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Ann Thorac Surg 2001;72:2169-2175
© 2001 The Society of Thoracic Surgeons

Review

The antithrombotic and antiinflammatory mechanisms of action of aprotinin

R. Clive Landis, PhD*a, George Asimakopoulos, FRCSb, Mike Poullis, FRCSb, Dorian O. Haskard, FRCPa, Kenneth M. Taylor, FRCSb

a The British Heart Foundation Unit of Cardiovascular Medicine, Hammersmith Hospital, National Heart and Lung Institute, Imperial College School of Medicine, London, England, United Kingdom
b The British Heart Foundation Unit of Cardiac Surgery, Hammersmith Hospital, National Heart and Lung Institute, Imperial College School of Medicine, London, England, United Kingdom

* Address reprint requests to Dr Landis, BHF Cardiovascular Medicine Unit, National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London, England W12 0NN, UK
e-mail: r.landis{at}ic.ac.uk

Aprotinin (Trasylol) is generally regarded to be an effective hemostatic agent that prevents blood loss and preserves platelet function during cardiac surgery procedures requiring cardiopulmonary bypass (CBP). However, its clinical use has been limited by the concern that such a potent hemostatic agent 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 hemostatic and antithrombotic. Aprotinin achieves these two apparently disparate properties by selectively blocking the proteolytically activated thrombin receptor 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 aprotinin. 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 inflammatory system after CPB. Nonetheless, it has been clinically underused for fear of causing thrombotic complications, a fear that in light of recent evidence may be unfounded.




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