What are the main risk factors for Deep Vein Thrombosis (DVT)?

Risk Factors for Deep Vein Thrombosis (DVT)

Provoked vs. Unprovoked DVT

DVT is classified as provoked when precipitated by identifiable transient or persistent risk factors, while unprovoked DVT occurs without any identifiable trigger—this distinction is critical because unprovoked DVT carries a 30% recurrence risk at 5 years compared to only 3% for surgery-provoked DVT. 1

Provoked DVT Categories:

Transient Risk Factors (resolve within 2 weeks):

• Major surgery (strongest transient risk factor) 1
• Major trauma or fractures 1, 2
• Hospitalization with acute medical illness 1
• Pregnancy and postpartum period (up to 6 weeks) 1

Persistent/Chronic Risk Factors:

• Active malignancy (48.7% of continuous risk DVT cases) 1, 2
• Inflammatory bowel disease and autoimmune disorders 1
• Inherited thrombophilias 1, 2
• Chronic immobilization 2

Immobility, Surgery, and Trauma

Surgery increases DVT risk through a combination of endothelial injury, venous stasis, and activation of coagulation cascades, with risk varying by procedure type: 5% for herniorrhaphy, 15-30% for major abdominal surgery, and 50-75% for hip fracture surgery. 1

Mechanisms of increased risk:

• Immobilization produces venous stasis leading to endothelial activation, which promotes platelet and leukocyte adhesion 3
• Even short-term immobilization (one week) significantly increases VTE risk 1
• Spinal cord injuries carry 50-100% DVT risk without prophylaxis 1
• Trauma and fractures cause direct endothelial damage and trigger inflammatory responses that activate coagulation 1, 3

Inherited Thrombophilias

Factor V Leiden is the most common inherited thrombophilia, present in 5.1% of non-Hispanic whites and found in 15-20% of patients with initial VTE, increasing risk 4-7 fold for heterozygotes. 1

Key inherited thrombophilias:

• Factor V Leiden (R506Q mutation): Most prevalent; heterozygosity increases VTE risk 4-7 fold, homozygosity increases risk substantially more 1
• Prothrombin G20210A mutation: Second most common genetic risk factor 1
• Antithrombin deficiency: Natural anticoagulant deficiency 1
• Protein C deficiency: Impairs anticoagulant pathway 1
• Protein S deficiency: Cofactor for activated Protein C 1

Important caveat: Inherited thrombophilias typically act synergistically with acquired risk factors—up to half of genetically predisposed patients have multiple thrombophilic factors present at the time of VTE 1

Pregnancy, Malignancy, and Oral Contraceptives

Oral contraceptives, pregnancy, and malignancy all increase DVT risk through hypercoagulability, with estrogen-containing contraceptives and hormone replacement therapy being well-established acquired risk factors. 1

Pregnancy-Related Risk:

• Pregnancy itself is an unmodifiable risk factor due to physiologic hypercoagulability 1
• Postpartum DVT (especially proximal thrombosis) carries 6.3-fold increased odds of developing postthrombotic syndrome 1
• Age >33 years at index pregnancy increases PTS risk (OR 3.9) 1
• Daily smoking during pregnancy increases PTS risk (OR 2.9) 1

Malignancy:

• Cancer increases VTE risk 4-7 fold and is present in 48.7% of patients with continuous risk provoked DVT 1, 2
• Cancer-associated VTE has a 15% annualized recurrence risk 1
• Chemotherapy further increases thrombotic risk 1
• Prechemotherapy thrombocytosis and leukocytosis predict VTE in cancer patients 1

Hormonal Factors:

• Oral contraceptives (pills, patches, rings) increase VTE risk through estrogen-mediated hypercoagulability 1
• Estrogen replacement therapy similarly increases risk 1
• These factors act synergistically with inherited thrombophilias 1

Additional High-Risk Factors

Central venous catheters and indwelling devices represent the highest risk for upper extremity DVT, accounting for the majority of secondary UEDVT cases. 1

Other significant risk factors:

• Advanced age: VTE incidence increases with age, with most cases occurring between 60-70 years 1
• Obesity: Elevated BMI increases PTS risk up to 2-fold and is an independent VTE risk factor 1
• Prior VTE history: Independent risk factor for recurrent events (20% recurrence at 5 years, 30% at 10 years) 1
• Infection: Increases VTE risk 3-fold within 3 months of infectious event 1
• Heart failure and myocardial infarction: 5-35% DVT rate in acute MI patients 1
• Stroke with paralysis: 30-60% DVT rate in paralyzed leg 1

Critical clinical pearl: In most VTE patients, including up to half of those genetically predisposed, a combination of thrombophilic risk factors acts synergistically rather than in isolation 1

1, 4, 2, 3, 5, 6