title: Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial.
abstract: 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.
authors.affiliation: McMaster University, Hamilton, ON. kearonc@mcmaster.ca
authors.forename: Clive
authors.initials: C
authors.lastname: Kearon
authors.forename: Jim A
authors.initials: JA
authors.lastname: Julian
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kovacs
authors.forename: David R
authors.initials: DR
authors.lastname: Anderson
authors.forename: Philip
authors.initials: P
authors.lastname: Wells
authors.forename: Betsy
authors.initials: B
authors.lastname: Mackinnon
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Weitz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Crowther
authors.forename: Sean
authors.initials: S
authors.lastname: Dolan
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Turpie
authors.forename: William
authors.initials: W
authors.lastname: Geerts
authors.forename: Susan
authors.initials: S
authors.lastname: Solymoss
authors.forename: Paul
authors.initials: P
authors.lastname: van Nguyen
authors.forename: Christine
authors.initials: C
authors.lastname: Demers
authors.forename: Susan R
authors.initials: SR
authors.lastname: Kahn
authors.forename: Jeannine
authors.initials: J
authors.lastname: Kassis
authors.forename: Marc
authors.initials: M
authors.lastname: Rodger
authors.forename: Julie
authors.initials: J
authors.lastname: Hambleton
authors.forename: Michael
authors.initials: M
authors.lastname: Gent
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Ginsberg
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005165:Factor V / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; C095381:factor V Leiden; D014859:Warfarin; D005165:Factor V