TAFI

TAFI is a plasma zymogen that, in response to thrombin, and especially thrombin in complex with thrombomodulin is converted to a carboxypeptidase B- like enzyme that attenuates fibrinolysis. Thus, it provides an explicit molecular connection between the coagulation and fibrinolytic cascades, such that activity in the former suppresses activity in the latter. Studies in vitro have shown that both soluble and endothelial cell thrombomodulin stimulate. TAFI activation, with a consequent suppression of clot lysis. In plasma, potentiation of thrombin formation through the intrinsic pathway leads to TAFI activation and retarded fibrinolysis. Thus, bleeding as a result of defects in the intrinsic pathway may, at least in part be due to a lack of suppression of fibrinolysis. Studies performed to date suggest that TAFI is activated and that TAFIa modulates fibrinolysis in vivo. Further work will elucidate further the physiological role of TAFI and TAFIa, and will indicate whether TAFI activation or TAFIa activity can be modulated for therapeutic purposes.