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.
Boldt
J
J
Department of Anaesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, Germany.
Schindler
E
E
Welters
I
I
Wittstock
M
M
Stertmann
W A
WA
Hempelmann
G
G
D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000494:pharmacology; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects*; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006493:Heparin / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000378:metabolism; D019106:Postoperative Hemorrhage / Q000209:etiology; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D016037:Single-Blind Method; D018180:Thrombomodulin / Q000378:metabolism
D000925:Anticoagulants; D011486:Protein C; D017293:Protein S; D018180:Thrombomodulin; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases