Factor XI contributes to thrombin generation in the absence of factor XII

Dmitri V. Kravtsov, Anton Matafonov, Erik I. Tucker, Mao Fu Sun, Peter N. Walsh, Andras Gruber, David Gailani

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

During surface-initiated blood coagulation in vitro, activated factor XII (fXIIa) converts factor XI (fXI) to fXIa. Whereas fXI deficiency is associated with a hemorrhagic disorder, factor XII deficiency is not, suggesting that fXI can be activated by other mechanisms in vivo. Thrombin activates fXI, and several studies suggest that fXI promotes coagulation independent of fXII. However, a recent study failed to find evidence for fXII-independent activation of fXI in plasma. Using plasma in which fXII is either inhibited or absent, we show that fXI contributes to plasma thrombin generation when coagulation is initiated with low concentrations of tissue factor, factor Xa, or α-thrombin. The results could not be accounted for by fXIa contamination of the plasma systems. Replacing fXI with recombinant fXI that activates factor IX poorly, or fXI that is activated poorly by thrombin, reduced thrombin generation. An antibody that blocks fXIa activation of factor IX reduced thrombin generation; however, an antibody that specifically interferes with fXI activation by fXIIa did not. The results support a model in which fXI is activated by thrombin or another protease generated early in coagulation, with the resulting fXIa contributing to sustained thrombin generation through activation of factor IX.

Original languageEnglish
Pages (from-to)452-458
Number of pages7
JournalBlood
Volume114
Issue number2
DOIs
Publication statusPublished - 2009
Externally publishedYes

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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  • Cite this

    Kravtsov, D. V., Matafonov, A., Tucker, E. I., Sun, M. F., Walsh, P. N., Gruber, A., & Gailani, D. (2009). Factor XI contributes to thrombin generation in the absence of factor XII. Blood, 114(2), 452-458. https://doi.org/10.1182/blood-2009-02-203604