DEEP VEIN THROMBOSIS

diagnosis & management

R. Mohammad Budiarto
Suryo Ardi Hutomo
INTRODUCTION

• Deep Vein Thrombosis (DVT), along with pulmonary emboli are the
spectrums of venous thromboembolism (VTE).
• VTE itself is the third causes of cardiovascular death worldwide,
after myocardial infarction and stroke
• The clinical manifestations of DVT are usually non-specific make it
difficult to diagnose clinically, so the venous thromboembolism often
undetected make the mortality rate remain high
DEFINITION, EPIDEMIOLOGY, &
PATHOPHYSIOLOGY
SECTION - 1
WHAT IS DEEP VEIN THROMBOSIS ?
■ DVT : development of a blood clot in a major deep vein in the leg, thigh, pelvis, or
abdomen, which may result in impaired venous blood flow and consequent leg
swelling and pain

(Vascular Medicine: A Companion to Braundwald’s Heart Disease, 2013)

EPIDEMIOLOGY

■ Venous thromboembolism, which includes DVT and PE,

represent the third most common cause of cardiovascular
death after myocardial infarction (MI) and strokes
■ VTE occurs in about 1 person per 1000 each year in the
United States
■ one third of patients with symptomatic VTE present with
PE; the remainder present with DVT alone
PATHOPHYSIOLOGY
PATHOPHYSIOLOGY
-Stasis disrupts laminar flow  platelets contact with endothelium  coagulation factors
accumulate and retards the influx of clotting inhibitors.
-Hypercoagulable State e.g inherited deficiencies of antithrombin, protein C, and protein S,
cancer/neoplastic diseases
-Vascular damage can denude the endothelium  expose subendothelial collagen, as a
substrate for the binding of von Willebrand factor and platelets  initiates the clotting
cascade, leading to clot formation.
STASIS INCREASED COAGULABILITY VASCULAR DAMAGE
e.g: immobilization, heart failure e.g: thrombophilia, cancer e.g: surgery, trauma

ACTIVATION OF COAGULATION CASCADE

+ disrupted coagulation-fibrinolysis balance

Blood clot (red thrombus)

(Lilly, Pathophysioloy of Heart Disease, 2013)
SECTION - 2
 Clinical manifestation of DVT

• Asymptomatic
• Calf or thigh discomfort
particularly when standing or
walking
• Unilateral leg swelling
• Signs : Edema, Localized
warmth and erythema, (Homans’ sign)
Tenderness, calf pain
produced by dorsiflexion of the
foot (Homans’ sign)
Severe presentation of DVT
Phlegmasia caerulea dolens :

DVT in major deep veins + collateral veins

Massive Edema

Arterial flow Venous drainage

compromised compromised

Pulseless, Cyanosed extrimities

Phlegmasia alba dolens :

DVT in major deep veins
collateral veins are spared
Massive Edema
Venous drainage
still present
Arterial flow compromised

Pale extrimities

(Phlegmasia Alba and Cerulea Dolens, 2017)

 Diagnostic Approach
WELLS SCORE

(Diagnosis and management of acute deep vein thrombosis, European Society of Cardiology, 2017)
 Additional Examination

D-DIMER
• A plasmin-derived degradation product of cross-linked fibrin,
• D-dimer can be measured in whole blood or plasma to provide an indirect
index of ongoing activation of the coagulation system.
• D-dimer examination can be done with ELISA or latex agglutination assay. D-
dimer <0.5 mg/mL can exclude DVT diagnosis.
• D-dimer is sensitive but not specific, so negative results are useful for DVT
exclusion, whereas positive values ​are not specific to DVT, so they can not
used as a single test for DVT diagnosis
 Additional Examination
DUPLEX ULTRASOUND
- first line DVT imaging modality
- sensitivity 94.2% for proximal DVT, and 63.5% for isolated distal DVT
- specificity 93.8%

(Myers et al, 2004)


VENOGRAPHY
Invasive Venography
• the gold standard for diagnosing DVT
• the test is rarely performed in many centers
• Uncomfortable and may be complicated by
hypersensitivity reactions or superficial
phlebitis
Additional Examination
CT / MR Venography
• capability of showing additional
abdominal, pelvic, and chest pathology
that may be etiologically associated with
the development of venous thrombosis,
such as pelvic masses or abdominal or
thoracic malignancies
Management of
deep vein thrombosis
SECTION - 3
ACUTE PHASE DVT MANAGEMENT

