Factor V Is an Anticoagulant Cofactor for Activated Protein C during Inactivation of Factor Va
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چکیده
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. Copyright © 2010 S. Karger AG, Basel Received: January 19, 2010 Accepted after revision: March 24, 2010 Published online: May 22, 2010 Andrew J. Gale Department of Molecular and Experimental Medicine The Scripps Research Institute, MEM-286 10550 N. Torrey Pines Road, La Jolla, CA 92037 (USA) Tel. +1 858 784 2177, Fax +1 858 784 2054, E-Mail agale @ scripps.edu © 2010 S. Karger AG, Basel Accessible online at: www.karger.com/pht D ow nl oa de d by : 54 .1 91 .4 0. 80 9 /1 6/ 20 17 8 :1 9: 14 P M
منابع مشابه
Factor V is an anticoagulant cofactor for activated protein C during inactivation of factor Va.
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/prote...
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