New antiinflammatory and platelet-preserving effects of aprotinin

The clinical benefit of aprotinin with respect to improved hemostasis, plat elet function, and inflammatory response to cardiopulmonary bypass (CPB) su rgery has been well documented, but these benefits have been overshadowed b y the concern that such a potently hemostatic agent might also be prothromb otic. In this article, we discuss recent advances in the understanding of t he basic mechanism of aprotinin that have led to the identification of new antiinflammatory targets and the discovery that aprotinin is, in fact, anti thrombotic with respect to platelets. Its antithrombotic action is mediated by the selective blocking of the major thrombin receptor, the protease-act ivated receptor 1 (PAR1), but not other receptors of platelet activation (i e, collagen, adenosine diphosphate [ADP], or epinephrine receptors). The se lective targeting of PARI enables aprotinin to protect platelets from unwan ted activation by thrombin generated during CPB surgery (consistent with a role in platelet-preservation), while permitting the participation of plate lets in the formation of hemostatic plugs at wound and suture sites, where collagen, ADP, and epinephrine are most likely to be expressed. Aprotinin t herefore exerts a subtle hemostatic yet antithrombotic mechanism of action, which, when allied with its multitiered antiinflammatory effect, makes thi s drug a valuable companion to cardiac surgery. (C) 2001 by The Society of Thoracic Surgeons.