Reduction of blood activation in patients receiving aprotinin during cardiopulmonary bypass for coronary artery surgery.
Aprotinin reduces blood loss after cardiac surgery, particularly in patients taking aspirin. This study was performed to evaluate whether the reduction of contact phase activation by aprotinin is related to decreased complement activation during blood activation. Two hundred patients were prospectively operated on for coronary artery bypass. Aprotinin was used in the cardiopulmonary bypass (CPB) prime if aspirin was not discontinued 10 days before surgery and in patients undergoing second operation (n = 102). Blood loss was significantly reduced in patients receiving aprotinin (596 +/- 309 ml vs 754 +/- 329 ml without aprotinin; p = 0.0001), as was the need for transfusion (13% vs 34% without aprotinin; p = 0.0001) after surgery. Blood activation has been studied in 60 patients. Multivariate analysis showed that contact phase activation, as assessed by maximum values of C1 inhibitor/kallikrein complexes, was reduced by aprotinin treatment (p < 0.0001). Fibrinolytic activity decreased with aprotinin treatment, as reflected by lower values of D-dimers at the end of CPB (p < 0.0001). In addition, thrombin generation, as assessed by F1 + 2 scission peptide, was reduced by aprotinin (p = 0.01). However, the stepwise regression model emphasized that activation of the alternative and classic complement pathways, as reflected by C3b/c and C4b/c levels, was not affected by aprotinin; neither was leukocyte activation, as reflected by elastase release. These results suggest that aprotinin does not combine the reduction of complement activation with the reduced activation of the contact phase, fibrinolysis, or coagulation during CPB for coronary artery surgery.
Baufreton
C
C
Department of Thoracic and Cardiovascular Surgery, Association Claude Bernard, Hôpital Henri Mondor, Créteil, France.
Velthuis
H T
HT
Jansen
P G
PG
Besnerais
P L
PL
Wildevuur
C H
CH
Loisance
D Y
DY
D000368:Aged; D007611:Aprotinin / Q000494:pharmacology*; D001241:Aspirin / Q000009:adverse effects; D001777:Blood Coagulation / Q000187:drug effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003167:Complement Activation / Q000187:drug effects*; D003174:Complement C1 Inactivator Proteins / Q000378:metabolism; D005112:Extracorporeal Circulation / Q000009:adverse effects; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019106:Postoperative Hemorrhage / Q000517:prevention & control; D011446:Prospective Studies
D003174:Complement C1 Inactivator Proteins; D007611:Aprotinin; D007610:Kallikreins; D001241:Aspirin