Pathophysiology of Venous Thrombosis
Venous thrombosis develops through three fundamental mechanisms known as Virchow's triad: blood stasis, hypercoagulability, and endothelial injury or dysfunction. 1
Core Pathophysiologic Mechanisms
Blood Stasis
- Reduced or turbulent blood flow allows prolonged contact between coagulation factors and the vessel wall, creating the foundation for thrombus formation. 1
- Stasis occurs during immobilization (general anesthesia, stroke with hemiparesis), heart failure, and post-surgical states. 1, 2
- Venous thrombosis forms specifically in areas of slow flow where coagulation activation becomes the critical mechanism. 3
Hypercoagulability
- Inherited thrombophilias include protein C deficiency, protein S deficiency, antithrombin III deficiency, Factor V Leiden, and prothrombin G20210A mutation. 1
- Acquired hypercoagulable states encompass malignancy, pregnancy/postpartum, oral contraceptives, inflammatory conditions, and elevated fibrinogen levels. 1
- In cancer patients, hypercoagulability results from procoagulants such as tissue factor expressed by cancer cells. 4, 5
Endothelial Injury or Dysfunction
- Central line placement, surgical trauma, and inflammatory conditions cause direct vascular injury that initiates thrombosis. 1
- Endothelial dysfunction is evidenced by elevated von Willebrand factor levels in conditions like atrial fibrillation. 1
- Vessel wall injury from stasis and hypoxia releases thromboplastin and exposes collagen, triggering the thrombotic cascade. 2
Thrombus Composition and Structure
Venous thrombi are predominantly composed of red blood cells with large amounts of interspersed fibrin and relatively few platelets, distinguishing them fundamentally from arterial thrombi. 4, 3
- Venous thrombi form under conditions of stasis rather than high flow. 4
- As thrombi age, leukocytes become incorporated through chemotactic factors released from aggregated platelets. 4
- Aggregated platelets eventually swell, disintegrate, and are gradually replaced by fibrin. 4
- The fibrin clot is ultimately digested by fibrinolytic enzymes released from endothelial cells and leukocytes. 4
Clinical Consequences
- Venous thrombosis causes complications through local vessel obstruction, distant embolism (particularly pulmonary embolism), or consumption of hemostatic elements. 4
- Pulmonary embolism from venous thrombosis is a leading cause of death, with approximately 60,000-100,000 deaths annually in the United States. 6
- In cancer patients, VTE increases mortality risk by 2- to 6-fold. 4, 5
Special Considerations
Cancer-Associated Thrombosis
- Pathophysiology includes vessel wall damage and vessel stasis from direct tumor compression in addition to hypercoagulability. 4, 5
- Additional risk factors include chemotherapeutic regimens, surgical procedures, and prolonged immobilization. 5
Mesenteric Venous Thrombosis
- Approximately 20% of cases are idiopathic despite known risk factors. 4
- Bowel edema and increased vascular resistance secondary to venous thrombosis reduce arterial blood flow, leading to bowel ischemia. 4
Treatment Implications
Anticoagulants are highly effective for prevention and treatment of venous thromboembolism because coagulation activation is the critical pathophysiologic mechanism. 3