title: Factor V antigen levels and venous thrombosis: risk profile, interaction with factor V leiden, and relation with factor VIII antigen levels.
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.
authors.affiliation: Hemostasis and Thrombosis Research Center, Department of Clinical Epidemiology, Leiden University Medical Center, The Netherlands.
authors.forename: P W
authors.initials: PW
authors.lastname: Kamphuisen
authors.forename: F R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: J C
authors.initials: JC
authors.lastname: Eikenboom
authors.forename: R
authors.initials: R
authors.lastname: Bos
authors.forename: R M
authors.initials: RM
authors.lastname: Bertina
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004351:Drug Resistance; D005165:Factor V / Q000378:metabolism*; D005169:Factor VIII / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011486:Protein C / Q000502:physiology; D012307:Risk Factors; D020246:Venous Thrombosis / Q000097:blood*
chemical_list: D011486:Protein C; C095381:factor V Leiden; D005165:Factor V; D005169:Factor VIII