Aprotinin protects platelets against the initial effect of cardiopulmonary bypass

Abstract

Remarkable improvement in hemostasis after cardiopulmonary bypass has been achieved by treatment with the proteinase inhibitor aprotinin, but the mechanism is still unclear. The present study is designed to elucidate the importance of platelet adhesive (glycoprotein Ib) or aggregatory (glycoprotein IIbIIIa) receptors on this hemostatic function in cardiopulmonary bypass and its improvement by aprotinin treatment. To determine whether the first pass of blood through the circuit or a continuous proteolytic attack is the main cause of platelet damage, we gave two different dose regimens of aprotinin treatment to patients undergoing coronary artery bypass grafting. Part I of the study consisted of a double-blind trial on 60 patients. Patients received placebo or aprotinin infusion (total 6.10(6) KIU) before and during bypass. A consecutive group of 22 matching patients received one single bolus of aprotinin in the pump prime (2.10(6) KIU). Blood samples were collected before and during operation to assess the effect of bypass and aprotinin on platelets and the activation of the various proteases in relation to hemostasis expressed in blood loss and blood requirements. The adhesive platelet membrane Ib glycoproteins were decreased by 50% in the untreated patients within 5 minutes of cardiopulmonary bypass and remained low during bypass, whereas glycoprotein Ib did not decrease in either group of aprotinin-treated patients. The platelet membrane IIbIIIa glycoproteins did not significantly change during bypass in either group, but fibrinogen binding to these receptors improved significantly in the 6.10(6) KIU aprotinin-treated group at the end of bypass as compared with initial values. The high continuous dose of 6.10(6) KIU aprotinin inhibited the clotting and kallikrein/kinin system throughout the operation; the pump prime dose of 2.10(6) KIU inhibited these systems only initially. Although the fibrinolytic activity was effectively inhibited in both aprotinin groups, fibrinolytic activity became apparent only at the end phase of bypass in the placebo group. However, improved hemostasis was observed intraoperatively from the start of bypass and resulted in a 40% lower blood loss intraoperatively and postoperatively and consequently a 40% lower total blood requirement in the aprotinin-treated patients than in the untreated patients. Our results therefore demonstrate that the improved hemostasis during and after bypass in patients treated with aprotinin has specifically to be attributed to a preserved adhesive capacity of platelets that was affected in the first pass of blood through the cardiopulmonary bypass circuit.