Aprotinin in cardiopulmonary bypass--effects on the Hageman factor (FXII)--Kallikrein system and blood loss.
Aprotinin has been used in our hospital in open heart surgery for almost 20 years and recently published studies have revealed a reduction in postoperative blood loss under this therapy. In the present study patients undergoing aorto-coronary bypass operations received either 20,000 KIU aprotinin/kg body weight (group 2) or 60,000 KIU aprotinin/kg body weight (group 3). Another group of patients without aprotinin served as a control (group 1) and postoperative bleeding was more pronounced in these patients compared with the other groups. In parallel, slight reductions in kallikrein-like activity were observed in patients treated with aprotinin. Furthermore, we have shown that the main inhibitor of the contact phase, C1-esterase-inhibitor, loses some of its activity against beta-FXIIa in the presence of heparin. Aprotinin was able to partly antagonize this phenomenon. All studies dealing with the effect of aprotinin in extracorporeal circulation demonstrate hyperfibrinolysis in untreated patients. Aprotinin is known to inhibit plasmin at low concentrations and thus reduced the postoperative bleeding tendency (group 2). In addition, plasma kallikrein is inhibited by high aprotinin concentrations and is responsible for a reduced activation of the contact phase system. This effect led to a further reduction in blood loss (group 3).
Fuhrer
G
G
Chir. Klinik, Kreiskrankenhaus Reutlingen, Germany.
Gallimore
M J
MJ
Heller
W
W
Hoffmeister
H E
HE
D007611:Aprotinin / Q000494:pharmacology*; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D005174:Factor XII / Q000378:metabolism*; D015956:Factor XIIa / Q000037:antagonists & inhibitors; D006801:Humans; D016234:Kallikrein-Kinin System / Q000187:drug effects*; D007610:Kallikreins / Q000037:antagonists & inhibitors; D011288:Prekallikrein / Q000378:metabolism
D005174:Factor XII; D011288:Prekallikrein; D007611:Aprotinin; D007610:Kallikreins; D015956:Factor XIIa