Influence of High- and Low-Dose Aprotinin on Activation of Hemostasis in Open Heart Operations

Background. The protease inhibitor aprotinin reduces hemostatic activation and blood loss after cardiac operations. The aim of the present study was to investigate the influence of two different aprotinin doses on hemostatic activation and to identify the most effective dose to reduce the postoperative bleeding tendency. Methods. In a prospective, randomized, double-blind clinical trial, 230 patients scheduled for routine open heart operations received either high-dose (group H) or low-dose (group L) aprotinin. Primary outcome measures were the level of F1+2 prothrombin fragments as a marker of thrombin generation, the level of d-dimers as an indicator of fibrinolysis, and the amount of postoperative blood loss. Allogeneic blood transfusion was recorded as a secondary outcome measure. Results. Aprotinin plasma concentrations 5 minutes after the onset of cardiopulmonary bypass were 166 ± 45 kallikrein inactivator units per milliliter in group H and 118 ± 30 kallikrein inactivator units per milliliter in group L (p < 0.05). Fibrinolytic activation was reduced significantly in group H compared with group L: the level of d-dimers at the end of CPB was 1,027 ± 781 ng/mL and 1,977 ± 1,001 ng/mL, respectively, in the two groups (p < 0.05). However, thrombin generation (F1+2 fragments) did not differ between the two groups (7.4 ± 3.5 nmol/L in group H and 8.6 ± 4.3 nmol/L in group L). Twenty-four–hour postoperative blood loss was 663 ± 461 mL in group H compared with 877 ± 513 mL in group L (p < 0.05), and the corresponding allogeneic blood requirement was 1.3 ± 1.9 U in group H and 1.9 ± 2.3 U in group L (p < 0.05). Conclusions. A high-dose aprotinin regimen was significantly more effective than a low-dose regimen in attenuating fibrinolysis and reducing the bleeding tendency and allogeneic blood requirements, but not in reducing F1+2 prothrombin fragments. High-dose aprotinin therapy appears to be superior to low-dose therapy.