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Ann Thorac Surg 2001;72:S1808-S1813
© 2001 The Society of Thoracic Surgeons

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Supplement: Mechanisms and attenuation of abnormalities in hemostasis/inflammation and neurologic injury: implications for patient outcomes

New antiinflammatory and platelet-preserving effects of aprotinin

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

* Address reprint requests to Dr Landis, National Heart and Lung Institute, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Du Cane Rd, London, England W12 0NN, United Kingdom
e-mail: r.landis{at}ic.ac.uk

Presented at Mechanisms and Attenutation of Abnormalities in Hemostasis/Inflammation and Neurologic Injury: Implications for Patient Outcomes, Vancouver, BC, Canada, May 6, 2001.

The clinical benefit of aprotinin with respect to improved hemostasis, platelet function, and inflammatory response to cardiopulmonary bypass (CPB) surgery has been well documented, but these benefits have been overshadowed by the concern that such a potently hemostatic agent might also be prothrombotic. In this article, we discuss recent advances in the understanding of the basic mechanism of aprotinin that have led to the identification of new antiinflammatory targets and the discovery that aprotinin is, in fact, antithrombotic with respect to platelets. Its antithrombotic action is mediated by the selective blocking of the major thrombin receptor, the protease-activated receptor 1 (PAR1), but not other receptors of platelet activation (ie, collagen, adenosine diphosphate [ADP], or epinephrine receptors). The selective targeting of PAR1 enables aprotinin to protect platelets from unwanted activation by thrombin generated during CPB surgery (consistent with a role in platelet-preservation), while permitting the participation of platelets in the formation of hemostatic plugs at wound and suture sites, where collagen, ADP, and epinephrine are most likely to be expressed. Aprotinin therefore exerts a subtle hemostatic yet antithrombotic mechanism of action, which, when allied with its multitiered antiinflammatory effect, makes this drug a valuable companion to cardiac surgery.

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