High plasma levels of factor VIII and the risk of recurrent venous thromboembolism.

Background: A high plasma level of factor VIII is a risk factor for venous thromboembolism. We evaluated the risk of a recurrence of thrombosis after an initial episode of spontaneous venous thromboembolism among patients wit h high plasma levels of factor VIII. Methods: We studied 360 patients for an average follow-up period of 30 mont hs after a first episode of venous thromboembolism and discontinuation of o ral anticoagulants. Patients who had recurrent or secondary venous thromboe mbolism, a congenital deficiency of an anticoagulant, the lupus anticoagula nt, hyperhomocysteinemia, cancer, or a requirement for long-term treatment with antithrombotic drugs or who were pregnant were excluded. The end point was objectively documented, symptomatic recurrent venous thromboembolism. Results: Recurrent venous thromboembolism developed in 38 of the 360 patien ts (10.6 percent). Patients with recurrence had higher mean (+/-SD) plasma levels of factor VIII than those without recurrence (182+/-66 vs. 157+/-54 IU per deciliter, P=0.009). The relative risk of recurrent venous thrombosi s was 1.08 (95 percent confidence interval, 1.04 to 1.12; P<0.001) for each increase of 10 IU per deciliter in the plasma level of factor VIII. Among patients with a factor VIII level above the 90th percentile of the values i n the study population, the likelihood of recurrence at two years was 37 pe rcent, as compared with a 5 percent likelihood among patients with lower le vels (P<0.001). Among patients with plasma factor VIII levels above the 90t h percentile, as compared with those with lower levels, the overall relativ e risk of recurrence was 6.7 (95 percent confidence interval, 3.0 to 14.8) after adjustment for age, sex, the presence or absence of factor V Leiden o r the G20210A prothrombin mutation, and the duration of oral anticoagulatio n. Conclusions: Patients with a high plasma level of factor VIII have an incre ased risk of recurrent venous thromboembolism. (N Engl J Med 2000;343:457-6 2.) (C)2000, Massachusetts Medical Society.