Activation of hemostasis during cardiopulmonary bypass and pediatric aprotinin dosage.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations.

The effect of high-dose aprotinin treatment on hemostatic activation during cardiopulmonary bypass in pediatric patients having cardiac operations was investigated. Sixty patients weighing less than 10 kg undergoing cardiac operations for different types of congenital heart diseases were studied: 20 patients were treated with aprotinin 2 x 15,000 KIU/kg, 20 patients with 2 x 30,000 KIU/kg, and 20 patients without aprotinin treatment served as the control group. Different split products of fibrinogen and/or fibrin and the fibrinolytic activity on fibrin plates were measured to assess fibrinolytic activation. F1/F2 prothrombin fragments, thrombin-antithrombin III-complex, and fibrin monomers were measured to estimate thrombin activation. There was a significant dose-dependent reduction in fibrin-fibrinogen split product formation during cardiopulmonary bypass: In the high-dose aprotinin group the concentration of the split products at the end of bypass was 1.5 +/- 0.6 micrograms/ml, compared with 3.4 +/- 3.0 micrograms/ml in the low-dose aprotinin group and 6.7 +/- 3.5 micrograms/ml in the control group (p < 00.5). Fibrinolytic activation on fibrin plates was also significantly reduced by aprotinin. Fibrin monomer formation was significantly diminished at the end of cardiopulmonary bypass in the high-dose group: 9.2 +/- 5.2 micrograms/ml compared with 21.6 +/- 14 micrograms/ml in the control group (p < 00.5). Elastase in complex with alpha 1-protease inhibitor at the end of bypass was increased to the same amount in the three groups: 784 +/- 278 ng/mL (control group), 693 +/- 189 ng/ml (low-dose aprotinin), and 719 +/- 270 ng/mL (high dose aprotinin) (no significant difference). Blood loss 6 hours postoperatively was significantly (p < 00.5) less in the high-dose group (99 +/- 32 ml/m2) than in the control group (164 +/- 87 ml/m2; low-dose group: 160 +/- 106 ml/m2). These observations suggest an attenuation of hemostatic activation during cardiopulmonary bypass with less plasmin formation and, because of inhibition of contact activation, less thrombin generation with aprotinin treatment. Thus the thrombotic-thrombolytic equilibrium is kept more balanced after cardiopulmonary bypass. High-dose aprotinin treatment is recommended for pediatric patients undergoing cardiac operations.