 50.000/mm3 : bleeding
INR 0,9-1,1

Table 22. Normal coagulation test values, Source: Cruz-Pamplona M, Margaix-Muñoz M,

Sarrión-Pérez MG. 11

Local anesthetics Lidocaine, Prilocaine, Mepivacaine, Bupivacaine

Analgesics Aspirin, Acetaminophen (Paracetamol),
Ibuprofen, Codeine, Meperidine
Sedatives Diazepam, Barbiturates
Antibiotics Erythromycin, Clindamycin, Tetracycline
Antifungals Ketoconazole, Fluconazole

Table 23. Drugs metabolized mainly in the liver, Source: Cruz-Pamplona M, Margaix-Muñoz
M, Sarrión-Pérez MG. 11

Most of the antibiotics prescribed for oral and maxillofacial infections can be used in
patients with chronic liver disease, and in general the beta-lactams can be administered.
Aminoglycosides can increase the risk of liver toxicity in patients with liver disease, and so should
be avoided. The metabolism of clindamycin in turn is prolonged in such patients, and different
studies suggest that it contributes to liver degeneration. Nonsteroidal antiinflammatory drugs
(NSAIDs) should be used with caution or avoided, due to the risk of gastrointestinal bleeding and
gastritis usually associated to liver disease. Prophylaxis can be provided in the form of antacids or
histamine receptor antagonists. Acetaminophen (paracetamol) is to be avoided in patients with
serious liver disease, and aspirin and NSAIDs are not indicated in patients with altered hemostasis.
Local anesthetics are generally safe provided the total dosage does not exceed 7 mg/kg, combined
with epinephrine. Table 24 shows the drugs that are contraindicated and those that can be used with
caution.

97
 DRUGS CONTRAINDICATED RECOMMENDED
Anesthetics Halothane, Thiopentone Isoflurane, Nitrous Oxide, Local
anesthetics
Analgesics Acetylsalicylic acid, Codeine, Nitrous Oxide
Indomethacin, Mefenamic
Acid, Ibuprofen
Antibiotics Tetracycline, Erythromycin, Local anesthetics
Estolate, Metronidazole
CNS depressants Opioids Benzodiazepines
Corticosteroids Prednisone Prednisolone

Table 24. Management of the different drugs in patients with liver disease, Source: Cruz-
Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. 11

Although some of these substances are metabolized in the liver, the doses at which they are
used in dental practice are considered to be acceptable – unless the patient suffers very severe liver
dysfunction. Patients with alcoholic cirrhosis show increased tolerance of anesthetics, sedatives and
hypnotic agents; as a result, the anesthesia doses should be increased. The safety and efficacy of
many drug substances are influenced by concomitant alcohol consumption. Concern is greatest
regarding the effects of combining alcohol and central nervous system depressors, and the complex
effects of alcohol upon the capacity of the liver to metabolize drug substances. Paracetamol
combined with alcohol can prove particularly dangerous, since the metabolism of both substances
involves the same enzyme (isoenzyme CYP2E1 of the P-450 cytochrome system), and care is
required not to prescribe alcohol-containing rinses among patients recovering from alcohol abuse. 11

9. Dental management in stroke patients (Source: Bodnar DC, et al. 5)

Stroke (produced by cerebral haemorrhage or cerebral ischaemia) is a serious neurological
accident, often fatal, due to a sudden interruption of the oxygenated blood supply to the brain. This
is a frequent cause of death (the first one after myocardial infarction and cancer) and, if not fatal, it
can provoke several disabilities, more or less serious: speech deficiency, hemiplegia or paresis,
different forms of paralysis or palsy with diminished or lost sensorial capacity, motor deficiency.
The patients in such a serious medically compromised condition must benefit from a very good
management of the therapeutical approach. The dental practitioner’s main concern is to detect these
individuals, by means of accurate anamnesis, to avoid any accidents or complications as an outcome
of the basic disease (another stroke can occur anytime), to detect the connected specific risk factors
or the systemic anticoagulant medication side effects. The approach should be very careful after the

98
stroke: there will be no dental treatment within the following 6 months. After that, if the treatment is
really necessary, it will be carried out only after temporarily suspending the anticoagulant
medication, taking into consideration the oral cavity complications and the existing disabilities, if
any, with the assistance of the neurologist.
10. Medical management of the stroke patient (Source: Bodnar DC, et al. 5)
The first target in medical approach of cerebral vascular accident is prevention, since the
risk of a stroke increases with 1.5% for every known risk factor. Therefore, it is important to
identify these factors and also the related systemic diseases and biological factors able to increase
the seriousness of the stroke, as well as it is to try to reduce or eliminate them, as much as possible.
In 60-80% of the cases, ischemic stroke is induced by thrombosis of cerebral blood vessels.
Cerebrovascular diseases are related to atheromatosis and cardiac diseases (myocardial infarction,
atrial fibrillation), to other known risk factors among which there are periodontal diseases. (Table
25). Calcified atheromas of the carotid artery can be sometimes revealed by the dentist, examining
the X-ray orthopantomography of elderly or diabetic patients. If attentively and appropriately
examined, this can be a warning about the risk of stroke. Specific therapy during stroke is vital and
aims at keeping patients alive during and immediately after the attack. This is neurologists’ attribute
and it must also take into consideration the prevention of a second stroke by prescribing appropriate
treatment.
Risk factors Related systemic diseases Biological factors
High blood pressure, Diabetes Coronary diseases, Lower limbs TIA (transient ischemic attack)
melitus, Chronic heavy arterial disease, Migraines in medical history,
smoking, Hyperlipidemia, Asymptomatic carotid stenosis,
Alcoholism, Contraceptive Polyglobulia, Hyperuricemia
medication, Old age, Obesity,
Periodontal diseases

