Intraoperative administration of the proteinase Inhibitor aprotinin causes reduction in blood loss and homologous blood requirement in patients undergoing cardiac surgery. To ascertain the blood-saving effect of aprotinin and to obtain further information about the mode of action, 40 patients undergoing primary myocardial revascularization were randomly assigned to receive either aprotinin or placebo treatment. Aprotinin was given as a bolus of 2 X 105 kallikrein inactivator units (KIU) before surgery followed by a continuous infusion of 5 X 105 KIU/h during surgery. Additionally, 2 X 105 KIU were added to the pump prime. Strict criteria were used to obtain a homogeneous patient selection. Total blood loss was reduced from 1,431 +/- 760 ml in the control group to 738 +/- 411 ml in the aprotinin group (P < 0.05) and the homologous blood requirement from 838 +/- 963 ml to 163 +/- 308 ml (P < 0.05). In the control group, 2.3 +/- 2.2 U of homologous blood or blood products were given, and in the aprotinin group, 0.63 +/- 0.96 U were given (P < 0.05). Twenty-five percent of patients in the control group and 63% in the aprotinin group did not receive banked blood or homologous blood products. The activated clotting time as an indicator of inhibition of the contact phase of coagulation was significantly Increased before heparinization in the aprotinin group (141 +/- 13 s vs. 122 +/- 25 s) and remained significantly Increased until heparin was neutralized after cardiopulmonary bypass (CPB). The concentration of the thrombin-antithrombin III complex was significantly decreased at the end of CPB in the aprotinin group, indicating less thrombin generation in the aprotinin-treated group. The total concentration of the fibrinogen-fibrin split products (FSP) and the split products of the cross-linked fibrin (D-dimers) were also significantly reduced due to attenuated proteolytic activities of thrombin and plasmin. The results of the fibrin plate assay revealed higher fibrinolytic activity during CPB in the control group. The results demonstrate the beneficial effect of high-dose aprotinin treatment on blood loss and homologous blood requirement. This effect can be attributed to the inhibition of the contact phase of coagulation and the consequently reduced thrombotic and fibrionolytic activity during and after CPB
