The antithrombotic and antiinflammatory mechanisms of action of aprotinin

Aprotinin (Trasylol) is generally regarded to be an effective hemostatic ag ent that prevents blood loss and preserves platelet function during cardiac surgery procedures requiring cardiopulmonary bypass (CBP). However, its cl inical use has been limited by the concern that such a potent hemostatic ag ent might be prothrombotic, particularly in relation to coronary vein graft occlusion. In this review we present a mechanism of action that challenges such a viewpoint and explains how aprotinin can be simultaneously hemostat ic and antithrombotic. Aprotinin achieves these two apparently disparate pr operties by selectively blocking the proteolytically activated thrombin rec eptor on platelets, the protease-activated receptor 1 (PAR1), while leaving other mechanisms of platelet aggregation unaffected. We also review recent research leading to the discovery of novel antiinflammatory targets for ap rotinin. A better understanding of its mechanisms of action has led to the conclusion that aprotinin is a remarkable drug with the capacity to correct many of the imbalances that develop in the coagulation system and the infl ammatory system after CPB. Nonetheless, it has been clinically underused fo r fear of causing thrombotic complications, a fear that in light of recent evidence may be unfounded. (C) 2001 by The Society of Thoracic Surgeons.