Table 25. Risk factors, related systemic diseases and biological factors able to increase severity
of stroke, Source: Bodnar DC, et al. 5

A patient surviving stroke presents an increased risk of a new episode: for 33.3% of the
patients, it can occur within one month, the risk remains high during the first six months and
decreases to 14% after one year. Fifty percent of patients surviving a stroke present little
disabilities, 15-30% present disabilities that need special care and 10-20% need to be
institutionalised.

99
 DENTAL MANAGEMENT OF THE STROKE PATIENT (Source: Bodnar DC, et al. 5)
A patient with stroke in his record shall get special care during dental treatment:
appointments shall be for choice in the morning, shall be short and without stress. Clinical approach
shall take into consideration several aspects:
- Disabled patients shall be helped by the nurse to sit on dental chair, their airways shall be free and
they shall be accompanied by the persons taking care of them, especially if speech difficulties are
present;
- Anamnesis shall be simple and optimistic, dentist shall stand in front of the patient, without mask,
shall look him in the eyes, shall move slowly and questions shall be simple and clear, for plain
answers (yes/no);
- Anamnesis should reveal patient’s risk factors: if the medical record shows high blood pressure,
cardiac diseases, transient vascular accidents, diabetes, dyslipidemia, coronary atheromatosis,
(heavy) smoking, old age, then such a patient is prone to stroke and/or myocardial infarction;
- History of past strokes needs to be elicited: date, seriousness, treatment, disabilities. There are
situations when patient’s speech is not affected, but he cannot realize the extent of the palsy (he is
not aware of it) or situations when a patient with brain injury on his right side is neglecting his left
side of the body;
- Blood pressure and pain should be monitored and under control during the entire intervention.
Emergency dental treatment is allowed six months after stroke, it should be performed carefully, by
neurologist’s advice and some precautions are needed, according to the specific characters of the
stroke:
- If needed, dental treatment produces bleeding (teeth extraction, pulpectomy, subgingival scaling,
periodontal surgery), anticoagulant systemic medication may cause serious haemorrhage, therefore
anticoagulant drugs like heparin should be stopped at least 6-12 hours before treatment. Six hours
after bleeding, when blood clots are built up, heparin systemic treatment can be resumed. If there is
some other anticoagulant medication involved, it should be stopped several hours or days before
bleeding dental treatment, after determining the International Clotting Rate (ICR) and decision
depends on neurologist’s advice.
- The dentist should be ready for emergency intervention in case of local hemorrhage, with
haemostatic medication and cautery, blood pressure should be monitored and oxygen therapy device
is needed in dental office.
- The minimal amount of anaesthetic solutions should be injected, concentration of added
epinephrine should be very low (1:100.000 or 1:200.000). Use of gingival retraction cord soaked
with epinephrine should be avoided.

100
-Metronidazolum and tetracycline should be avoided, since they may affect blood clotting.
-If the patient shows symptoms of stroke, he should get oxygen therapy immediately and should be
referred to a hospital as soon as possible. Patients with transient ischemic attack (TIA) or with
stroke in their medical record have a very complex dental and periodontal pathology. If patients
show minor physical disabilities after stroke, they can present poor oral hygiene. For such patients,
dentists will advise the use of electric toothbrushes, easier to handle, use of dental floss, oral
irrigation and prophylaxis using chlorhexydine and fluoride. Patients with speech and deglutition
disabilities due to paralysis of oro-facial muscles, with loss of sensitivity of the tissues, with flaccid,
multiple pleated and possibly asimmetrically positioned tongue, with dysphagia, may present
accumulation of food residues on teeth, tongue, oral mucosa. They must learn to clean their teeth
and oral cavity using only one hand or to get/accept another person’s help, in order to avoid caries,
periodontitis, halitosis or oral mucosa diseases. Edentulous patients are advised to get fixed
prosthodontic treatment, because of the difficulties of insertion and desinsertion of removable
dentures. 5
According to Bakardjiev A. prophylaxis includs usage of anaesthetic without
vasoconstrictors. In patients with chronic hypertension is necessary to conduct adequate
hypotensive therapy. 4

