Polyphosphate accelerates factor V activation by factor XIa

Sharon H. Choi, Stephanie A. Smith, James H. Morrissey

Research output: Contribution to journalArticle

Abstract

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 haemo-stasis, 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 Hae-most 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 poly-phosphate 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.

Original languageEnglish (US)
Pages (from-to)599-604
Number of pages6
JournalThrombosis and Haemostasis
Volume113
Issue number3
DOIs
StatePublished - 2015

Keywords

  • Factor V
  • Factor XI
  • Polyphosphate
  • Prothrombinase

ASJC Scopus subject areas

  • Hematology

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