Effect of low-dose aprotinin on coagulation and fibrinolysis in cardiopulmonary bypass.
To study the effect of low-dose aprotinin on hemostasis in patients undergoing cardiopulmonary bypass (CPB) for coronary artery bypass operations and to elucidate the mechanism of aprotinin action, we randomized 14 of 27 patients to receive 30,000 KIU/kg aprotinin in the CPB priming volume and 7,500 KIU/kg aprotinin intravenously each hour during CPB (1 patient was excluded from the aprotinin group because of protamine shock). Intraoperative and postoperative blood loss was significantly reduced in the aprotinin group. Antithrombin III level was significantly decreased, and the levels of thrombin-antithrombin III complexes were significantly increased during CPB in both groups, indicating activation of the clotting system. The marked increase in fibrin(ogen) degradation products during CPB in the control group, indicating enhanced fibrinolytic activity, was significantly reduced in the aprotinin group. alpha 2-Plasmin inhibitor was significantly reduced during CPB in the control group. The marked increase in alpha 2-plasmin inhibitor-plasmin complexes in the control group, indicating plasmin activity, was significantly reduced in the aprotinin group. A marked decrease in the platelet count was observed during CPB similarly in both groups. These findings demonstrated that low-dose aprotinin administration was effective in reducing intraoperative and postoperative blood loss and that activation of the clotting system during CPB was not followed by hyperfibrinolysis in aprotinin-treated patients. The improved hemostasis is mainly attributable to the prevention of hyperfibrinolysis during CPB.
Kawasuji
M
M
Department of Surgery (I), Kanazawa University School of Medicine, Japan.
Ueyama
K
K
Sakakibara
N
N
Tedoriya
T
T
Matsunaga
Y
Y
Misaki
T
T
Watanabe
Y
Y
D000933:Antifibrinolytic Agents / Q000097:blood; D000990:Antithrombin III / Q000032:analysis; D007611:Aprotinin / Q000008:administration & dosage / Q000627:therapeutic use*; D001777:Blood Coagulation / Q000187:drug effects*; D016063:Blood Loss, Surgical / Q000517:prevention & control; D002315:Cardiopulmonary Bypass; D001026:Coronary Artery Bypass; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005341:Fibrinolysin / Q000032:analysis; D005342:Fibrinolysis / Q000187:drug effects*; D006454:Hemoglobins / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007431:Intraoperative Complications / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010447:Peptide Hydrolases / Q000032:analysis; D010976:Platelet Count / Q000187:drug effects; D000979:alpha-2-Antiplasmin / Q000032:analysis
D000933:Antifibrinolytic Agents; D005338:Fibrin Fibrinogen Degradation Products; D006454:Hemoglobins; D000979:alpha-2-Antiplasmin; C046193:antithrombin III-protease complex; C037742:plasmin-plasmin inhibitor complex; D000990:Antithrombin III; D007611:Aprotinin; D010447:Peptide Hydrolases; D005341:Fibrinolysin