11. Dental management of the head and neck cancer patient treated with
radiation therapy
According to Murdoch-Kinch CA, Zwetchkenbaum S. approximately 36,540 new cases of
oral cavity and pharyngeal cancer will be diagnosed in the USA; more than 7,880 people will die of
17
this disease. The vast majority of these cancers are squamous cell carcinomas. Most cases are
diagnosed at an advanced stage: 62 percent have regional or distant spread at the time of diagnosis.
The five-year survival for all stages combined is 61 percent. Localized tumors (Stage I and II) can
usually be treated surgically, but advanced cancers (Stage III and IV) require radiation with or
without chemotherapy as adjunctive or definitive treatment. (Table 26). Therefore, most patients
with oral cavity and pharyngeal cancer receive head and neck radiation therapy (RT) as part of their
treatment. The oral complications of head and neck RT result from radiation injury to the salivary
glands, oral mucosa and taste buds, oral musculature, alveolar bone, and skin. They are clinically
manifested by xerostomia, oral mucositis, dental caries, accelerated periodontal disease, taste loss,
oral infection, trismus, and radiation dermatitis. Some of these effects are acute and reversible
(mucositis, taste loss, oral infections and xerostomia) while others are chronic (xerostomia, dental

101
caries, accelerated periodontal disease, trismus, and osteoradionecrosis.) Chemotherapeutic agents
may be administered as an adjunct to RT. Patients treated with multimodality chemotherapy and RT
may be at greater risk for oral mucositis and secondary oral infections such as candidiasis. The oral
complications of therapy for head and neck cancer can significantly impair quality of life.

Stage Tumor Nodes Distant Metastases

0 Tis N0 M0
I T1 N0 M0
II T2 N0 M0
III T3 N0 M0
III T1 N1 M0
III T2 N1 M0
IVA T4 N0 M0
IVA T4 N1 M0
IVA Any T N2 M0
IVB Any T N3 M0
IVC Any T Any N M1

Tis : in situ, T1 : < 2 cm, T2 : > 2 cm and < 4 cm, T3 : > 4 cm, T4 : Invades adjacent structures
N0 : No nodal involvement, N1 : Ipsilateral, < 3 cm, N2a: Ipsilateral > 3 cm and < 6 cm, N2b:
Ipsilateral, multiple, < 6 cm, N2c: Bilateral/contralateral, < 6 cm, N3 : > 6 cm
M0 : No metastases, M1 : Distant metastases

Table 26. TNM Staging for Head-and-Neck Cancer, Source: Murdoch-Kinch CA,
Zwetchkenbaum S. 17

The oral health care team serves a vital role in the prevention and management of short- and
long-term oral complications of cancer treatment. Hospital-based dentists specially trained in oral
oncology treat some of these patients, but currently in North America most long-term dental care is
provided by general dentists in private practice. Depending on available health care resources, the
patient may rely on his local dentist for pre-treatment oral care and supportive care during cancer
treatment, as well as continued oral health care to manage the long-term oral complications of
cancer therapy. It is essential that all health professionals caring for the cancer patient be
knowledgeable about the diagnosis, prevention and management of oral complications of therapy

102
and their sequelae, in order to work together as a team to minimize the impact of these toxicities on
the patient’s life.
The oral health care team serves a vital role in the prevention and management of short- and long-
term oral complications of cancer treatment. Hospital-based dentists specially trained in oral
oncology treat some of these patients, but currently in North America most long-term dental care is
provided by general dentists in private practice. Depending on available health care resources, the
patient may rely on his local dentist for pre-treatment oral care and supportive care during cancer
treatment, as well as continued oral health care to manage the long-term oral complications of
cancer therapy. It is essential that all health professionals caring for the cancer patient be
knowledgeable about the diagnosis, prevention and management of oral complications of therapy
and their sequelae, in order to work together as a team to minimize the impact of these toxicities on
the patient’s life.

12. Oral Complications of Head and Neck RT (Source: Murdoch-Kinch CA,

Zwetchkenbaum S. 17)

a. Xerostomia and salivary gland hypofunction (Source: Murdoch-Kinch CA,

Zwetchkenbaum S. 17): Xerostomia is the most common oral complication of head and neck RT. In
fact, up to 64 percent of patients treated with conventional head and neck RT still experience a
moderate to severe degree of permanent xerostomia when assessed up to 22 years after radiation
therapy. The most severe complaints occur in patients treated for cancer of the nasopharynx and
oropharynx, most likely due to the close proximity of the field to the parotid glands. Paradoxically,
for such highly differentiated tissues, salivary glands are very sensitive to radiation. There is a sharp
decrease in the salivary flow rate during the first week of RT with conventional fractionation (2
Gy/day). The decrease in flow rate continues throughout the treatment period, especially when both
parotids are irradiated.This correlates to the dose and duration of RT. There is immediate serous cell
death accompanied by inflammatory cell infiltration, and then continuous reduction of salivary flow
rates. Patients often complain of thick, ropy saliva and a sensation that there is too much saliva
because it is difficult to swallow. The exact mechanism of radiation-induced damage to the salivary
glands is not currently well understood. With conventional RT, xerostomia is permanent. Salivary
gland-sparing techniques using intensity modulated radiation therapy (IMRT) have been pioneered
at the University of Michigan. IMRT is rapidly emerging as the standard of care for head and neck
cancer. Salivary gland-sparing IMRT is associated with gradual recovery of salivary flow over time,
and improved quality of life as compared to conventional RT. Residual salivary flow can be

