title: Factor V is an anticoagulant cofactor for activated protein C during inactivation of factor Va.
abstract: Coagulation factor V (FV) promotes inactivation of activated factor VIII (FVIIIa) by activated protein C (APC) and protein S. Loss of this APC cofactor activity is proposed to be partially responsible for the APC resistance phenotype of FV(Leiden). However, FVIIIa loses activity rapidly due to dissociation of the A2 domain, and this may be the primary mechanism of FVIIIa inactivation. APC/protein S also readily inactivates activated FV (FVa). We therefore hypothesized that FV can function as an anticoagulant cofactor for APC/protein S in the inactivation of FVa. FV was titrated into FV-deficient plasma, and the APC sensitivity ratio (APCsr; a measure of APC activity) was measured in a clotting assay that was not sensitive to FVIII. Our results showed an increase in APCsr as the FV concentration increased, suggesting an anticoagulant function for FV in this assay. FV(Leiden) showed APC resistance with an APCsr of 1.0. Therefore, under our experimental conditions, FV acted as an anticoagulant cofactor for APC in the inactivation of FVa.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, Calif., USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Cramer
authors.forename: John H
authors.initials: JH
authors.lastname: Griffin
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Gale
mesh_terms: D001777:Blood Coagulation / Q000502:physiology*; D005165:Factor V / Q000235:genetics / Q000378:metabolism*; D015944:Factor VIIIa / Q000378:metabolism; D015943:Factor Va / Q000378:metabolism*; D006801:Humans; D010641:Phenotype; D011486:Protein C / Q000378:metabolism*; D017293:Protein S / Q000378:metabolism; D011517:Prothrombin Time
chemical_list: D011486:Protein C; D017293:Protein S; C095381:factor V Leiden; D015943:Factor Va; D015944:Factor VIIIa; D005165:Factor V