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Previous Volume 336:399-403 February 6, 1997 Number 6 Next

The Risk of Recurrent Venous Thromboembolism in Patients with an Arg⁵⁰⁶Gln Mutation in the Gene for Factor V (Factor V Leiden)

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ABSTRACT

Background A recently discovered mutation in coagulation factor V (Arg⁵⁰⁶Gln, referred to as factor V Leiden), which results in resistance to activated protein C, is found in approximately one fifth of patients with venous thromboembolism. However, the risk of recurrent thromboembolism in heterozygous carriers of this genetic abnormality is unknown.

Methods We searched for factor V Leiden in 251 unselected patients with a first episode of symptomatic deep-vein thrombosis diagnosed by venography. The patients were followed prospectively for a mean of 3.9 years to determine the frequency of recurrent venous thrombosis and pulmonary embolism.

Results Factor V Leiden was found in 41 of the patients (16.3 percent; 95 percent confidence interval, 11.8 to 20.9 percent). The cumulative incidence of recurrent venous thromboembolism after follow-up of up to eight years was 39.7 percent (95 percent confidence interval, 22.8 to 56.5 percent) among carriers of the mutation, as compared with 18.3 percent (95 percent confidence interval, 12.3 to 24.3 percent) among patients without the mutation (hazard ratio, 2.4; 95 percent confidence interval, 1.3 to 4.5; P<0.01).

Conclusions The risk of recurrent thromboembolic events is significantly higher in carriers of factor V Leiden than in patients without this abnormality. Large trials assessing the risk–benefit ratio of long-term anticoagulation in carriers of the mutation who have had a first episode of venous thromboembolism are indicated.

Source Information

From the Institute of Medical Semiotics, University Hospital of Padua, Padua, Italy (P.S., P.P., A.S., C.S., S.V., F.D., A.G.); and the Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research (A.W.A.L.) and the Department of Clinical Epidemiology (M.H.P.), Academic Medical Center, University of Amsterdam, Amsterdam.

Address reprint requests to Dr. Lensing at the Center for Hemostasis, Thrombosis, Atherosclerosis, and Inflammation Research, Academic Medical Center F4-237, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.

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