Is Smoking a Cause of Deep Vein Thrombosis?
Yes, smoking is a modest independent risk factor for DVT, increasing risk by approximately 23% in current smokers, though this effect is substantially weaker than other established DVT risk factors and appears partially mediated through smoking-related comorbidities. 1
Magnitude of Risk
Current smoking increases DVT risk with a relative risk of 1.23 (95% CI 1.14-1.33) compared to never smokers, based on meta-analysis of 32 observational studies involving nearly 4 million participants. 1 Former smokers have a lower but still elevated risk (RR 1.10,95% CI 1.03-1.17). 1
The risk demonstrates a dose-response relationship:
- Risk increases by 10.2% for every additional 10 cigarettes smoked per day 1
- Risk increases by 6.1% for every additional 10 pack-years of smoking 1
- Young current smokers with ≥20 pack-years show the highest relative risk (OR 4.30,95% CI 2.59-7.14) 2
Mechanism and Clinical Context
The relationship between smoking and DVT appears partially mediated through smoking-related comorbidities rather than purely direct thrombotic effects. 3 When adjusted for cardiovascular disease, heart failure, cancer, recent hospitalizations, and physical activity, the association is substantially attenuated. 3
Smoking-induced polycythemia contributes to thrombotic risk through increased blood viscosity caused by carbon monoxide exposure, which triggers compensatory erythropoiesis. 4 Carbon monoxide binds hemoglobin with 200-250 times greater affinity than oxygen, creating a hypoxic state that increases red blood cell production. 4
Synergistic Effects
Smoking acts synergistically with other risk factors, particularly in young women:
- Women who smoke and use oral contraceptives have an 8.8-fold increased risk (OR 8.79,95% CI 5.73-13.49) compared to non-smoking women not using contraceptives 2
- Smoking combined with Factor V Leiden mutation yields a 5.0-fold increased risk 2
- Smoking with prothrombin 20210A mutation yields a 6.0-fold increased risk 2
Comparison to Established Risk Factors
Smoking's effect is substantially weaker than established DVT risk factors:
- History of prior VTE: OR 6.08 5, 6
- Thrombophilia: OR 5.88 5
- Active malignancy: OR 2.65 5, 6
- Immobility (>72 hours): OR 3.17 5, 6
- Critical illness: OR 1.65 5, 6
Daily smoking before pregnancy increases post-thrombotic syndrome risk (OR 2.9,95% CI 1.3-6.4) in women with pregnancy-associated DVT. 5
Population Impact
Smoking accounts for 5.8% of all VTE cases (population attributable fraction), translating to an absolute risk increase of 24.3 cases per 100,000 person-years. 1
Clinical Implications
Body mass index appears to be a confounding factor in risk estimates—studies adjusted for BMI show relatively higher risk (RR 1.30,95% CI 1.24-1.37) for current smokers. 1
Smoking cessation reduces thrombotic risk, with risk reduction beginning within 1 year and returning to baseline after 5 years. 4 This parallels the well-established stroke risk reduction pattern with smoking cessation. 7
Important Caveat
One older study from 1978 paradoxically found smoking associated with reduced DVT incidence, though this achieved only marginal statistical significance (p=0.10) and conflicts with all modern evidence. 8 This outlier should not influence clinical decision-making given the overwhelming contemporary evidence demonstrating increased risk.
Clinical Recommendations
Smoking cessation should be strongly recommended as part of VTE risk reduction strategies, particularly in patients with multiple risk factors or those requiring oral contraceptives. 1, 2 While smoking's independent effect is modest, its synergistic effects with other risk factors and contribution to overall cardiovascular morbidity make cessation clinically important. 2, 3