Activation of hemostasis during cardiopulmonary bypass and pediatric aprotinin dosage

Cardiopulmonary bypass results in inappropriate activation of the coagulation and fibrinolytic systems. Factors such as a greater degree of hemodilution, use of deep hypothermic circulatory arrest, the impact of cyanosis on coagulation, and the immature coagulation system of the newborn will increase the risk of problematic perioperative bleeding.

This article describes the characteristics of the hemostatic system in children undergoing cardiac operations and addresses the effect of aprotinin on hemostasis. Hemostatic parameters were measured in 96 pediatric patients using three different doses of aprotinin. The high-dose group (group 1) received 30,000 KIU/kg (4.2 mg/kg) of aprotinin after induction of anesthesia and an additional bolus of 30,000 KIU/kg (4.2 mg/kg) into the pump prime. In the low-dose group (group 2), both the initial bolus and the pump-prime dose of aprotinin were halved to 15,000 KIU/kg (2.1 mg/kg). Group 3 received the high dose with an additional bolus of aprotinin to the pump prime.

Plasma levels of aprotinin in both groups 1 and 2 were lower than the 200 KIU/mL (0.03 mg/mL) value usually reached in adults with high-dose aprotinin treatment. Group 3 patients had levels greater than 200 KIU/mL (0.03 mg/mL) throughout the procedure. Biochemical indices of fibrinolysis (fibrin[ogen] degradation products, D-dimers) revealed significant and dose-dependent inhibition at all three aprotinin concentrations. In contrast, significant changes in coagulation activation markers (prothrombin fragments F1.2, thrombin-antithrombin III complex, and fibrin monomers) were found only in group 3.

The inverse relationship between a small patient's blood volume and the large pump-prime volume requires additional aprotinin to be added to the prime to achieve plasma levels sufficient to inhibit activation of the coagulation cascade.