103
stimulated by sialogogues such as pilocarpine or cevimeline, and/or use of sugarless gum and
buffered citric acid tablets (NumoisynTM, Align Pharmaceutical, Berkeley Heights, N.J.) Salivary
substitutes provide transient symptomatic relief.
b. Radiation mucositis (Source: Murdoch-Kinch CA, Zwetchkenbaum S. 17): Mucositis is
an important common acute short-term complication of head and neck RT. It is a dose-limiting
toxicity and may be more severe in patients receiving multimodality therapy for head and neck
cancer. It is characterized by ulceration in the oro-esophageal and gastrointestinal mucosa, resulting
in significant pain and dysphagia. Mucositis initially presents clinically as erythema after 4-5 days
of therapy, corresponding to cumulative doses of 10 Gy to the head and neck. The patient often
complains of oral burning or intolerance to spicy food. As the mucositis progresses after cumulative
radiation doses of 30 Gy (approximately two weeks), ulcers develop. (Figure 6). Radiation-induced
mucositis can involve any radiation-exposed area, including the hard palate. It may be worse in
tissue in direct contact with metallic restorations. Radiation-induced mucositis peaks at two weeks
post RT of 60-70 Gy. This ulcerative phase may last for up to 5-7 weeks following RT, with gradual
healing. Chronic mucositis is a rare occurrence following RT. Mucositis has a significant health and
economic impact on cancer patients. It is one of the most common reasons for a break in the
administration of RT. Measures specifically designed to prevent and treat oral mucositis can be
provided by the patient’s oncology team. The dentist can assist by providing basic oral care
consisting of patient education, disease control, and oral hygiene instruction. These measures can
decrease the microbial load in the oral cavity and prevent other complications associated with
therapy. In addition, patients who have heavily restored teeth may benefit from the use of silicone
mucosal guards worn during RT to reduce the severity of mucositis associated with scatter of
radiation off metal restorations. (Figure 7).

104
 Figure 6. Xerostomia and radiation mucositis in patient one month after the end of
radiotherapy. Saliva is thick and sticky. Mucositis is painful and interferes with eating,
Source: Murdoch-Kinch CA, Zwetchkenbaum S. 17

Figure 7. Silicone mucosal guards. These custom-made guards cover metallic restorations
with 5 mm of silicone impression material, to prevent heating of the metal and backscatter of
radiation in contact with the mucosa, Source: Murdoch-Kinch CA, Zwetchkenbaum S. 17

c. Oropharyngeal candidiasis (OPC): According to Murdoch-Kinch CA,

Zwetchkenbaum S. this is a very frequent complication of cancer therapy; up to 27 percent of
17
patients undergoing RT present with evidence of OPC. It may present as a pseudomembranous
candidiasis (thrush), with thick white plaques that wipe off or as generalized erythema and burning
discomfort. (Figure 8). Clotrimazole has been shown to be more effective than nystatin for
treatment of OPC; clotrimazole 10 mg troches administered five times per day are effective in
treating mild to moderate OPC.38 Some topical preparations have a high sucrose content that may
contribute to caries risk in the xerostomic patient. Fluconazole 50-100 mg daily has been associated
with clinical recovery in 80 percent of patients within 10 days, or within five days with 200 mg
daily. Complete mycologic cure is difficult to achieve. Resistance to fluconazole is associated with
non-albicans yeast such as Candida glabrata and C. krusei. A recent systematic review of this topic

105
failed to find strong enough evidence to support one drug over another in the treatment of OPC in
this population. Although initially encountered during RT, it also can present a long-term problem in
patients with xerostomia. Antifungal prophylaxis may be beneficial in high-risk patients; the
oncology team should make this decision.

Figure 8. Oral candidiasis in a head-and-neck cancer patient six months post-radiotherapy.

These white plaques on the tongue dorsum could be wiped off. This infection responded to
Nystatin suspension, Source: Murdoch-Kinch CA, Zwetchkenbaum S. 17

17
d. Dental caries (Source: Murdoch-Kinch CA, Zwetchkenbaum S. ): After standard RT
there is a profound shift in the oral microflora to a predominance of acidogenic microbes, primarily
Streptococcus mutans and lactobacilli, coincident with a decrease in salivary flow, and an increase
in caries risk. Dental caries in irradiated patients may develop rapidly, as early as three months after
RT. Lesions typically involve the cervical portions of the teeth (Figure 9); however, caries may
affect any tooth surface, including those typically resistant to dental caries such as the incisal edges
of the mandibular incisors. Prevention and treatment of dental caries. A strict daily oral hygiene
regimen that includes fluoride and meticulous plaque removal has been shown to prevent the
development of caries. Chlorhexidine gel has also been shown to clinically reduce caries risk by
lowering mutans streptococci and lactobacilli counts in patients undergoing RT. Chlorhexidine gel
is not currently available in the U.S.; however, chlorhexidine mouthrinse could provide similar
benefits. Alcohol-free formulations should be selected to reduce discomfort in patients with dry
mouth. Caries lesions should be restored before RT to prevent progression of disease and reduce
microbial load. Also, the patient will be more comfortable during treatment if the oral mucosa is
intact. Patients should also receive diet counseling about cariogenic foods and their deleterious

106
effects on the dentition.

