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.