What are the main risk factors for Deep Vein Thrombosis (DVT), including provoked and unprovoked factors?

Risk Factors for Deep Vein Thrombosis

DVT risk factors are categorized into provoked (transient or persistent) and unprovoked based on their association with recurrence risk and duration of anticoagulation needed, with the classification directly impacting treatment duration and patient outcomes. 1

Provoked vs. Unprovoked DVT: Core Distinction

Unprovoked DVT occurs without any identifiable environmental risk factors and carries an intermediate recurrence risk (>5% annually), while provoked DVT occurs in the presence of specific triggers that can be transient or persistent. 1, 2

Key Clinical Implication

• The single most important variable influencing recurrent VTE risk after stopping anticoagulation is whether an environmental provoking factor was present. 1
• Provoked DVT with major transient factors: <1% annual recurrence risk 2
• Unprovoked DVT: >5% annual recurrence risk 2
• Persistent risk factors: highest recurrence risk 1, 2

Major Transient Risk Factors (Within 3 Months Before DVT)

These factors confer a >10-fold increase in first VTE risk or reduce recurrence risk by half when present: 1

• Surgery with general anesthesia >30 minutes 1
• Hospital bed confinement ≥3 days (bathroom privileges only) with acute illness 1
• Cesarean section 1

Mechanism: Surgery and Trauma

Surgery and trauma increase DVT risk through multiple pathways: endothelial damage from tissue injury, venous stasis from immobilization, and activation of the coagulation cascade from the inflammatory response. 3 Major surgery triggers a hypercoagulable state that persists for up to 3 months. 1

Minor Transient Risk Factors (Within 2 Months Before DVT)

These factors confer a 3-10-fold increase in first VTE risk: 1

• Surgery with general anesthesia <30 minutes 1
• Hospital admission <3 days with acute illness 1
• Estrogen therapy (oral contraceptives, hormone replacement) 1
• Pregnancy or puerperium 1
• Bed confinement outside hospital ≥3 days with acute illness 1
• Leg injury with reduced mobility ≥3 days 1

Mechanism: Immobility

Immobilization causes venous stasis by reducing the muscle pump action in the lower extremities, leading to blood pooling and activation of clotting factors. 3 The duration threshold of ≥3 days reflects the time needed for significant endothelial changes and thrombus formation. 1

Oral Contraceptives and Pregnancy Contribution

Estrogen-containing contraceptives and pregnancy increase DVT risk through multiple mechanisms: increased hepatic synthesis of clotting factors (especially factors VII, VIII, X), decreased natural anticoagulants (protein S), and venous stasis (particularly in pregnancy due to uterine compression of pelvic veins). 1 These are classified as minor transient factors requiring occurrence within 2 months of DVT to be considered provoked. 1

Persistent Risk Factors

Active cancer is the most important persistent risk factor: 1

• Cancer not receiving potentially curative treatment 1
• Evidence of recurrent or progressive disease 1
• Ongoing cancer treatment 1

Other persistent factors: 1

• Inflammatory bowel disease (≥2-fold recurrence risk) 1
• Chronic inflammatory conditions 4
• Autoimmune diseases 4

Malignancy Mechanism

Cancer increases thrombosis risk through tumor-secreted procoagulants (tissue factor, cancer procoagulant), inflammatory cytokines, direct vascular invasion, and treatment-related factors (chemotherapy, central lines). 3 Cancer-associated VTE requires indefinite anticoagulation due to persistent high recurrence risk. 2, 5

Inherited Thrombophilias (Non-Environmental Risk Factors)

Critical distinction: Hereditary thrombophilias do NOT classify DVT as "provoked" but may influence recurrence risk. 1

Common Inherited Thrombophilias:

• Factor V Leiden (most common hereditary thrombophilia) 3
• Prothrombin G20210A mutation 3
• Protein C deficiency 3
• Protein S deficiency 3
• Antithrombin deficiency (highest thrombotic risk) 3

Clinical Caveat

The presence of hereditary thrombophilia in a patient with DVT does NOT change the classification from "unprovoked" to "provoked" because these are intrinsic, not environmental, factors. 1 However, they may influence decisions about anticoagulation duration. 5

Additional Risk Factors Affecting Classification

Factors that increase first VTE risk but don't necessarily classify as provoked: 1

• Older age 1
• Male sex 1, 5
• Obesity 3
• Prior VTE history 3

Clinical Algorithm for Risk Factor Assessment

Step 1: Identify if major transient risk factor occurred within 3 months of DVT 1

• If yes → Provoked by major transient factor → 3 months anticoagulation typically sufficient 2, 5

Step 2: If no major factor, assess for minor transient risk factor within 2 months 1

• If yes → Provoked by minor transient factor → 3 months anticoagulation typically sufficient 2, 5

Step 3: If no transient factors, assess for persistent risk factors 1

• Active cancer or ongoing inflammatory condition → Provoked by persistent factor → Indefinite anticoagulation 2, 5

Step 4: If no transient or persistent factors identified 1

• Classify as unprovoked → Consider extended or indefinite anticoagulation 2, 5

Important Clinical Pitfalls

Timing is critical: A major risk factor that occurred >3 months before DVT does NOT qualify the event as provoked. 1 Similarly, minor factors must occur within 2 months. 1

Weak risk factors: Minor soft tissue leg injury without ≥3 days reduced mobility does NOT qualify as a provoking factor. 1

Cancer status: Cancer is only considered "active" if meeting specific criteria; a patient in long-term remission after curative treatment does NOT have a persistent risk factor. 1

Hormone therapy: Must have occurred within 2 months of DVT to be considered provoked; if discontinued, recurrence risk is lower. 2