Figure 9. Rampant dental caries post-radiotherapy, Source: Murdoch-Kinch CA,

Zwetchkenbaum S. 17

In patients receiving parotid-sparing IMRT, where salivary output has been shown to
increase over time and in patients receiving amifostine during RT, evidence suggests that caries risk
may be reduced. Amifostine is a radioprotective drug that has been shown to have a significant
protective effect on the salivary glands and oral health. In the past, controversy has surrounded this
drug because of two potential problems: tumor protection and toxic side effects. Nevertheless,
amifostine is increasingly being added to many chemoradiation (CRT) protocols to protect the
salivary glands. If so, these new types of RT may allow modification of current caries prevention
recommendations. Further research is needed to investigate modification to current guidelines for
these new treatment modalities.
e. Periodontal disease (Source: Murdoch-Kinch CA, Zwetchkenbaum S. 17): RT effects on
periodontal health include direct effects on the periodontium, and indirect effects associated with
changes in the oral microflora caused by radiation-induced xerostomia. Two potential problems
result: accelerated periodontal attachment loss and increased risk for osteoradionecrosis (ORN)
associated with periodontal disease. RT causes changes in both bone and soft tissue that can
produce hypovascular, hypocellular and hypoxic bone. This reduces the capacity of the affected
bone to remodel and, depending on the dose, may increase the risk of infection, which can lead to
osteoradionecrosis, discussed in the next section.
It is well-established that periodontal involvement of teeth in high-dose irradiated sites can produce
osteoradionecrosis. Extractions in irradiated bone may increase risk for ORN but pre-irradiation
extraction of teeth carries a lower risk of ORN than extractions following RT. Periodontal treatment,
including periodontal surgery, is possible within irradiated sites.

107
 Prevention of periodontal disease and attachment loss: Optimal oral hygiene must be
maintained because of the lowered biological potential for healing of the periodontium after
radiation therapy. The risk for developing ORN is reduced in patients who receive topical fluoride
applications and maintain good oral hygiene because they are less likely to develop caries,
periodontal disease and their sequelae.These measures help to reduce the likelihood of rampant
periodontal destruction that occurs in the absence of good oral hygiene, especially within high-dose
irradiated sites.
f. Osteoradionecrosis (ORN): According to Murdoch-Kinch CA, Zwetchkenbaum S.
ORN is caused by the hypoxic, hypocellular, hypovascular deterioration of bone that has been
17
irradiated. Marx has proposed that this results from the radiation-induced deficient cellular
turnover and collagen synthesis in a hypoxic, hypovascular and hypocellular environment in which
tissue breakdown exceeds the repair capabilities of the wounded tissue. Clinically, ORN may
initially present as bone lysis under intact gingiva and mucosa (type I). This process is self-limiting
because the damaged bone sequestrates, then is shed with subsequent healing. If the soft tissue
breaks down, the bone becomes exposed to saliva and secondary contamination occurs. Sepsis may
also be introduced by dental extraction or surgery, producing a more aggressive form (type II)
(Figure 10). This progressive form may produce severe pain or fracture, and require extensive
resection. The reported incidence of ORN varies widely depending on the institution, type of RT,
and follow-up time. The reported incidence of ORN ranges from 0.92 percent of all head and neck
cancer patients receiving RT to 2.59 percent of patients receiving post-irradiation extractions. 17 The
mandible is affected more commonly, because lower jaw characterized by a relatively poor blood
supply. 19

Figure 10. Osteoradionecrosis in the right posterior mandible, five years post-radiotherapy

108
 and after hyperbaric oxygen therapy. This female patient received chemoradiotherapy for
squamous cell carcinoma of the right tongue base, and within a few months developed
permanent xerostomia and rampant dental caries. Reportedly, daily fluoride and preventive
dental treatment had not been implemented. Pain and infection ensued and led to extraction
of molars on this side. This asymptomatic lesion consisting of exposed bone was unchanged
since her previous recall, six months prior, Source: Murdoch-Kinch CA, Zwetchkenbaum S. 17

Prevention of ORN: ORN may be prevented by extracting these teeth at least two weeks
before RT: periodontally involved teeth; unerupted teeth with communication with the oral cavity;
third molars with evidence of pathology such as cysts or pericoronitis; and pulpally involved or
nonrestorable teeth. Prevention of dental caries and periodontal disease and their sequelae can
prevent ORN in most cases. If teeth must be extracted after RT, care should be given to use
atraumatic technique, smooth sharp edges of bone, and avoid reflection of the periosteum, if
possible. The risk of dental extraction-related ORN does not appear to decrease over time after RT
17
g. Trismus (Source: Murdoch-Kinch CA, Zwetchkenbaum S. ): Trismus can be a
significant side effect of RT, especially if the lateral pterygoid muscles are in the field. In patients in
whom the pterygoid muscles were irradiated, and not the temporomandibular joint (TMJ), 31
percent experienced trismus. In addition, radiation to the TMJ also was associated with a decrease
in maximum vertical opening. Limited mouth opening can interfere with proper oral hygiene and
dental treatment. Therefore, before RT starts, patients who are at risk for developing trismus should
receive instruction in jaw exercises that will help them maintain maximum mouth opening and jaw
mobility. Tongue blades can be used to gradually increase the mandibular opening. Dynamic bite
opening appliances have also been used. The dentist should measure the patient’s maximum mouth
opening and lateral movements before RT, and reevaluate mandibular opening and function at
follow-up dental visits. For patients who experience reduced mouth opening, the intensity and
frequency of the exercises should increase, and a physical therapy regimen prescribed.
13. Pre-RT Dental Assessment and Treatment
According to Murdoch-Kinch CA, Zwetchkenbaum S. patients scheduled to undergo RT
17
should receive a comprehensive dental assessment before therapy begins. The assessment should
be conducted soon after diagnosis to allow adequate time for wound healing if teeth need to be
extracted. The dentist must understand the basis for RT, the radiation treatment planned (dose,
schedule and fields), and the oral/dental/periodontal status of the patient in order to make
appropriate treatment decisions. Therefore, a consultation with the radiation oncologist and the