GOALS
Stopping the increase of TREATMENT
thrombus
ANTICOAGULATION
Limiting the leg swelling
progressive
REPERFUSION TREATMENT
• FIBRINOLYSIS
To lytic and remove the blood clot and • MECHANICAL
prevent venous dysfunction or the
occurrence of post-thrombosis syndrome
VENA CAVA FILTERS
Prevent the occurrence of
embolism
COMPRESSION STOCKINGS
ANTICOAGULATION
• Anticoagulation is the mainstay treatment of deep vein thrombosis
• early anticoagulation  to stop thrombus propagation, minimize the risk of embolization,
and minimize the risk of early and late recurrent DVT.
• long-term anticoagulation  to reduce recurrence

PARENTERAL ANTICOAGULANT ORAL ANTICOAGULANT

Unfractionated Heparin (UFH) Warfarin

Low-Molecular Weight Heparin: NOACs (Rivaroxaban,
Enoxaparin Dabigatran, Apixaban,
Edoxaban)
Fondaparinux
Parenteral Anticoagulant

Fondaparinux
Low-molecular weight heparin

UFH
 Anticoagulation

Parenteral Anticoagulant
Unfractionated Heparin (UFH)
• mechanism of action :
1). improve antithrombin III as a
clotting factor inhibitor, and
2). releases tissue factor pathway
inhibitor (TFPI) from the blood vessel
wall.
• UFH therapy is based-weight and
dose are titrated accordingly value
of Activated Partial
Thromboplastin Time (APTT).
• Dosage: bolus of 80 IU / kgBB i.v,
followed by infusion of 18 IU /
kgBB / hour.
• The desired APTT value is 1.5- 2.5
controls.
(Handbook of Patient Care in Vascular Diseases, 2008)
 Anticoagulation

Parenteral Anticoagulant
Low Molecular Weight Heparin

LMWH has been proven in clinical trials to be equally effective as UFH in

the treatment of DVT.

LMWHs have several advantages over UFH :

• Their bioavailability is better due to lesser plasma protein binding.
• The dosage is a convenient once or twice per day, subcutaneously,
outpatient treatment is possible
• LMWHs are weight-based and do not need monitoring
• LMWHs act more specifically on factor Xa, rather than thrombin, which may
lessen the risk of bleeding.
• The incidence of heparin-induced thrombocytopenia with LMWH is ten times
less than with unfractionated heparins

Enoxaparin dosage for the treatment of DVT : 1 mg /kg twice daily or 1.5 mg / kg
once daily

(Handbook of Patient Care in Vascular Diseases, 2008)

Oral Anticoagulant

Warfarin

Warfarin

Warfarin Rivaroxaban, Apixaban, Edoxaban

Warfarin Dabigatran
 Anticoagulation

Oral Anticoagulants
Warfarin

inhibits coagulation by inhibiting liver synthesis of vitamin K–

dependent clotting factors (II, VII, IX, X)

Warfarin have long half-lives (20-60 hrs), anticoagulation requires

several days (2-5 days) of therapy before the patient is
anticoagulated

Oral anticoagulation with warfarin is started during heparin

therapy and is continued for 3 to 6 months

Target INR  2.0 to 3.0 for at least two days before stopping the
heparin

(Handbook of Patient Care in Vascular Diseases, 2008)

 Anticoagulation

Oral Anticoagulants
New Oral Anti Coagulants (NOACs)
-Risk reduction for recurrent VTE with all of the NOACs are similar with VKA
-Bleeding risk of NOACs are less than VKA

(Antithrombotic Therapy for VTE Disease, CHEST Guideline and Expert Panel Report, 2016)
 Anticoagulation

Anticoagulation course of treatment

Long Term
Initial Treatment Treatment Extended
(first 5-21 days) Treatment
(first 3-6 months)

-Use parenteral anticoagulant (heparin or

LMWH), precedes oral anticoagulant
-Recommended duration- ofindividually
treatment :tailored
3
-Except rivaroxaban andmonths
Apixaban(minimum)
-Warfarin  overlapping -Using
with iv anticoagulant - balanced against bleeding
oral anticoagulant risk
- Patient’ preferences

(Diagnosis and management of acute deep vein thrombosis, European Society of Cardiology, 2017)
 Anticoagulation

Extended Treatment?
-Decision to discontinue or not anticoagulation should be individually tailored
and balanced against bleeding risk, taking into account patients’ preferences

-Clinical prediction rules have been derived and prospectively validated to

detect low-recurrence risk patients.

