Mechanism of the preserving effect of aprotinin on platelet function and its use in cardiac surgery.

The deficiency of platelet function is the main defect of the hemostatic mechanism during cardiopulmonary bypass, which greatly exacerbates the postoperative bleeding complications. In this study, we assessed, from basic and clinical perspectives, the mechanism of relieving platelet damage by means of aprotinin. In vitro research confirmed that the addition of urokinase (40 U/ml) to platelet-rich plasma and the addition of plasmin (0.3 U/ml) to washed platelets made ristocetin-induced agglutination decline to 31.6% and 38.5% of control values, respectively. The extent of decline was positively correlated with the concentration of urokinase and plasmin. In addition, the platelet membrane glycoprotein Ib decreased to 76.4% of control value. With the addition of urokinase or plasmin to aprotinin-pretreated platelet-rich plasma or washed platelets, the changes in agglutination are not statistically significant and the decrement in glycoprotein Ib is much less marked. Further in vivo research revealed that cardiopulmonary bypass caused a decrease in plasma alpha 2-antiplasmin, indicating the fibrinolytic system activation. Meanwhile, ristocetin-induced agglutination decreased to 39.6% and platelet glycoprotein Ib decreased to 50% of preoperative values. However, with the administration of aprotinin, plasma alpha 2-antiplasmin during cardiopulmonary bypass did not change; platelet agglutination was improved, platelet glycoprotein Ib was preserved, and this consequently resulted in 46% lower blood loss after the operation. The results showed that fibrinolysis impaired platelet function, and this effect may be associated with the hydrolysis of glycoprotein Ib. Fibrinolytic activation occurred during cardiopulmonary bypass and contributed to postoperative platelet dysfunction to a great extent. Aprotinin may inhibit fibrinolysis during cardiopulmonary bypass and thus relieve the platelet damage and improve the postoperative hemostatic mechanism.