Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia?

Clin Chim Acta. 2007 Mar;378(1-2):1-6. doi: 10.1016/j.cca.2006.10.014. Epub 2006 Oct 26.

Abstract

Pre-eclampsia (P-Ec) is a complex multisystem disorder of unknown aetiology reported to occur in about 6% to 8% of all pregnancies throughout the world. This disease is associated with fibrin deposition and occlusive lesions in placental vessels. Pro-thrombin activatable fibrinolysis inhibitor (pro-TAFI) is a relatively recently described glycoprotein that can be converted into its active form (TAFIa) by thrombin, thrombin-thrombomodulin and plasmin. TAFIa potentially inhibits fibrinolysis by removing C-terminal lysine and arginine residues from fibrin. These residues are required for adsorption of tissue-type plasminogen activator (t-PA) and plasminogen to fibrin. Therefore, TAFIa decreases plasmin formation and protects the fibrin clot against lysis. An increased of pro-TAFI/TAFIa levels has been reported in some clinical conditions associated with thrombotic tendency, as type II diabetes mellitus, deep vein thrombosis and symptomatic artery disease. Few studies have investigated pro-TAFI/TAFIa in normal or complicated pregnancy but contrasting results were reported. Understanding the role of pro-TAFI/TAFIa in the pathogenesis of P-Ec can hold great promise for improving P-Ec management. In this context, a large-scale study evaluating plasma TAFI antigen and activity, its synthesis and metabolism in pre-eclamptic women is required. Recently new selective TAFIa inhibitors have been developed. The design of a new therapy to treat and/or prevent P-Ec, based on successful use of TAFIa inhibitors, may have significant clinical ramifications.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Carboxypeptidase B2 / blood
  • Carboxypeptidase B2 / genetics
  • Carboxypeptidase B2 / physiology*
  • Female
  • Humans
  • Polymorphism, Genetic
  • Pre-Eclampsia / etiology*
  • Pregnancy
  • Protein C / metabolism
  • Protein Precursors / biosynthesis
  • Thrombin / physiology
  • Thrombomodulin / physiology

Substances

  • Protein C
  • Protein Precursors
  • Thrombomodulin
  • Carboxypeptidase B2
  • Thrombin