Does aprotinin influence endothelial-associated coagulation in cardiac surgery?

Abstract

Aprotinin has been reported to reduce bleeding in cardiac surgery patients. Its mechanisms of action on coagulation have not been fully elucidated. In a prospectively randomized study of 40 patients undergoing elective aortocoronary bypass grafting, the influence of high-dose aprotinin (2 million IU of aprotinin before CPB, 500,000 IU/h until the end of operation, 2 million IU added to the prime) (N = 20) on endothelial-related coagulation was compared to a non-treated control group (N = 20). Thrombomodulin (TM), protein C and (free) protein S as well as thrombin/antithrombin-III (TAT) plasma concentrations were measured by enzyme-linked immunosorbent assays (ELISA) before the aprotinin infusion, before cardiopulmonary bypass (CPB), during CPB and after CPB, at the end of surgery, 5 hours after CPB, and on the first postoperative day. All standard coagulation parameters (AT-111 and fibrinogen plasma levels, platelet count, partial thromboplastin time) did not differ between the two groups. At baseline, TM plasma levels were within the normal range (<40 ng/mL) and similar in both groups. During CPB, TM plasma concentrations decreased similarly in both groups (aprotinin: 18 ± 6 ng/mL, control: 17 ± 7 ng/ mL) followed by a comparable increase in the postbypass period until the first postoperative day (aprotinin: 60 ± 10 ng/mL, control: 53 + 11 ng/mL). Protein C and (free) protein S plasma levels also showed no differences between the two groups. On the first postoperative day, baseline values for protein C and protein S had not yet been reached. At the end of surgery, TAT had increased more in the nontreated control (from 8 ± 3 μg/L to 90 ± 12 μg/L) than in the aprotinin-treated patients (from 10 ± 4 ng/L to 68 ± 13 μg/L) ( P < 0.05). Postoperative blood loss and use of homologous blood were not different in either group. It is concluded that aprotinin did not influence endothelial-related coagulation. Neither TM nor protein C or (free) protein S plasma levels were significantly different from a nontreated control group.