APROTININ IN PERSPECTIVE

Aprotinin is a nonspecific serine protease inhibitor extracted from bovine lung. It was first used during cardiopulmonary bypass to inhibit plasmin-induced complement activation. By chance significant reductions of blood loss and blood requirements were noted in treated patients. Subsequent investigation showed improved hemostasis to result from protection of platelet adhesive receptors (Gp Ib) at the onset of cardiopulmonary bypass. Without aprotinin the contact system of plasma is massively activated on first passage through the cardiopulmonary bypass circuit. Activation of the intrinsic coagulation pathway causes thrombin formation, which impairs platelet adhesive function. Aprotinin blocks contact activation of the kallekrein system during cardiopulmonary bypass and in synergy with heparin prevents thrombin formation through inhibition of the intrinsic clotting cascade. It is likely that neither thrombin nor platelets become involved in the blood-foreign surface contact activation process in aprotinin-treated patients. The fact that the hemostatic process is affected from the very beginning of cardiopulmonary bypass is substantiated by the fact that low-dose aprotinin therapy (2 X 10(6) KIU aprotinin added to the pump prime) leads to the same preservative effect on Gp Ib receptors and blood loss as continuous high-dose infusion (6 x 10(6) KIU) throughout the whole surgical procedure. In the presence of heparin aprotinin prolongs the activated clotting time and the in vitro activated partial thromboplastin time. This has important implications for heparin dosage. An inhibitory effect on the endothelial cell anticoagulant function may also have consequences during hypothermic low flow and circulatory arrest states. Early clinical trials in patients undergoing first operations or reoperations for coronary artery disease confirmed the hemostatic and blood-sparing properties with no apparent adverse effects. Consequently some workers recommend routine use of this agent in every patient undergoing cardiopulmonary bypass. However, evidence is now accumulating to suggest that aprotinin increases the risk of perioperative myocardial infarction during coronary operations and has other potentially fatal adverse effects in certain other groups of patients. In view of these findings a logical approach to the use of aprotinin must be considered.