Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial

• Published in: Blood 2008-12, Vol.112 (12), p.4432-4436
• Main Authors: Kearon, Clive, Julian, Jim A., Kovacs, Michael J., Anderson, David R., Wells, Philip, MacKinnon, Betsy, Weitz, Jeffrey I., Crowther, Mark A., Dolan, Sean, Turpie, Alexander G., Geerts, William, Solymoss, Susan, van Nguyen, Paul, Demers, Christine, Kahn, Susan R., Kassis, Jeannine, Rodger, Marc, Hambleton, Julie, Gent, Michael, Ginsberg, Jeffrey S.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anticoagulants - administration & dosage; Anticoagulants - therapeutic use; Dose-Response Relationship, Drug; Double-Blind Method; Factor V - physiology; Female; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Recurrence; Risk Factors; Thrombophilia - complications; Thrombophilia - epidemiology; Thrombophilia - genetics; Treatment Outcome; Venous Thromboembolism - epidemiology; Venous Thromboembolism - etiology; Venous Thromboembolism - genetics; Warfarin - administration & dosage; Warfarin - therapeutic use
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2008-06-163279

We sought to determine whether thrombophilic defects increase recurrent venous thromboembolism (VTE) during warfarin therapy. Six hundred sixty-one patients with unprovoked VTE who were randomized to extended low-intensity (international normalized ratio [INR], 1.5-1.9) or conventional-intensity (INR, 2.0-3.0) anticoagulant therapy were tested for thrombophilia and followed for a mean of 2.3 years. One or more thrombophilic defects were present in 42% of patients. The overall rate of recurrent VTE was 0.9% per patient-year. Recurrent VTE was not increased in the presence of factor V Leiden (hazard ratio [HR], 0.7; 95% CI, 0.2-2.6); the 20210G>A prothrombin gene mutation (HR, 0); antithrombin deficiency (HR, 0); elevated factor VIII (HR, 0.7; 95% CI, 0.1-5.4); elevated factor XI (HR, 0.7; 95% CI, 0.1-5.0), or elevated homocysteine (HR, 0.7; 95% CI, 0.1-5.3), but showed a trend to an increase with an antiphospholipid antibody (HR, 2.9; 95% CI, 0.8-10.5). Compared with patients with no thrombophilic defects, the rate of recurrence was not increased in the presence of one (HR, 0.7; 95% CI, 0.2-2.3) or more than one (HR, 0.7; 95% CI, 0.2-3.4) defect. We conclude that single or multiple thrombophilic defects are not associated with a higher risk of recurrent VTE during warfarin therapy.