HERDOO-2
Vienna Prediction Model

(Diagnosis and management of acute deep vein thrombosis, European Society of Cardiology, 2017)
Extended Treatment?
NO. CONDITIONS
1 DVT + Cancer
2 Recurrent DVT
3 Provoke DVT (unless Cancer)
e.g surgery, travel,
immobilization etc.
4 DVT + Pregnancy
5 Distal DVT
6 Unprovoked Proximal DVT
DURATION OF ANTICOAGULATION
Indefinite therapy (until cancer inactive)
Indefinite therapy
3 month therapy
Pregnancy period + 12 weeks postpartum
3 month therapy
Risk/Benefit Consideration
Extended Treatment?
Consideration for Unprovoked DVT
Factors favouring extension Factors favouring cessation

-Extensive first event -Bleeding complications

-Patient preference -High Bleeding risk*
-Good anticoagulant control -Diagnostic uncertainty
-Presence of Moderate/severe PTS -Isolated subsegmental PE
-Presence/ suspicion of Pulmonary HT -Patient preference
-Persistent risk factors e.g Obesity -Poor adherence
*High risk if >= 2 of the following Age > 65, previous bleeding, renal failure, liver failure,
thrombocytopenia, previous stroke, diabetes, anemia, antiplatelet therapy, poor
anticoagulant control, comorbidity with reduce functional capacity, recent surgery, alcohol
abuse
REPERFUSION TREATMENT
• to normalize venous circulation, preserve venous valves, preserve the limb and
prevent post-thrombotic syndrome

• Options include endovascular thrombus removal (catheter-directed

thrombolysis), pharmaco-mechanical thrombolysis & surgical thrombectomy

• Systemic fibrinolytic therapy is rarely effective thus are not recommended.

• Indications: selected patients with iliofemoral DVT, phlegmasia cerulea dolens

Catheter-directed thrombolysis Mechanical thrombectomy

Catheter-Directed Thrombolysis
Catheter-directed thrombolysis (CDT) : infusion of a thrombolytic agent directly
into the venous thrombus via a multiple–side-hole catheter with the use of
imaging guidance.

Multiple-side hole catheter

Streptokinase, Urokinase,
r-TPA

Vein thrombus

Fibrinolytic agent
Catheter-Directed Thrombolysis

(Pharmacomechanical Catheter-Directed Thrombolysis for Deep-Vein Thrombosis,2017)

-iliofemoral DVT,
-symptoms for <14 days,
-good functional status,
-life expectancy of > 1 year, and
-a low risk of bleeding

(Antithrombotic Therapy for VTE Disease, CHEST

Guideline and Expert Panel Report, 2016)
VENA CAVA FILTER
• To prevent pulmonary emboli in DVT pts
• permanent filters can be associated with long-
term complications (inferior vena cava
occlusion), recurrent DVT, and post-thrombotic
syndrome
• Vena Cava filters should be restricted to patients
who have high risk for recurrent PE and an
absolute contraindication for anticoagulation
• No Benefit in patients with acute DVT or PE who
are treated with anticoagulants

(Antithrombotic Therapy for VTE Disease, CHEST

Guideline and Expert Panel Report, 2016)
COMPRESSION STOCKINGS

• Goal of compression is to relieve venous

symptoms and eventually prevent PTS.
• Guidelines  routine use are not recommended
• Although role of stockings in PTS prevention may
be uncertain, their use remains a reasonable
option for controlling symptoms of acute proximal
DVT

(Antithrombotic Therapy for VTE Disease, CHEST

Guideline and Expert Panel Report, 2016)
COMPLICATIONS OF
DEEP VEIN THROMBOSIS
SECTION - 4
COMPLICATIONS
1. POST-THROMBOTIC SYNDROME

-Major complication of DVT

-Incidence 20-40%
-Caused by chronic obstruction of
venous outflow and/or destruction of
venous valves, resulting in venous
hypertension from venous insufficiency
and/or venous outflow obstruction
COMPLICATIONS
2. PULMONARY EMBOLI
-Acute PE is the most serious clinical
presentation of VTE, most cases are the
consequence of DVT.
-Clinical Presentation : Chest pain, Dyspnea,
Hypotension, Hypoxemia
-Diagnosis : Wells Score, CT Angiography,
Echo, D-Dimer,
-Treatment: resuscitation, fibrinolysis,
anticoagulation, surgical/intervention

(Guidelines on the diagnosis and management of acute pulmonary embolism, ESC, 2014)
SUMMARY
• Deep Vein Thrombosis (DVT), are the spectrums of venous
thromboembolism  third causes of cardiovascular death
• Clinical manifestation are not sensitive nor specific
• Duplex Ultrasound are the 1st line diagnostic modality for DVT
• Anticoagulation are the mainstay treatment
• Reperfusion treatment are indicated in limb-threatening DVT only
• Vena cava filters are used for patients with CI of anticoagulant
• Compression stockings are useful to reduced the symptoms of
venous stasis
• Major complication of DVT are Post Thrombotic Syndrome and
Pulmonary Emboli