Pathophysiology of Venous Thromboembolism

Secondary Hemostasis

Begins simultaneously with platelet plug formation - Process is slower (~minutes)

Initiated by internal and/or external vessel injury - platelets enhance activation of coagulation system which release and concentrate clotting factors and provide surface for clotting factors to assemble

Termed the “coagulation cascade”

Coagulation Cascade

Intrinsic Pathway

Extrinsic pathway

Common pathway

Fibrinolytic system

Virchow’s triad - Etiology

Thombosis is caused by 3 factors that enhance eachother:

Endothelial injury

Abnormal Blood flow - “stasis”

Hypercoagulability

Risk Factors for VTE

Age >40 Acquired (A)

History of VTE (A)

Risk Factors for VTE - Abnormal Blood Flow

Acute medical illness requiring hospitalization (T - transient)

Immobility (A/T)

Obesity (A/T)

Risk Factors for VTE - Endothelial Injury

Major orthopedic surgery (T)

Trauma (T)

Indwelling venous catheters (T)

Hypercoagulability

Malignancy (A)

Antiphospholipid antibodies (A)

Pregnancy (T)

Hormone therapy (T)

Protein C/S deficiency (I - inherited)

Antithrombin III deficiency (I)

Factor V Leiden (I)

Factor VIII/XI excess (I)

Deep Vein Thrombosis (DVT): Clinical Presentation

Signs/Symptoms - Leg edema, usually unilateral

Warmth, erythema/discoloration

Local tenderness or pain

Palpable cord

Homan’s sign

Some patients may be asymptomatic

Location of signs/symptoms may not be at location of thrombus

Pulmonary Embolism: Clinical Presentation

Chest Pain

Dyspnea

Tachypnea

Tachycardia

Hemoptysis

other s/s: cough/wheezing, calf/thigh pain, diaphoresis, fever, hypotension

Severe: cardiovascular collapse

Diagnosis of VTE: Overview

Patient scoring system - Well’s Score

Laboratory Marker - D-dimer

Diagnostic Imaging - DVT: Compression ultrasound (CUS) or venography

PE: computerized tomography pulmonary angiography (CTPA) or ventilation-perfusion (V/Q) scan

Hypercoagulable work-up

D-Dimer

Clot degradation product formed when cross-linked fibrin is lysed by plasmin

Levels are significantly elevated in patients with acute VTE - Reference “normal” value for most assays is <500 ng/mL

However, many non-VTE conditions associated with inc. d-dimer - Surgery/trauma, advanced age, pregnancy, cancer, etc.

Useful adjunctive test for patients with questionable VTE

An elevated (+) D-dimer, by itself, is not diagnostic for VTE

A normal (-) D-dimer can “rule out” an active thrombosis

Diagnostic Imaging for DVT: Compression Ultrasound

A probe placed on the skin uses soundwaves to visualize veins in the lower extremity

Pros: Non-invasive, Inexpensive, Can be performed at bedside, Sensitive to detect large thrombi that occlude proximal veins

Cons: Relatively insensitive to smaller, non-occlusive thrombi and calf vein thrombosis

First-line diagnostic test for DVT

Diagnostic Imaging DVT: Venography

Contrast dye is injected into the peripheral veins, providing visualization of the lower extremity venous system

Pros: Most definitive test to assess for thrombosis within the veins (“gold standard”)

Cons: Invasive (IV contrast), Expensive, Contrast may cause adverse effects

Rarely used in clinical practice

DVT Well’s Criteria

≤0 Low/unlikely 5%

1-2 Moderate 17%

≥3 High/likely 17-53%

PE Well’s Criteria

≤4 PE unlikely (rule out with D- Dimer)

≥5 PE likely (confirm with CT)

Diagnostic Imaging PE: Computerized Tomography Pulmonary Angiography (CTPA)

Uses CT scanning technology and contrast dye to visualize the pulmonary arteries

Pros: Increased sensitivity to detect emboli in smaller vessels, More widely available

Cons: Invasive (IV contrast), Higher doses of radiation (5x V/Q)

First-line diagnostic test in most patients

Diagnostic Imaging PE: Ventilation-Perfusion (V/Q) Scan

Radioactive tracers are inhaled (ventilation) then injected (perfusion) and a gamma camera visualizes airflow; mismatches (V>Q) indicate a blockage

Pros: Lower doses of radiation, No absolute contraindications

Cons: Invasive (radioactive tracer), Not widely available

Usually reserved for pregnant patients or those with contraindication to CTPA (e.g., contrast allergy, renal dysfunction)

Hypercoagulable Work-up

Indications: Idiopathic VTE or no overt risk factors, < 40 years old

Laboratory panel components: Antiphospholipid antibodies, Factor V Leiden, Protein C, Protein S, Antithrombin III