RED BLOOD CELL ABNORMALITIES * Areas where vessels are close to the skin surface

(APPROACH TO THE DIAGNOSIS OF ANEMIA)

• Dry, Shriveled skin
ANEMIA • Thinning, loss of luster, premature graying of hair
Reduction below normal in the concentration of • Brittle, lackluster nails, spooning
hemoglobin or RBC’s in the blood
Anemia is not a diagnosis in itself, but merely an objective III. Neuromuscular Signs
sign of disease. •Headache
First step in its diagnosis is detection of its presence. •Vertigo
•Tinnitus
3 FUNCTIONAL CATEGORIES OF THE ANEMIAS
•Faintness
•Disorders of Proliferation •Retinal hemorrhage
•Disorders in Erythrocyte Maturation •Paresthesias
•Disorders due Primarily to Erythrocyte Destruction or Red •Scotomas
Cell Loss •Lack of mental concentration
SUBJECTIVE DATA •Drowsiness
• Severity of the anemia •Restlessness
• Rapidity of onset
• Patient’s age and CV status IV. GI Manifestations
o capacity of the CV & pulmonary system
• to compensate for the anemia
•Glossitis
• Associated manifestations of the underlying disorder •Atrophy of the papillae of the tongue
- Endocrine disorder
- Renal disorder
•Dysphagia
- Hepatic disorder •Oral ulcers
• Onset & Duration of symptoms
•Gingival hyperplasia
insiduous or acute •Hepatosplenomegaly
• Previous prescription for hematinics
& response
• Medication history V. Sternal Tenderness
• Occupation, household customs & Lymphadenopathy
hobbies
• Symptoms of hemolysis Even the most expert clinical appraisal does not supplant
jaundice, changes in urine color accurate measurement of the blood for the detection,
• Symptoms of blood loss quantification and characterization of anemia.
melena, hematochezia, epigastirc pain
Changes in Normal Hemoglobin/Hematocrit Values with
• Obstetric & Gynecologic history Age and Pregnancy
# of pads/day •Age/Sex Hemoglobin g/dl Hematocrit %
duration At birth 17 52
# of pregnancies, abortions - interval Childhood 12 36
• Concomitant bleeding manifestations Adolescence 13 40
• Dietary history Adult man 16(+2) 47(+6)
• Fever, Weight loss Adult woman 13(+2) 40(+6)
(menstruating)
I. Cardiac Signs Adult woman 14(+2) 42(+6)
(postmenopausal)
•Hemic murmurs: mid or holosystolic often in the pulmonic During pregnancy 12(+2) 37(+6)
or apical area, due to increased blood flow and turbulence
•Gallop rhythms Red Cell Indices

•Tachycardia/Cardiomegaly •Index Normal Value

Mean Cell Volume(MCV):
•Strong peripheral pulses with wide pulse pressure (hematocrit x 10)/(red cell ct. x 106) 90 + 8 fL

II. Integumentary Manifestations Mean Cell Hemoglobin (MCH):

(hemoglobin x 10)/ (red cell ct. x 106) 30 + 3 pg
•Pallor: <8 to 10 mg/dL hemoglobin
Affected by: Mean Cell Hemoglobin Concentration:
- state of vasoconstriction/vasodilatation (hemoglobin x 10)/ hematocrit, 33 + 2%
- degree & nature of pigmentation or MCH/MCV
- nature & fluid content of the subcutaneous
tissues VI. Genitourinary Signs
Most constantly detected in:
- mucous membranes of the mouth, pharynx,
• Slight proteinuria
conjunctivae, lips • Changes in urine color
- nailbeds Always rule out primary disease of the GUT.

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Even the most expert clinical appraisal does not
supplant accurate measurement of the blood for the
detection, quantification and characterization of
anemia.

