Characterization of thrombin activatable fibrinolysis inhibitor in normal and acquired haemostatic dysfunction

Abstract

Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, which is synthesized in the liver and circulates in the blood at a concentration of about 275 nmol/l. Once activated, by thrombin or plasmin, TAFI down regulates fibrinolysis, slowing clot lysis by cleaving the C-terminal lysine and arginine residues from partially degraded fibrin. Thrombomodulin enhances thrombin activation of TAFI by more than 1000-fold, suggesting that the thrombin-thrombomodulin complex is the physiological activator of TAFI. Activated protein C can up-regulate fibrinolysis by limiting the activation of TAFI via the attenuation of thrombin production. While impairment of fibrinolysis may predispose to thrombosis, excessive fibrinolysis may result in a bleeding tendency. In acquired coagulopathies, TAFI antigen levels are reduced in patients with disseminated intravascular coagulation. In focusing on women with major post-partum haemorrhage requiring blood transfusion, a significant reduction in TAFI levels is observed. The precise degree of TAFI activation is currently being characterized using new and more specific assays. The resulting data may provide insight into therapeutic options to treat post-partum haemorrhage, which is associated with significant morbidity.