The effect of the anticoagulation regimen on endothelial-related coagulation in cardiac surgery patients.

Heparin is still the most commonly used anticoagulant in cardiac surgery necessitating cardiopulmonary bypass. In recent years, endothelial-related coagulation (e.g. thrombomodulin/protein C-system) has enlarged our knowledge of the regulation of haemostasis. In a controlled randomised study, the influence of different regimens of anticoagulation on the thrombomodulin/protein C-system was studied. Sixty patients undergoing elective coronary artery bypass grafting were randomly allocated into four groups (n = 15) to receive: 300 IU.kg-1 of heparin before bypass; 600 IU.kg-1 of heparin; 300 IU.kg-1 of heparin as bolus followed by a continuous infusion of 10 000 IU.h-1 until the end of bypass; or 600 IU.kg-1 of heparin plus 'high dose' aprotinin (2 million IU of aprotinin before bypass, 500 000 IU.h-1 until the end of the operation and 2 million IU added to the bypass pump prime). Grouping was blinded for the surgeon and the anaesthetist. Plasma concentrations of thrombomodulin, protein C and (free) protein S as well as thrombin/antithrombin III were measured by enzyme-linked-immunosorbent assays after induction of anaesthesia, during and after bypass, at the end of surgery, 5 h after bypass, and on the first postoperative day. Activated clotting time was significantly longer during bypass in group 2 (566 (60)s) and group 4 (655 (59)s), whereas standard coagulation parameters showed no differences between the four groups. Blood loss and use of homologous blood and blood products were highest in groups 2 and 3. Thrombomodulin plasma levels were similar (and normal) at baseline (< 40 ng.l-1), decreased during bypass and reached baseline values postoperatively without showing significant group differences. Protein C did not show any differences among the groups within the investigation period. 'Free' protein S plasma levels were most reduced in group 1 (from 68 (8)% to 48 (9)% after bypass). Thrombin/antithrombin III plasma concentrations increased most in groups 1 (to 69 (14) micrograms.l-1 after bypass) and 2 (to 48 (7) micrograms.l-1 after bypass), whereas they remained significantly lower in groups 3 and 4. The thrombomodulin/protein C-system was not significantly influenced by the regimen of anticoagulation. Administration of 'high-dose' heparin was associated with the highest blood loss, which could not be related to endothelial-associated coagulation.