Objective Data Normal bone marrow (HPO)

Laboratory tests:
I. Red cell count- hgb, hct, reticulocyte
count, RBC indices
II. White Blood cell count- diff’l, nuclear
segmentation of neutros
III. Platelet count
IV.Peripheral smear morphology
V. Iron Studies
VI. Bone marrow examination

RETICULOCYTE COUNT ASSESSMENT (Possible Cause of Anemia)

•Normal Value: 0.5 – 1.5% (old) CLASSIFICATION OF ANEMIAS BASED ON ETIOLOGY
5 – 15 x 10-3 (SI) • Increased Blood Loss
Correction:
Acute and Chronic Hemorrhage
Patient’s Hct x Reticulocyte count % = corrected
• Excessive Blood Destruction ((Hemolysis)
45
reticulocyte A. Congenital
1. Red Cell Morphologic Defects
Corrected Reticulocyte = RPI (e.g. Congenital
2 Spherocytosis)
2. Hemoglobinopathies
WHITE BLOOD CELL COUNT (e.g. Thalassemias)
3. Enzyme Defects
•Normal Value: 4.5 – 10.0 x 10 9/L (e.g. G6PD Deficiency)
Percentage Absolute B. Acquired
No. 1. Immune Disorders
Bands 0-0.05 0-0.7 (e.g. LE)
Segmenters 0.50-0.70 1.8- 2. Non-Immune Disorders
7.0 (e.g. Infections, Allergy, etc.)
Lymphocytes 0.20-0.40 1.0-4.8
Monocytes 0-0.07 0- • Marrow production defects
0.80 a. Hematinic deficiencies – iron, Vit.
Eosinophils 0-0.05 0- B12, Folic Acid
0.45 b. Infiltrative Diseases – Leukemias,
Basophils 0-0.01 0-0.20 lymphomas, Cancer
c. Aplasia
Normal Peripheral Smear d. Miscellaneous – Endocrine, Renal,
Infections

CASE STUDIES
•Case 1
Mr. Santos, 48 years old farmer consulted
because of progressive weakness and pallor.
No jaundice nor hepatosplenomegaly on
P.E.
Petechiae noted on both L.E.’s
CBC Result:
Hb: 7 gm/dl
Hct: 21
WBC: 4,000
Normal bone marrow (LPO) lymph: 48%
segs: 52%
Platelet count: 80,000
Reticulocyte Count:5 x 10-3

