(Circulation. 1995;92:2800-2802.)
© 1995 American Heart Association, Inc.
Articles |
Factor V Leiden and Risks of Recurrent Idiopathic Venous Thromboembolism
From the Divisions of Preventive Medicine (P.M.R., C.H.H.) and Cardiovascular Disease (P.M.R., S.Z.G., K.L.) and the Channing Laboratory (M.J.S.), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; the Department of Ambulatory Care and Prevention (C.H.H.), Harvard Medical School; and the Departments of Nutrition (M.J.S.) and Epidemiology (M.J.S., C.H.H.), Harvard School of Public Health, Boston, Mass; and the Division of Laboratory Medicine (J.P.M.), Washington University School of Medicine, St Louis, Mo.
Background Whether Leiden mutation in the gene coding for coagulation factor V is associated with recurrent idiopathic venous thromboembolism (VTE) is unknown, but such data are necessary to evaluate the merits of genetic screening in secondary prevention of thromboembolic disease.
Methods and Results Among 14 916 apparently healthy men who provided DNA samples and were followed in the Physicians' Health Study through August 1994, 77 suffered an idiopathic VTE. These 77 men were followed 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 calculated by genotype. All recurrent events occurred after cessation of anticoagulation. Seven recurrences occurred among 63 genetically unaffected subjects (11.1%; incidence rate, 1.82 per 100 person-years), while four occurred among those 14 heterozygous for factor V Leiden (28.6%; incidence rate, 7.46 per 100 person-years). Thus, factor V Leiden was associated with a fourfold to fivefold increase in risk of recurrent VTE (crude relative risk, 4.1; P=.04; age- and smoking-adjusted relative risk, 4.7; P=.047). There was no difference in mean time between index and recurrent events by genotype. Among heterozygous men, 76% of recurrent events were attributable to mutation.
Conclusions In prospective evaluation of 77 men with a history of idiopathic VTE, factor V Leiden was associated with a fourfold to fivefold increased risk of recurrent thrombosis. These data raise the possibility that patients with VTE affected by factor V Leiden may require more prolonged anticoagulation to prevent recurrent disease compared with those without mutation.
Key Words: coagulation • genes • embolism
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