© 2000 American Heart Association, Inc.
Thrombosis |
Factor V Antigen Levels and Venous Thrombosis
Risk Profile, Interaction With Factor V Leiden, and Relation With Factor VIII Antigen Levels
From the Hemostasis and Thrombosis Research Center (P.W.K., F.R.R., J.C.J.E., R.M.B.) and the Department of Clinical Epidemiology (F.R.R.), Leiden University Medical Center, and the Gaubius Laboratory (R.B.), TNO Prevention and Health, Leiden, the Netherlands. Dr Bos is now at Pharming Technologies, Leiden, the Netherlands.
Correspondence to Rogier M. Bertina, Hemostasis and Thrombosis Research Center, Leiden University Medical Center, C2-R, PO Box 9600, 2300 RC Leiden, Netherlands. E-mail bertina{at}hematology.azi
Abstract—Clotting factor V has a dual function in coagulation: after activation, procoagulant factor V stimulates the formation of thrombin, whereas anticoagulant factor V acts as a cofactor for activated protein C (APC) in the degradation of factor VIII/VIIIa, thereby reducing thrombin formation. In the present study, we evaluated whether plasma factor V levels, either decreased or increased, are associated with venous thrombosis. High procoagulant factor V levels may enhance prothrombinase activity and increase the thrombosis risk. Low anticoagulant factor V levels could reduce APC-cofactor activity in the factor VIII inactivation (APC-resistant phenotype), which might also promote thrombosis. Low factor V levels in combination with factor V Leiden could lead to a more severe APC-resistant phenotype (pseudohomozygous APC resistance). To address these issues, we have measured factor V antigen (factor V:Ag) levels in 474 patients with thrombosis and 474 control subjects that were part of the Leiden Thrombophilia Study (LETS). Factor V:Ag levels increased by 7.6 U/dL for every successive 10 years of age. Mean factor V:Ag levels were 134 (range 41 to 305) U/dL in patients and 132 (range 47 to 302) U/dL in controls. Neither high nor low factor V:Ag levels were associated with venous thrombosis. We found that factor V:Ag and factor VIII antigen levels in plasma were correlated, but factor V did not modify the thrombotic risk of high factor VIII levels. The normalized APC ratio was not influenced by the factor V:Ag level in subjects with or without factor V Leiden. We conclude that neither low nor high factor V:Ag levels are associated with venous thrombosis and that factor V:Ag levels do not mediate the thrombotic risk associated with high factor VIII levels.
Key Words: factor V • venous thrombosis • factor V Leiden • factor VIII
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