FACTOR-V LEIDEN AND RISKS OF RECURRENT IDIOPATHIC VENOUS THROMBOEMBOLISM

Background Whether Leiden mutation in the gene coding for coagulation factor V is associated with recurrent idiopathic venous thromboembolis m (VTE) is unknown, but such data are necessary to evaluate the merits of genetic screening in secondary prevention of thromboembolic diseas e. Methods and Results Among 14 916 apparently healthy men who provide d DNA samples and were followed in the Physicians' Health Study throug h August 1994, 77 suffered an idiopathic VTE. These 77 men were follow ed for an additional average period of 68.3 months, during which time. 11 (14.3%) suffered a recurrent idiopathic VTE. Factor V Leiden status was assessed in these men,and incidence rates of recurrence were calc ulated by genotype. All recurrent events occurred after cessation of a nticoagulation. Seven recurrences occurred among 63 genetically unaffe cted subjects (11.1%; incidence rate, 1.82 per 100 person-years), whil e four occurred among those 14 heterozygous for factor V Leiden (28.6% ; incidence rate. 7.46 per 100 person-years). Thus, factor V Leiden wa s associated with a fourfold to fivefold increase in risk of recurrent VTE (crude relative risk 4.1; P=.041 age- and smoking-adjusted relati ve risk, 4.7; P=.047). There was no difference in mean time between in dex and recurrent events by genotype. Among heterozygous men, 76% of r ecurrent events were attributable to mutation. Conclusions In prospect ive evaluation of 77 men with a history of idiopathic VTE. factor V Le iden was associated with a fourfold to fivefold increased risk of recu rrent thrombosis. These data raise the possibility that patients with VTE affected by factor V Leiden may require more prolonged anticoagula tion to prevent recurrent disease compared with those without mutation .