Thrombin activatable fibrinolysis inhibitor

Hamostaseologie. 2011 Aug;31(3):165-6, 168-73. doi: 10.5482/ha-1155. Epub 2011 Jun 1.

Abstract

Thrombin activatable fibrinolysis inhibitor (TAFI) was discovered two decades ago as a consequence of the identification of an unstable carboxypeptidase (CPU), which was formed upon thrombin activation of the respective pro-enzyme (proCPU). The antifibrinolytic function of the activated form (TAFIa, CPU) is directly linked to its capacity to remove C-terminal lysines from the surface of the fibrin clot. No endogenous inhibitors have been identified, but TAFIa activity is regulated by its intrinsic temperature-dependent instability with a half-life of 8 to 15 min at 37 °C. A variety of studies have demonstrated a role for TAFI/TAFIa in venous and arterial diseases. In addition, a role in inflammation and cell migration has been shown. Since an elevated level of TAFIa it is a potential risk factor for thrombotic disorders, many inhibitors, both at the level of activation or at the level of activity, have been developed and were proven to exhibit a profibrinolytic effect in animal models. Pharmacologically active inhibitors of the TAFI/TAFIa system may open new ways for the prevention of thrombotic diseases or for the establishment of adjunctive treatments during thrombolytic therapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Coagulation / immunology*
  • Carboxypeptidase B2 / chemistry*
  • Carboxypeptidase B2 / immunology*
  • Carboxypeptidase B2 / ultrastructure
  • Hemostasis / immunology*
  • Humans
  • Peptide Hydrolases / immunology*
  • Thrombosis / immunology*

Substances

  • Peptide Hydrolases
  • Carboxypeptidase B2