Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial.
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.
Kearon
Clive
C
McMaster University, Hamilton, ON. kearonc@mcmaster.ca
Julian
Jim A
JA
Kovacs
Michael J
MJ
Anderson
David R
DR
Wells
Philip
P
Mackinnon
Betsy
B
Weitz
Jeffrey I
JI
Crowther
Mark A
MA
Dolan
Sean
S
Turpie
Alexander G
AG
Geerts
William
W
Solymoss
Susan
S
van Nguyen
Paul
P
Demers
Christine
C
Kahn
Susan R
SR
Kassis
Jeannine
J
Rodger
Marc
M
Hambleton
Julie
J
Gent
Michael
M
Ginsberg
Jeffrey S
JS
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*
D000925:Anticoagulants; C095381:factor V Leiden; D014859:Warfarin; D005165:Factor V