109
medical oncologist, if the patient is undergoing chemotherapy, is recommended.
17
Goals of Dental Management (Source: Murdoch-Kinch CA, Zwetchkenbaum S. ): The
dentist caring for a head and neck cancer patient should have clearly defined goals of dental
management during the three phases of treatment:
1. Pretreatment goals
a. eliminate potential sources of infection;
b. counsel patient about short- and long-term complications of cancer therapy;
c. provide preventive care.
2. Goals during cancer therapy
a. provide supportive care for oral mucositis;
b. provide treatment of oral candidiasis;
c. manage xerostomia;
d. prevent trismus.
3. Long-term, post-treatment goals
a. manage xerostomia;
b. prevent and minimize trismus;
c. prevent and treat dental caries;
d. prevent postradiation osteonecrosis (ORN);
e. detect tumor recurrence.
Pre-RT dental treatment planning is imperative to address (Source: Murdoch-Kinch CA,
Zwetchkenbaum S. 17):
1. the limited time to provide dental treatment to the patient, especially if the prognosis for
survival is poor;
2. the risk of ORN in irradiated bone with dental extractions or untreated infection;
3. the increased risk of dental caries in the patient whose radiation field includes major
salivary glands.
Ideally, treatment planning for all patients should include disease control and prevention
phases of care. Prosthetic rehabilitation usually is provided several months after RT. Disease control
includes caries removal and restorations, scaling and prophylaxis, establishing good oral hygiene,
removing overhanging restorations, and replacing defective restorations, especially if irritating the
soft tissues. If deep scaling is needed (pocket depths less than 6 mm) the dentist should allow 14
days healing time before therapy if possible. Ill-fitting dentures should be repaired or replaced. The
placement of soft liners should be avoided because they can be a nidus for candidiasis76 and the

110
surfaces tend to be irregular and irritating.
If teeth are to be retained, the dentist should provide the patient with daily fluoride therapy,
either as 1.1 percent NaF gel in custom dental trays or as 1.1 percent NaF toothpaste to be used
once daily before, during and after RT, for the rest of the patient’s life. Regular dental recalls are
essential to maintain compliance with preventive strategies and detect disease at an early stage. The
dentist should encourage the patient to adopt a non-cariogenic diet. Tooth extraction should be
performed 14 days before radiation or chemotherapy starts. After RT, allow at least three months of
healing time to elapse before providing prostheses in edentulous patients. There appears to be little
evidence to support a longer delay to definitive prosthetic care. During pre-RT extractions, the
dentist should aggressively remove sharp pieces of bone to avoid alveoloplasty later. If the lateral
pterygoid muscles are within the field of radiation and trismus poses a risk, the patient should
receive instruction on mandibular range of motion exercises. After RT, the exercises should be
reassessed and, if necessary, modified. Caries prevention plans may also include the prescription of
pilocarpine or cevemeline to stimulate salivary flow, chewing sugarless gum containing xylitol, and
rinsing with artificial saliva containing calcium and phosphate to encourage remineralization.
Decisions to extract teeth. Formalized dental treatment planning models have been proposed in
which decisions are based on both dental and cancer therapy conditions. The primary decision is
when teeth should be extracted before therapy. Other high risk factors include furcation
involvement, mobility > 2 mm, partially impacted teeth and residual root tips, fully impacted teeth
with “pericoronal pathoses,” poor oral hygiene and low dental awareness or lack of cooperation.
This model also considers malignancy risk factors (MRF). High malignancy risk factors include
radiation dose > 55 Gy, a radiation field that includes molars, teeth that are near the tumor, and if
radiotherapy begins in fewer than 14 days. This decision-making model suggests that teeth
considered as high MRF and high DRF should be removed. However, extraction decisions also
should consider the strategic importance of the teeth, the overall impression of the patient, and the
risk associated with extraction (clinical judgment).
In summary, the decision to extract teeth before RT should consider (Source: Murdoch-
Kinch CA, Zwetchkenbaum S. 17):
1. teeth that are in a high-dose radiation field. Such teeth are non-restorable or may require
significant restorative, periodontal, endodontic, or orthodontic intervention.
2. patients with moderate to severe periodontal disease (pocket depths > 5-6 mm) or with
advanced recession.
The dentist may develop a more aggressive dental treatment plan for the patient with low

