What are the causes of arterial and venous thrombosis?

Causes of Arterial and Venous Thrombosis

Arterial and venous thrombosis arise from fundamentally different pathophysiological mechanisms, though they share several common risk factors. 1

Arterial Thrombosis

Primary Mechanism

Arterial thrombi form under high-flow conditions at sites of atherosclerotic plaque rupture, where exposed subendothelium triggers platelet aggregation and coagulation activation. 1 The thrombi are predominantly composed of platelet aggregates bound by thin fibrin strands, reflecting the high-shear environment in which they develop. 1

Key Causes

• Atherosclerotic plaque rupture exposing thrombogenic subendothelium to platelets and coagulation proteins 1
• Plaque hemorrhage causing further vessel narrowing and flow disturbance 1
• Disturbed blood flow in regions of severe stenosis or slow flow 1
• Endothelial dysfunction with elevated von Willebrand factor levels, particularly in atrial fibrillation 2

Clinical Context

Arterial thrombi typically occur in association with preexisting atherosclerotic vascular disease and produce tissue ischemia through vessel obstruction or distal embolization. 1 Both platelet activation and coagulation cascade activation are critical, making both antiplatelet agents and anticoagulants potentially effective. 1

Venous Thrombosis

Primary Mechanism

Venous thrombi form in areas of stasis under low-flow conditions and are predominantly composed of red blood cells with abundant fibrin and relatively few platelets. 1, 2 Activation of blood coagulation is the critical pathogenic mechanism, while platelet activation plays a lesser role. 1

Virchow's Triad Components

Stasis of Blood Flow 2, 3

• Immobilization during general anesthesia or prolonged bed rest 2, 3
• Stroke with hemiparesis 2
• Heart failure 2, 3
• Atrial fibrillation 2
• Venous insufficiency 2
• Post-surgical states 2

Endothelial Injury or Dysfunction 2

• Central line placement 2
• Surgical trauma 2
• Inflammatory conditions 2, 3
• Vessel wall injury from stasis and hypoxia 3

Hypercoagulability 2, 4

Inherited thrombophilias:

• Factor V Leiden mutation 1, 4
• Prothrombin G20210A mutation 1, 4
• Protein C deficiency 1, 4
• Protein S deficiency 1, 4
• Antithrombin III deficiency 1, 4

Acquired hypercoagulable states:

• Malignancy with tumor-expressed tissue factor 2
• Pregnancy and postpartum period (6 weeks after delivery carries highest risk) 1, 2
• Oral contraceptives 1, 2
• Inflammatory conditions 2
• Elevated fibrinogen levels 2
• Antiphospholipid antibody syndrome 1

Specific Venous Thrombosis Contexts

Cerebral Venous Sinus Thrombosis 2

• Hypercoagulable states (most common predisposing factor) 1
• Pregnancy 1
• Malignancy 1
• Hyperhomocysteinemia 1

Mesenteric Venous Thrombosis 1, 2

• Inflammatory processes (acute pancreatitis, inflammatory bowel disease) 1
• Surgical trauma (splenectomy, bariatric surgery) 1
• Idiopathic in 20-36% of cases 1, 2
• Inherited thrombophilias 1
• Malignancies and hematologic disorders 1

Splanchnic Vein Thrombosis (Budd-Chiari, Portal Vein) 1

• Myeloproliferative neoplasms (49% in Budd-Chiari, 21% in portal vein thrombosis) 1
• JAK2 mutation positive disease 1
• Paroxysmal nocturnal hemoglobinuria (9-19% of Budd-Chiari cases) 1
• Hormonal factors including oral contraceptives (33-44%) 1

Shared Risk Factors and Interrelationship

Recent evidence challenges the traditional view of arterial and venous thrombosis as completely separate entities. 5, 6, 7, 8 Common risk factors include:

• Age (exponential increase in risk, particularly after 75 years) 1, 5, 6, 7, 8
• Obesity 5, 6, 7, 8
• Metabolic syndrome 5, 6, 7, 8
• Diabetes mellitus 6, 7, 8
• Hypertension 6, 7, 8
• Hypertriglyceridemia 6, 7, 8
• Smoking 7
• Infections 6, 7, 8
• Malignancies 6, 7, 8

Common Pathophysiological Link

Inflammation represents a fundamental mechanism triggering thrombus formation in both arterial and venous systems. 5 During inflammation, procoagulant factor production increases, anticoagulant mechanisms are down-regulated, and endogenous fibrinolytic activity is inhibited. 5 Patients with venous thromboembolism demonstrate increased risk of subsequent arterial events and vice versa. 5, 6, 7, 8

Special Populations

Pediatric Considerations 1

• Prothrombotic abnormalities identified in 20-50% of children with acute ischemic stroke 1
• Factor V Leiden mutation shows 4.3-fold increased incidence in pediatric stroke 1
• Homocystinuria causes both arterial and venous occlusion with rapidly progressive arteriosclerotic disease 1

Hematologic Disorders 1

• Hemolytic-uremic syndrome 1
• Thrombotic thrombocytopenic purpura 1
• Polycythemia rubra vera 1
• Essential thrombocythemia 1
• Disseminated intravascular coagulation 1

Clinical Pitfalls

• Normal CT does not exclude cerebral venous sinus thrombosis; proceed to CTV or MRV when clinical suspicion remains high 2
• Thrombocytosis and erythrocytosis may be masked in splanchnic vein thrombosis due to portal hypertension and hypersplenism 1
• Isolated headache without focal findings occurs in 25% of cerebral venous sinus thrombosis cases 2
• Median 7-day delay from symptom onset to cerebral venous sinus thrombosis diagnosis is common 2