What are the common causes and risk factors for deep vein thrombosis (DVT)?

Deep Vein Thrombosis: Causes and Risk Factors

Deep vein thrombosis results from the interaction of three fundamental pathophysiologic mechanisms—venous stasis, endothelial injury, and hypercoagulability (Virchow's triad)—with specific patient, disease, and treatment-related risk factors contributing to varying degrees of thrombotic risk. 1, 2, 3

Pathophysiologic Framework

The formation of DVT requires disruption of normal hemostatic balance through:

• Venous stasis from immobility, which produces endothelial activation and promotes platelet and leukocyte adhesion 3
• Vascular injury that triggers tissue factor expression and coagulation cascade activation 2, 3
• Hypercoagulability from inherited or acquired prothrombotic states that shift the balance toward clot formation 2, 4

These mechanisms work in concert, with neutrophil extracellular traps and inflammatory mediators amplifying thrombus formation and growth 3.

Strongest Individual Risk Factors

Prior DVT History

• Previous DVT is the single most powerful predictor, increasing odds 6-fold and accounting for 23% of total population risk 1
• This represents the highest individual contribution to thrombotic risk among all measurable factors 1

Inherited Thrombophilia

• Documented thrombophilic disorders increase DVT odds 5.9-fold, contributing 22% of overall risk 1
• Factor V Leiden is the most common inherited variant, affecting approximately 5% of Caucasians 1
• Prothrombin G20210A mutation also confers significant risk 1, 4
• Natural anticoagulant deficiencies (antithrombin III, protein C, protein S) carry an odds ratio of 11.1 5, 1
• Testing for thrombophilia should be reserved for young patients, unprovoked events, atypical clot locations, recurrent thrombosis, or strong family history 1

Immobility and Hospitalization

• Prolonged immobility elevates DVT odds 3.2-fold and represents 14.4% of total risk 1
• Acute paralysis (e.g., spinal cord injury) increases odds 3-fold, accounting for 13.6% of risk 1
• Hospital admission alone raises annual DVT incidence to 239 per 100,000 hospitalized patients 1
• Hospitalization contributes to more than 547,000 DVT cases annually in the United States 1

Malignancy-Associated Risk

• Active cancer increases DVT odds 2.65-fold, contributing 12.3% of total risk and accounting for 20% of community VTE cases 1
• Pancreatic cancer carries the highest risk among solid tumors, followed by brain, lung, ovarian, renal, and gastric malignancies 1, 6
• Hematologic malignancies—particularly high-grade lymphoma, acute leukemia, and multiple myeloma—confer especially elevated risk 6
• Metastatic disease amplifies risk dramatically, with distant metastases conferring an odds ratio of 19.8 compared to localized disease 1
• The first three months following cancer diagnosis represent the period of maximal thrombotic risk 1

Treatment-Related Factors

Chemotherapy and Cancer Therapies

• Active chemotherapy elevates DVT odds approximately 6.5-fold 1, 6
• Anti-angiogenic agents (thalidomide, lenalidomide, bevacizumab) substantially increase thrombotic risk 1, 6
• Erythropoiesis-stimulating agents are linked to elevated VTE risk 1, 6

Hormonal Therapies

• Oral contraceptives and hormone replacement therapy increase DVT incidence 1, 6
• Tamoxifen and raloxifene are associated with higher thrombotic risk 1, 6

Surgical and Traumatic Injury

• Recent major surgery (within 3 months) is a major transient risk factor 6
• In cancer patients, recent surgery doubles postoperative DVT risk and triples fatal PE risk 1
• Lower-extremity fractures significantly increase thrombotic risk, particularly in patients over 60 years 1
• Traumatic injury is a major predictor in validated post-traumatic risk scores 1

Medical Comorbidities

Critical Illness and Infection

• Critical illness requiring ICU/CCU care raises DVT risk 1.65- to 2.1-fold, contributing 6-14% of total risk 1, 6
• Acute infections increase DVT odds 1.48-fold (4.9% of risk) and are associated with a 3-fold rise in VTE incidence within three months 1

Chronic Conditions

• Renal insufficiency is an established independent risk factor 1
• Chronic inflammatory diseases (inflammatory bowel disease, rheumatoid arthritis) serve as persistent provoking factors 6
• Heart failure increases DVT risk 7
• Behçet's disease, particularly in Asian populations, is associated with increased risk 6

Patient Demographics

• Age over 60 years modestly raises DVT odds (OR 1.34), accounting for 3.6% of overall risk burden 1
• Obesity (BMI >30 kg/m²) is an established independent risk factor 1
• Male sex represents an intrinsic risk factor that affects individual recurrence risk 6

Laboratory and Clinical Markers

• Thrombocytosis (pre-chemotherapy platelet count ≥350 × 10⁹/L) is associated with increased thrombosis risk 1
• Leukocytosis is an established laboratory risk factor 1
• Elevated D-dimer and fibrinogen serve as biomarkers indicating heightened thrombotic risk 1
• Elevated C-reactive protein is probably associated with DVT (moderate certainty evidence) 1
• Clinical signs including tachycardia, fever, and peripheral leg edema correlate with higher thrombotic risk 1

Central Venous Catheters and Devices

• Indwelling venous devices (catheters, dialysis lines) are the highest risk factor for upper extremity DVT 7
• Central venous catheter placement in cancer patients is an additional recognized risk factor 1
• Risk increases with the number of catheter lumens 7
• Left-sided placements carry higher DVT incidence than right-sided placements 7

Clinical Considerations

Common pitfall: Multifactorial etiology is the rule rather than the exception—46% of patients have two or more prothrombotic factors, and 18% have three or more risk factors 6. Do not stop searching for risk factors after identifying one cause.

Important distinction: Intrinsic risk factors (hereditary thrombophilia, male sex, advanced age) do not change the classification of provoked versus unprovoked thrombosis but do affect individual recurrence risk and duration of anticoagulation decisions 6.