111
dental awareness, lack of motivation or cooperation, a poor history of regular dental care treatment,
poor oral hygiene, and evidence of past dental/periodontal disease. The dentist also should consider
factors such as position of teeth, relative importance of such teeth for function, oral hygiene,
potential impact of trismus and limited mouth opening on oral hygiene and dental treatment,
taurodontism, and root anatomy.
Pre-Radiation Therapy Protocol from the University of Michigan Department of Oral and
Maxillofacial Surgery and Hospital Dentistry (Source: Murdoch-Kinch CA, Zwetchkenbaum S.
17
):
1. Patient education, both oral and written
a. Effect on salivary glands
i. Dry mouth strategies
1. Increased hydration
2. Salivary substitutes
3. Salivary stimulation – sugarless chewing gum, pilocarpine, cevimeline
ii. Caries prevention
1. Diet counseling
2. Daily fluoride use
3. Regular frequent dental check-ups

b. Effect on bone in irradiated field

i. Need for pre-RT dental evaluation
1. Consult usually requested by radiation oncology
ii. Need for UMHS contact prior to future extraction or surgery in the irradiated field.
c. Potential for trismus
i. Maintain range of motion
1. Tongue blades
2. Therabite™
3. Dynabite™
2. Patient evaluation and treatment plan
a. Consult should provide adequate information about planned field. If not, contact radiation
oncologist.
i. All head and neck cancer patients at University of Michigan now undergo parotid-sparing IMRT
b. Determine the need for extraction based on periodontal and dental condition, oral hygiene,

112
history of regular dental visits, etc.
c. If time permits and patient wishes, perform extractions at the time; or schedule for future day.
d. Inform radiation oncologist of time required for healing before starting RT.
e. Oral hygiene instructions, other treatment to be scheduled.
3. If indicated in consult, fabricate silicone tooth guards to minimize radiation backscatter.
Consult should indicate if guards should be fabricated in a position with teeth open or closed. If
time is available to trim and smooth the guards, deliver at this time. If not enough time is available,
reschedule the patient.
4. If xerostomia is anticipated, consider fluoride use using toothbrush application or carriers.
If there are multiple missing teeth, the toothbrush technique is preferred. Alginate impressions are
made if carriers are to be made. Schedule patient to return for delivery of these. At this time
prescription can be provided for fluoride.
a. Sodium fluoride dentifrice or gel, OR
b. Stannous fluoride gel
5. Schedule the patient to return in approximately seven weeks, during the last week of
radiation therapy. If the date is not known, advise the patient to schedule this appointment. During
this appointment, reinforce the information provided earlier about caries prevention. Determine
where the patient will be getting his routine dental care.
6. If care is to be provided in private practice, continue to be a resource regarding dental
treatment and information for the patient and his dentist. 17

14. Bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Bisphosphonates (BPs) are stable analogs of pyrophosphate, which are naturally occurring
modulators of bone metabolism and have been synthesized and used since the 19th century but their
in-vitro ability to inhibit the precipitation of calcium phosphate was applied clinically in 1960s.
They are used for the treatment of diseases characterized with a high level of bone resorption
(multiple myeloma, osteolytic bone metastases, Paget's disease of bone, fibrous dysplasia, McCune-
Albright syndrome, hypercalcemia of tumour origin, ets. They feature slow intestinal absorption;
they are excreted by the kydneys and have high affinity to hydroxyapatite crystals.
Definition: Necrosis of the jaw bone, related or unrelated to dental procedures, persisting for more
than six to eight weeks, refractory to conservative treatment, in patients without history of prior
radiotherapy in the affected area, but treated with intravenous amino-containing bisphosphonates
for at least one year, or orally-for a much longer period, for a much longer period, for a general
disease causing bone resorption.

113
BPs associated ONJ is a rare but serious clinical condition caused by antiosteoclastic,
antiangiogenic and anti human endothelial cell proliferation effects of bisphosphonates which
inhibit bone turnover.
Dental management (Source: Bakardjiev A. 4):
1. Patients should receive full dental examinations to determine localization and volume of
bone exposure, adjacent soft tissues, patient complaints;
2. To perform images: radiographs, computed tomography (CT), magnetic resonance imaging
(MRI) scintigraphy;
3. Histopathology is an important tool in anatomical pathology, since accurate diagnosis of
multiple myeloma, metastases and primary neoplastic process with purpose of exclusion;
4. Microbiology tests indicates for fungal and bacterial infection.

4
Medical Therapy (Source: Bakardjiev A. ): antibiotics (Amoxicillin 500 mg/8h,
Metronidazole 250 mg/8h, Clindamycin 300 mg/8h, Azithromycin 250mg daily); antifungals
(Nystatin, Fluconazole); antiviral drugs (Acyclovir, Valacyclovir); antimicrobial rinses (0.12%
Chlorhexidine gluconate)
Surgical Management: surgical debridement of all necrotic bone and tension-free primary
4
closure, smoothing of sharp bony edges, hyperbaric oxygen therapy, ozone therapy.

114
 Summary
In present scientific work are applied:
Technical considerations, antibiotic premedication indications, dental management of the patients
with heart diseases (angina pectoris, acute myocardial infarction (AMI), arrhythmias, heart failure
(HF), arterial hypertension (AHT), prevention of bacterial endocarditis, prophylaxis against total
joint replacement infection); respiratory disorders (chronic obstructive pulmonary disease (COPD),
asthma, pulmonary tuberculosis, obstructive sleep apnea syndrome (OSAS), foreign body
aspiration. Dental management of the patients with bleeding disorders (blood vessel wall
abnormalities, thrombocytopenia, thrombocytopathy, inherited coagulation disorders, anaemia,
leukemia; endocrine disorders (hyperthyroidism, hypоthyroidism, hyperparathyroidism,
hypоparathyroidism, Addison’s disease, hyperadrenocorticism (Cushing’s syndrome), diabetes
mellitus, dental management of the patients with renal diseases (acute renal failure, chronic renal
disease (CRD), on hemodialysis, renal transplant patient; dental considerations in patients with liver
disease (viral hepatitis, alcoholic liver disease, non-alcoholic fatty liver, cirrhosis, hepatocellular
carcinoma). Dental management in stroke patients; dental management of the head and neck cancer
patient treated with radiation therapy, oral complications of head and neck RT (xerostomia and
salivary gland hypofunction, radiation mucositis, oropharyngeal candidiasis (OPC), dental caries,
periodontal disease, osteoradionecrosis (ORN), trismus); bisphosphonate-related osteonecrosis of
the jaw (BRONJ).
The present monograph can't consider to exhaustive. Acknowledgement for her actuality will be
useful information for practical work of dental medicine doctors especially for oral surgeons.

115
 References:

1. Abramson AS. Angina Pectoris – Thoughts on its Management in the Practice of Dentistry.
Anesth Prog 1966; 13(8): 258-260.
2. Alamo SM, Esteve CG, Sarrión Pérez MG. Dental considerations for the patient with renal
disease. J Clin Exp Dent 2011; 3(2): 112-9.
3. Atanasov D. Oral surgery. Textbook of “Dental Medicine“ for Dental Students, Plovdiv,
2011: 235.
4. Bakardjiev A. Oral surgery in dental medicine. Basic principles, methods and surgical
protocols, Plovdiv, 2011: 66, 199-206.
5. Bodnar DC, et al. Dental management in stroke patients. Case Reports. TMJ 2008; 58 (3-
4): 228-235.
6. Burgess J, Meyers AD. Dental management in the medically compromised patient.
http://emedicine.medscape.com/article/2066164-overview
7. Carlos Fabue L, Jiménez Soriano Y, Gracia Sarrión Pérez M. Dental management of
patients with endocrine disorders. J Clin Exp Dent 2010; 2(4): 196-203.
8. Cervero AJ, Bagan JV, Soriano YJ, et al. Dental management in renal failure: Patients on
dialysis. Med Oral Patol Oral Cir Bucal 2008;13(7): 419-26.
9. Claramunt Lozano A, Sarrión Perez MG, Gavaldá Esteve C. Dental considerations in
patients with respiratory problems. J Clin Exp Dent 2011; 3(3): 222-7.
10. Cruz-Pamplona M, Jimenez-Soriano Y, Sarrión-Pérez MG. Dental considerations in
patients with heart disease. J Clin Exp Dent 2011; 3(2): 97-105.
11. Cruz-Pamplona M, Margaix-Muñoz M, Sarrión-Pérez MG. Dental considerations in
patients with liver disease. J Clin Exp Dent 2011; 3(2): 127-34.
12. D'Amato-Palumbo S. Dental management of patients with bleeding disorders. Course
Number: 319.
13. Deliverska EG, Krasteva A. Oral signs of leukemia and dental management – literature data
and case report. J of IMAB 2013; 19(4): 388-391.
14. Ganda K. Tufts OpenCourseWare. Management of the Medically Compromised Dental
Patient – Part I 2006: 2,3, 4.
15. Hupp JR, Ellis E, Tucker MR. Contemporary Oral and Maxillofacial Surgery. Sixth Edition
2008: 316.
16. Kavlakov P, et al. Behaviour management to complications in surgical stomatology,

116
 Plovdiv, 1993: 116.
17. Murdoch-Kinch CA, Zwetchkenbaum S. Dental management of the head and neck cancer
patient treated with radiation therapy. J Mich Dent Assoc 2011; 93: 28-37.
18. Owotade FJ. Dental management of haematologic disorders-anaemia.
http://www.authorstream.com/Presentation/aSGuest127640-1342773-dental-management-
of-haematologic-disorders-anaemia/
19. Sarachev Е, Usunov N. Clinical and topographic anatomy of the maxillofacial area,
Plovdiv, 2001: 16.
20. Ugrinov R. Maxillo-facial and Oral Surgery. Propaedeutics and Clinic, Sofia, 2006: 447.
21. Vernillo AT. Diabetes mellitus: Relevance to dental treatment. Oral Surg, Oral Med, Oral
Pathol, Oral Radiol and Endod 2001; 91(3): 263-270.
22. Waters BG. Providing dental treatment for patients with cardiovascular disease. Ont. Dent
1995; 72(6): 24-32.
23. Dental management of the medically compromised patient. Health & Medicine 2009.
24. Protocols for dental management of the medically compromised patient.
http://dentalclinicmanual.com/docs/medicallycompromisedpatients.pdf

117