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Thromb Haemost 2012; 107(01): 15-21
DOI: 10.1160/TH11-06-0431
Review Article
Schattauer GmbH

The anticoagulant function of coagulation factor V

Thomas J. Cramer
1   Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
,
Andrew J. Gale
1   Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
› Author Affiliations Financial support: This study was supported by The Stein Endowment Fund.
Further Information

Publication History

Received: 24 June 2011

Accepted after major revision: 24 October 2011

Publication Date:
20 November 2017 (online)

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Summary

Almost two decades ago an anticoagulant function of factor V (FV) was discovered, as an anticoagulant cofactor for activated protein C (APC). A natural mutant of FV in which the R506 inactivation site was mutated to Gln (FVLeiden) was inactivated slower by APC, but also could not function as anticoagulant cofactor for APC in the inactivation of activated factor VIII (FVIIIa). This mutation is prevalent in populations of Caucasian descent, and increases the chance of thrombotic events in carriers. Characterisation of the FV anticoagulant effect has elucidated multiple properties of the anticoagulant function of FV: 1) Cleavage of FV at position 506 by APC is required for anticoagulant function. 2) The C-terminal part of the FV B domain is required and the B domain must have an intact connection with the A3 domain of FV. 3) FV must be bound to a negatively charged phospholipid membrane. 4) Protein S also needs to be present. 5) FV acts as a cofactor for inactivation of both FVa and FVIIIa. 6) The prothrombotic function of FVLeiden is a function of both reduced APC cofactor activity and resistance of FVa to APC inactivation. However, detailed structural and mechanistic properties remain to be further explored.

Keywords

Activated protein C - anticoagulant - APC resistance - factor V - protein S
 

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