High Plasma Levels of Factor VIII and the Risk of Recurrent Venous Thromboembolism
Paul A. Kyrle, M.D., Erich Minar, M.D., Mirko Hirschl, M.D., Christine Bialonczyk, M.D., Milena Stain, M.D., Barbara Schneider, Ph.D., Ansgar Weltermann, M.D., Wolfgang Speiser, M.D., Klaus Lechner, M.D., and Sabine Eichinger, M.D.
Background A high plasma level of factor VIII is a risk factorfor venous thromboembolism. We evaluated the risk of a recurrenceof thrombosis after an initial episode of spontaneous venousthromboembolism among patients with high plasma levels of factorVIII.
Methods We studied 360 patients for an average follow-up periodof 30 months after a first episode of venous thromboembolismand discontinuation of oral anticoagulants. Patients who hadrecurrent or secondary venous thromboembolism, a congenitaldeficiency of an anticoagulant, the lupus anticoagulant, hyperhomocysteinemia,cancer, or a requirement for long-term treatment with antithromboticdrugs or who were pregnant were excluded. The end point wasobjectively documented, symptomatic recurrent venous thromboembolism.
Results Recurrent venous thromboembolism developed in 38 ofthe 360 patients (10.6 percent). Patients with recurrence hadhigher mean (±SD) plasma levels of factor VIII than thosewithout recurrence (182±66 vs. 157±54 IU per deciliter,P=0.009). The relative risk of recurrent venous thrombosis was1.08 (95 percent confidence interval, 1.04 to 1.12; P<0.001)for each increase of 10 IU per deciliter in the plasma levelof factor VIII. Among patients with a factor VIII level abovethe 90th percentile of the values in the study population, thelikelihood of recurrence at two years was 37 percent, as comparedwith a 5 percent likelihood among patients with lower levels(P<0.001). Among patients with plasma factor VIII levelsabove the 90th percentile, as compared with those with lowerlevels, the overall relative risk of recurrence was 6.7 (95percent confidence interval, 3.0 to 14.8) after adjustment forage, sex, the presence or absence of factor V Leiden or theG20210A prothrombin mutation, and the duration of oral anticoagulation.
Conclusions Patients with a high plasma level of factor VIIIhave an increased risk of recurrent venous thromboembolism.
Source Information
From the Department of Internal Medicine I, Division of Hematology and Hemostasis (P.A.K., M.S., A.W., K.L., S.E.), the Department of Internal Medicine II, Division of Angiology (E.M.), the Department of Medical Statistics (B.S.), and the Clinical Institute of Medical and Chemical Laboratory Diagnostics (W.S.), Vienna University Hospital; Hanuschkrankenhaus (M.H.); and Wilhelminenspital (C.B.) all in Vienna, Austria.
Address reprint requests to Dr. Kyrle at the Allgemeines Krankenhaus Wien, Klinik für Innere Medizin I, Abteilung für Hämatologie und Hämostaseologie, Währinger Gürtel 1820, A-1090 Vienna, Austria, or at paul.kyrle{at}akh-wien.ac.at.
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