What are the causes of arterial and venous thrombosis?

Causes of Arterial and Venous Thrombosis

Both arterial and venous thrombosis share common risk factors but also have distinct pathophysiological mechanisms, with arterial thrombosis typically occurring under high-flow conditions with platelet-rich thrombi and venous thrombosis developing in areas of stasis with red blood cell and fibrin-rich clots 1.

Common Pathophysiology: Virchow's Triad

The fundamental mechanisms of thrombosis are classically described by Virchow's triad:

1. Stasis of blood flow
2. Changes in the vessel wall (endothelial damage)
3. Changes in blood composition (hypercoagulability)

Arterial Thrombosis Causes

Primary Mechanisms

• Forms under high-flow conditions
• Primarily composed of platelet aggregates bound by thin fibrin strands 1
• Often associated with atherosclerotic plaque rupture

Risk Factors

• Atherosclerosis - primary underlying cause
• Hypertension
• Diabetes mellitus
• Smoking
• Hyperlipidemia
• Obesity
• Metabolic syndrome
• Advanced age

Specific Conditions

• Myeloproliferative neoplasms - particularly polycythemia vera and essential thrombocythemia 2
• Antiphospholipid syndrome - associated with recurrent arterial thrombosis 2
• Homocystinuria/hyperhomocysteinemia - causes progressive arteriosclerotic vascular disease 2
• Pregnancy and postpartum state - especially during the 6 weeks after delivery 2

Venous Thrombosis Causes

Primary Mechanisms

• Forms in areas of stasis
• Predominantly composed of red blood cells with large amounts of fibrin and fewer platelets 1
• Often begins in valve pockets of deep veins

Risk Factors

• Immobility/stasis - prolonged bed rest, long travel
• Surgery - especially orthopedic procedures
• Trauma
• Obesity
• Advanced age
• Pregnancy and postpartum state
• Hormonal contraceptives

Inherited Thrombophilias

• Factor V Leiden mutation - most common genetic cause, 4-11 fold increased risk of venous thrombosis 2
• Prothrombin G20210A mutation - second most common genetic cause, 4-5 fold increased risk 2
• Protein C deficiency - 11.1-fold increased risk 2
• Protein S deficiency - 16.2-fold increased risk 2
• Antithrombin III deficiency - 18.4-fold increased risk 2

Acquired Thrombophilias

• Antiphospholipid syndrome - present in 5-15% of venous thrombosis cases 2
• Malignancy - through multiple mechanisms including hypercoagulability
• Heparin-induced thrombocytopenia
• Paroxysmal nocturnal hemoglobinuria - especially associated with unusual site thrombosis like Budd-Chiari syndrome 2

Conditions Associated with Both Arterial and Venous Thrombosis

1. Antiphospholipid syndrome - causes both arterial and venous thrombosis through multiple mechanisms 2, 3
2. Hyperhomocysteinemia - independent risk factor for both arterial and venous thrombosis 2, 3
3. Myeloproliferative neoplasms - particularly polycythemia vera and essential thrombocythemia 2
4. Pregnancy and postpartum state - risk for both types of thrombosis 2
5. Inflammatory conditions - chronic inflammation creates prothrombotic state 4
6. Metabolic syndrome - affects both arterial and venous systems 3, 5

Emerging Concepts

Recent evidence suggests that arterial and venous thrombosis, traditionally viewed as distinct entities, may be more interconnected than previously thought:

• Patients with venous thromboembolism have higher risk of subsequent arterial thrombotic events 6, 7, 3
• Common inflammatory pathways may activate coagulation in both arterial and venous systems 4, 3
• Traditional cardiovascular risk factors (hypertension, diabetes, obesity) also increase venous thrombosis risk 3, 5

Clinical Implications

• Patients with unprovoked venous thromboembolism should be evaluated for underlying thrombophilias, especially when:

  • Thrombosis occurs at young age (<50 years)
  • Thrombosis occurs at unusual sites
  • There is a family history of thrombosis
  • Recurrent thrombotic events occur

• After treatment of venous thromboembolism, assessment for arterial thrombosis risk factors may be warranted 6

• Specific site thrombosis may have unique risk factor profiles:

  • Cerebral venous thrombosis is strongly associated with pregnancy, oral contraceptives, and thrombophilias 2
  • Mesenteric venous thrombosis is associated with local inflammatory conditions (pancreatitis, inflammatory bowel disease) and hypercoagulable states 2