TAFI: A Potential Target for Fibrinolytic Drugs

Abstract

Thrombosis is one the major cause of death worldwide. Clinicians and haematologists are confronted more and more with diagnosis and management of patients with venous and arterial thrombo-embolic phenomenon. In the recent past there have been major advancements in the field of the aetio-pathogenisis of haemostasis. Thrombosis occurs when there is an imbalance between pro-thrombotic and anti-thrombotic mechanisms. Thrombin activatable fibrinolysis inhibitor (TAFI) is a potential target to treat various thrombotic as well as metabolic disorders. TAFI is a Carboxypeptidase B like enzyme with a mol. wt. 60 kDa and it is activated by thrombin-thrombomodulin complex to activated form TAFIa which cleaves carboxyl-terminal lysine residues from partially degraded fibrin, rendering it resistant to fibrinolysis by endogenous tissue plasminogen activator (tPA). Thus inhibition of TAFI with an appropriate TAFI inhibitor will be an attractive strategy for various thrombotic as well as metabolic disorders in which levels of TAFI is highly elevated like deep vein thrombosis, angina pectoris, obesity and non insulin dependent diabetes mellitus.