Factor V antigen levels and venous thrombosis - Risk profile, interaction with factor V Leiden, and relation with factor VIII antigen levels

Clotting factor V has a dual function in coagulation: after activation, pro coagulant factor V stimulates the formation of thrombin, whereas anticoagul ant factor V acts as a cofactor for activated protein C (APC) in the degrad ation of factor VIII/VIIIa, thereby reducing thrombin formation. In the pre sent study, we evaluated whether plasma factor V levels, either decreased o r increased, are associated with venous thrombosis. High procoagulant facto r 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 Leide n could lead to a more severe APC-resistant phenotype (pseudohomozygous APC resistance). To address these issues, we have measured factor V antigen (f actor V:AE) levels in 474 patients with thrombosis and 474 control subjects that were part of the Leiden Thrombophilia Study (LETS). Factor V:Ag level s increased by 7.6 U/dL for every successive 10 years of age. Mean factor V :AE 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 associ ated with venous thrombosis. We found that factor V:Ag and factor VIII anti gen levels in plasma were correlated, but factor V did not modify the throm botic risk of high factor VIII levels. The normalized APC ratio was not inf luenced by the factor V:Ag level in subjects with or without factor V Leide n. 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 throm botic risk associated with high factor VIII levels.