High factor VIII and the risk of venous thromboembolism.

There is now convincing evidence that a high level of coagulation factor VIII is an important risk factor for venous thromboembolism. A factor VIII plasma concentration above 1500 IU/l is associated with an almost 5-fold risk for a first episode of venous thrombosis. In thrombosis patients high factor VIII has been shown to persist over time and is not related to an acute phase reaction. High factor VIII is also an important risk factor for recurrence of venous thrombosis. In a prospective cohort study factor VIII levels exceeding the 90th percentile of the patient population conferred an almost 7-fold risk of recurrent venous thrombosis. The pathomechanisms leading to venous thrombosis in patients with high factor VIII are still unclear. In many patients, however, a biochemically detectable hypercoagulable state (as represented by elevated levels of the coagulation activation marker prothrombin thrombin fragment F1.2) was demonstrated. The optimal duration of secondary thromboprophylaxis for patients with high factor VIII levels is uncertain. We currently perform an interventional trial comparing conventional to extended anticoagulation. Reduction of factor VIII by administration of a non-selective ss-receptor blocker might be a promising therapeutic concept which is currently under investigation.