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Thromb Haemost 2015; 113(03): 599-604
DOI: 10.1160/TH14-06-0515
Coagulation and Fibrinolysis
Schattauer GmbH

Polyphosphate accelerates factor V activation by factor XIa

Sharon H. Choi   *
1   Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
,
Stephanie A. Smith   *
1   Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
,
James H. Morrissey
1   Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
› Author Affiliations Financial support: This work was supported by grants R01 HL047014, F30 HL107089, and UM1 HL120877 from the National Health Lung and Blood Institute of the NIH.
Further Information

Publication History

Received: 13 June 2014

Accepted after major revision: 16 September 2014

Publication Date:
17 November 2017 (online)

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Summary

Factor Va enhances the rate of prothrombin activation by factor Xa by four to five orders of magnitude. Production of initiating levels of factor Va from its precursor, factor V, is a critical event early in haemostasis, as factor V exhibits negligible cofactor activity. While thrombin is the most potent physiological back-activator of factor V, the first prothrombinase complexes require a source of factor Va prior to thrombin generation. A recent study by Whelihan et al. (J Thromb Haemost 2010; 8:1532–1539) identified factor XIa as a candidate for the initial thrombin-independent activation of factor V, although this reaction was slow and required relatively high concentrations of factors V and XIa. Activated platelets secrete polyphosphate, which we previously showed to be potently procoagulant. We now report that polyphosphate greatly accelerates factor V activation by factor XIa, and that this is supported by polyphosphate polymers of the size secreted by activated human platelets. This finding provides additional evidence that factor XIa-mediated generation of factor Va may contribute to the initiation of haemostasis.

Keywords

Polyphosphate - factor V - factor XI - prothrombinase

* These authors contributed equally to this work.


 

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