Activation of factor XI by products of prothrombin activation

作者：Matafonov Anton; Sarilla Suryakala; Sun Mao fu; Sheehan John P; Serebrov Vladimir; Verhamme Ingrid M; Gailani David^*

来源：Blood, 2011, 118(2): 437-445.

DOI：10.1182/blood-2010-10-312983

The prothrombinase complex converts prothrombin to alpha-thrombin through the intermediate meizothrombin (Mz-IIa). Both alpha-thrombin and Mz-IIa catalyze factor (F) XI activation to FXIa, which sustains alpha-thrombin production through activation of FIX. The interaction with FXI is thought to involve thrombin anion binding exosite (ABE) I. alpha-Thrombin can undergo additional proteolysis to beta-thrombin and gamma-thrombin, neither of which have an intact ABE I. In a purified protein system, FXI is activated by beta-thrombin or gamma-thrombin, and by alpha-thrombin in the presence of the ABE I-blocking peptide hirugen, indicating that a fully formed ABE I is not absolutely required for FXI activation. In a FXI-dependent plasma thrombin generation assay, beta-thrombin, gamma-thrombin, and alpha-thrombins with mutations in ABE I are approximately 2-fold more potent initiators of thrombin generation than alpha-thrombin or Mz-IIa, possibly because fibrinogen, which binds to ABE I, competes poorly with FXI for forms of thrombin lacking ABE I. In addition, FXIa can activate factor FXII, which could contribute to thrombin generation through FXIIa-mediated FXI activation. The data indicate that forms of thrombin other than alpha-thrombin contribute directly to feedback activation of FXI in plasma and suggest that FXIa may provide a link between tissue factor-initiated coagulation and the proteases of the contact system. (Blood. 2011; 118(2): 437-445)

• 出版日期2011-7-14