A prospective study of asymptomatic carriers of the factor V Leiden mutation to determine the incidence of venous thromboembolism

Background: The factor V Leiden mutation is a common genetic defect associa ted with an increased risk for venous thromboembolism. The clinical implica tions for asymptomatic carriers of this mutation and, consequently, the use fulness of screening families in which a proband has both the mutation and venous thrombo embolism are unclear. Objective: To determine the incidence of venous thromboembolism in asymptom atic carriers of the factor V Leiden mutation. Design: Prospective cohort study. Setting: University hospitals in the Netherlands. Participants: 470 asymptomatic carriers of the factor V Leiden mutation (23 4 men, 236 women; mean age, 43 years [range, 15 to 88 years]), 12 of whom w ere homozygous. Carriers were identified by screening the first-degree rela tives (>15 years of age) of 247 symptomatic probands. Measurements: Objectively diagnosed episodes of venous thromboembolism and the relationship between incidence and exposure to high-risk situations. Results: Nine venous thromboembolic events were observed in 1564 observatio n-years, resulting in an annual incidence of 0.58% (95% CI, 0.26% to 1.10%) . The incidence of spontaneous venous thromboembolism was 0.26% (CI, 0.07% to 0.65%) per year; 3.5% (CI, 0.1% to 17.8%) per episode of surgery, trauma , or immobilization; 0.0% (CI, 0.0% to 19.5%) per pregnancy; 1.8% (CI, 0.4% to 5.2%) per year of oral contraceptive use; and 2.9% (CI, 0.8% to 15.3%) per year of use of hormone replacement therapy. Conclusions: The absolute annual incidence of spontaneous venous thromboemb olism in asymptomatic carriers of the factor V Leiden mutation is low and d oes not justify routine screening of the families of symptomatic patients.