Bone Marrow: FATTY MARROW

APLASTIC ANEMIA
•A type of hypoproliferative anemia characterized by
pancytopenia with marrow hypocellularity
•Etiology:
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 1. Primary
a. Congenital
•Most common cause of anemia worldwide
Fanconi’s Anemia •Iron is absorbed primarily in the duodenum
b. Idiopathic and upper jejunum
2. Secondary
a. Radiation •Picture : causes of iron anemia
b. Drugs and Chemical
Regular effects
Idiosyncratic effects • Case 3
c. Viruses Mrs. Cruz, 75 year old female consulted
d. Immune diseases because of progressive weakness and loss of balance.
e. PNH She also complains of numbness and tingling sensation
f. Pregnancy in all extremities. She has no gastrointestinal
Pathogenesis: complaints.
• Depletion of hematopoietic cells by an agent or - not a diabetic but is hypertensive
event that kills stem cells - prefers to eat vegetables and fish
• Suppression of proliferation and maturation of stem because of poor dentition
cells by an immunologic or lymphocyte mediated
mechanism P.E.
Patient is pale with smooth, red tongue.
Clinical Features: No organomegaly noted
- symptoms related to decrease RBC, Laboratory Results
WBC, platelets CBC: Hb: 80 g/L WBC: 9 x 109/L
-Physical exam: lymphadenopathy and Hct: .26
MCV: 102fL
seg:
lymph: 20%
74%
splenomegaly not typical
MCH: 36 pg eos: 2%
-Laboratories: Pancytopenia, decrease MCHC: 38% mono: 4%
reticulocyte count platelets: adequate
Bone marrow: fatty marrow
Peripheral Smear: Macrocytes
Management Options:
• Transfusion support MEGALOBLASTIC ANEMIA
• Bone marrow transplantation -disorder caused by impaired DNA synthesis
• Immunosuppression with anti-thymocyte globulin,
with or without steroids -Cell primarily affected: blood cells
• Androgen stimulation GI epithelial cells
-slowed nuclear cell division with normal progression of
•Case 2 cytoplasmic maturation
Megaloblastosis
J.K., 35 year old housewife complains of progressive
easy fatigability of about 3 months duration. Folate sources: mainly fruits and vegetables
Review of System: (-) epigastric pain Cobalamin sources: meat & dairy foods
(-) hematochezia nor
melena Cause: B12 or/& Folate Deficiency
menses – 28 days cycle, 7 days duration,
3 days profuse flow consuming
5-6 fully soaked pads/day Clinical Manifestations:
(-) bruises/ecchymoses
Anemia with slight icteresia
P.E. Pale, no jaundice GI manifestations – glossitis, smooth,
(-) hepatosplenomegaly beefy red tongue, malabsorption
3. Neurologic manifestations (Cobalamin) - subacute
Laboratory results: combined degeneration of CNS
peripheral neuropathy – numbness,
CBC: Hb: 60g/L WBC: 6 x 109/L weakness, ataxia, paresthesia,
Hct: .21 seg: 70% disturbances of mentation
MCV: 80fL lymph: 25%
MCH: 25 pg eos: 3% •Management:
MCHC: 28% mono: 2% 1. Treatment of underlying problem
platelets: adequate 2. Replacement therapy
Reticulocyte count: 1.5 x 10-3 oral folic acid
parenteral B12
Peripheral smear: HYPOCHROMIC

Iron studies:
•Case 4
Ferritin: 8ug/L Mrs. Santos, 50 year old male was referred for
Iron: 10 (N.V.9 - 27 umol/L) evaluation of anemia. She begun to experience easy
TIBC: 60 (N.V. 54 – 64 umol/L) fatigability about 5 weeks PTC. She also noticed
Percent Saturation: 17% passage of highly colored urine.
(+) weight loss of about 5 lbs in the last 2 months
IRON DEFICIENCY ANEMIA (+) febrile episodes

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•P.E. icteric sclerae
(+) cervical lymphadenopathy
(-) hepatomegaly
(+) splenomegaly

