The risk of recurrent venous thromboembolism in heterozygous carriers of factor V Leiden and a first spontaneous venous thromboembolism.
BACKGROUND
Factor V (FV) Leiden is a risk factor for venous thrombosis (VT). Data on its influence on the risk of recurrent venous thromboembolism (VTE) are controversial owing to different study designs and patient cohorts.


METHODS
We reevaluated the risk of recurrence among heterozygous carriers and noncarriers of FV Leiden with a first spontaneous proximal VT of the leg and/or pulmonary embolism. Patients with secondary VTE, homozygous FV Leiden, natural inhibitor deficiencies, lupus anticoagulant, cancer, or long-term anticoagulation were excluded. The study end point was objectively documented, symptomatic, recurrent VTE.


RESULTS
After discontinuation of oral anticoagulant therapy for a first VTE, we prospectively observed 287 patients, 83 (29%) of whom were heterozygous for FV Leiden. Recurrent VTE was seen in 17 (20%) of 83 patients with and 44 (21.6%) of 204 without FV Leiden. The probability of recurrence among heterozygotes was 12% (95% confidence interval [CI], 8%-16%), 27% (95% CI, 21%-33%), and 27% (95% CI, 21%-33%) after 2, 4, and 6 years, respectively, and was not higher than that among patients without the mutation (16%, 23%, and 34%, respectively). The relative risk of recurrence in heterozygotes was 0.9 (95% CI, 0.5-1.6; P =.60) after adjustment for confounding variables. The risk of recurrence among patients with and without FV Leiden was not different when sex distribution or duration of anticoagulation therapy was taken into account.


CONCLUSIONS
The risk of recurrence is similar among carriers and noncarriers of FV Leiden. Heterozygous patients should receive secondary thromboprophylaxis for a similar length of time as patients without FV Leiden.
Eichinger
Sabine
S
Department of Internal Medicine I, Division of Hematology and Hemostasis, University of Vienna, Waehringer Guertel 18-20, 1090 Wien, Austria. sabine.eichinger@akh-wien.ac.at
Weltermann
Ansgar
A
Mannhalter
Christine
C
Minar
Erich
E
Bialonczyk
Christine
C
Hirschl
Mirko
M
Schönauer
Verena
V
Lechner
Klaus
K
Kyrle
Paul A
PA
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012008:Recurrence; D018570:Risk Assessment; D013923:Thromboembolism / Q000235:genetics*; D020246:Venous Thrombosis / Q000235:genetics*
C095381:factor V Leiden; D005165:Factor V