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Inhibitors of Tissue Factor/Factor VIIa

  • K. P. Gallagher
  • T. E. Mertz
  • L. Chi
  • J. R. Rubin
  • A. C. G. Uprichard
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 132)

Abstract

Tissue factor (TF) is the prime mover in the coagulation cascade. Unlike other factors in the cascade which circulate in the plasma, TF is anchored in the membrane of cells. It has a large extracellular domain to which FVII binds, a single transmembrane domain and a small intracellular domain. In contrast to other elements of the coagulation cascade, no cleavage of TF occurs to activate enzymatic activity. Rather TF provides a scaffold for FVII that also activates and/or amplifies the actions of this factor initiating the extrinsic pathway of coagulation. The TF/VIIa complex activates FX to FXa which, as part of the prothrombinase complex, activates prothrombin to thrombin. The amounts of factor Xa and thrombin generated by the extrinsic pathway are relatively small but the thrombin so produced recruits the coagulation factors in the intrinsic pathway which dramatically amplify formation of additional thrombin and, thereby, fibrin. Although the TF/VIIa complex is not directly responsible for the production of all of the thrombin needed to form a complete thrombus, it plays the crucial role of initiating the process.

Keywords

Tissue Factor Disseminate Intravascular Coagulation Tissue Factor Pathway Inhibitor Kunitz Domain Human Tissue Factor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • K. P. Gallagher
  • T. E. Mertz
  • L. Chi
  • J. R. Rubin
  • A. C. G. Uprichard

There are no affiliations available

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