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 Splenectormy – for moderate to
CBC: Hb: 70 g/L WBC: 13x 109/L severe hemolysis
Hct: .21 seg: 80% Folic Acid supplementation
MCV: 98fL lymph: 20% APPROACH TO THE BLEEDING PATIENT
MCH: 35pg
MCHC: 36%
platelets: adequate SCREENING HISTORY
•A history taken to evaluate hemostasis should answer
Reticulocyte count: 80 x 10-3/L these questions:
Peripheral smear: spherocytes
Other tests: •Has the patient experienced abnormal bleeding or
Direct Coombs: +++ bruising? If so, are symptoms recently acquired or do they
Peripheral Smear: SPHEROCYTES date back to childhood?
•Is there a history of an acquired disorder that would impair
hemostasis? E.g., chronic liver disease, SLE, uremia or a
IMMUNE HEMOLYSIS hematologic malignancy.
Warm-antibody Immunohemolytic Anemia •Is the patient taking a drug that could interfere with
-induced by IgG or IgM Abs reacting specifically on hemostasis?
antigens on RBC membrane •Have other members of the family bled abnormally?
Diagnosis: (+) Coomb’s test In questioning a parent about significant bleeding in a small
child, one should ask specifically about:
Management:
Steroids
•Bleeding from umbilical stump
Splenectomy •Bleeding after circumcision
Immunosuppresants •Bleeding from cuts in mouth
•Frequency & size of hematomas of scalp
•Case 5 •Extent of bruising from minor trauma, eg. Falls from
JA, 18 year old male consulted because of
recurrent jaundice and pallor. Jaundice was first noted swings or bicycles or down steps
when he was 4 years old. •Nosebleeds that stop w/in mins, even if frequent, suggest
No history of blood transfusions. that hemostasis is N. Prolonged nosebleeds requiring
Family history is positive for another sibling with medical intervention arouse suspicion of impaired
similar problem. hemostasis.
In assessing bleeding history of an adult patient, one
evaluates:
P.E. Icteric sclerae
moderate splenomegaly •Abnormal bruising, ask specific questions:
CBC: Hb: 81 g/L
•How often do you notice a new bruise on your body?
Hct: .30 •Do you develop bruises larger than a 1in dm without
WBC: 11.5 x 109/L remembering how you got the bruise? If so, how big
seg: 75% was the largest of these bruises?
lymph: 24% •Do you notice bruises after injections?
eos: 1%
platelets: adequate •Excessive bleeding from small cuts
Reticulocyte count: 60 x 10-3/L
Peripheral smear: (+) spherocytes •Bleeding after previous surgery
•Bleeding after dental extractions. Bleeding that lasts
HEREDITARY SPHEROCYTOSIS >24h after extraction of a permanent tooth or that starts
-inherited RBC membrane abnormality – autosomal again after 3-4 days is suggestive of a hemostatic
dominant pattern of inheritance abnormality.

-Characterized by spherical RBC due to a molecular defect DRUGS THAT INTERFERE WITH HEMOSTASIS
in one of the proteins of the cytoskeleton of the RBC
membrane
•Aspirin, clopidogrel, dipyridamole
ankrin •Drugs that interfere with blood coagulation: heparin, oral
Protein 3 anticoagulants, (?) herbal medications
Spectrin
PHYSICAL EXAMINATION
Clinical Manifestations:
anemia
•Bleeding into skin and soft tissues
jaundice •Petechiae: characteristic of vessel & platelet problem.
cholelithiasis Usually pinhead size but maybe bigger.
Characteristically develops 7 regress in crops. Most
Diagnosis: spherocytes on smear conspicuous in areas of increased venous pressure.
reticulocytosis Must be distinguised from small telangiectsias &
(-) Coomb’s test angiomas
(+) Osmotic fragility test •Ecchymoses, hematomas: large superficial
hematomas maybe seen in coagulation disorders.
Management: •Palpable purpuras may be seen in vasculitis

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•Hemarthorses – bleeding into synovial joints and virtually
diagnostic of a severe hereditary coagulation disorder. May
develop without discoloration or other external evidence of
bleeding.

•Traumatic bleeding
Response to trauma is an excellent “screening test” for
the presence of hereditary hemorrhagic disorder. A
history of surgical procedures or significant injury w/o
abnormal bleeding is equally good evidence against
presence of such disorder.

•Miscellaneous bleeding manifestations

spontaneous bleeding from body orifices
menorrhagia melena
metrorrhagia epistaxis
hematuria gingival
bleeding
hematemesis hemoptysis
Bleeding into serous cavities & internal fascial spaces
retroperitoneal space
psoas sheath
CNS
retina

CLINICAL DISTINCTION BETWEEN DISORDERS OF

VESSELS & PLATELETS & DISORDERS OF BLOOD
COAGULATION

FINDINGS COAG D/O PLT OR VESSEL D/O

Petechiae Rare Characteristic

Deep dissecting Characteristic Rare

hematomas

Superficial Common, usually Characteristic,

ecchymoses large & solitary usually small &
multiple
Hemarthrosis Characteristic Rare

Delayed bleeding common Rare

Bleeding from minimal Persistent, often

sup. cuts & profuse
scratches
Sex of patient 80-90% of Relatively more
hereditary forms common in F
M
(+) family hx common rare