Abortion
It is concluded that one of the modes of action of aprotinin in reducing blood loss after cardiac surgery may be by reducing the inhibitory effect of heparin on platelet function.
Abstract
including its antifibrinolytic and antiplasmin actions, and also the ability of plasmin and other enzymes to strip platelet glycoprotein lb receptors. We suggest, however, that their conclusion that the efficacy of aprotinin in reducing blood loss after cardiac surgery shows the importance offibrinolytic activation in perioperative bleedingmay be invalid. The problem with this conclusion is that hyperfibrinolysis does not seem to be a major complication of modern cardiopulmonary bypass,23 though this is disputed by some. In addition, the observation that a single dose of aprotinin at the start of a bypass operation is as effective as a continuous infusion in reducing blood loss4 suggests that aprotinin's action against proteases such as plasmin, which are continually produced throughout bypass operations, cannot explain its prohaemostatic action. As the authors note, an acquired platelet defect has been incriminated as a major cause of non-surgical bleeding after cardiopulmonary bypass. We suggest a previously unrecognised aetiology of this defect which may provide an explanation for the prohaemostatic action of aprotinin. This is based on unpublished work carried out at our unit with a new technique (haemostatometry) to assess platelet function.' By using this method in 250 patients we have shown a wide individual variation in in vitro platelet inhibition with heparin at a dose equivalent to that given during cardiopulmonary bypass (about 30% showed severe inhibition). In 100 patients having cardiac surgery the group with severe in vitro platelet inhibition with heparin preoperatively had a significantly greater blood loss than those with moderate platelet inhibition. We also showed in 25 patients that the addition of aprotinin to heparin significantly reduced in vitro platelet inhibition, particularly in the group that had severe platelet inhibition with heparin alone. We conclude that one of the modes of action of aprotinin in reducing blood loss after cardiac surgery may be by reducing the inhibitory effect of heparin on platelet function. LINDSAY C H JOHN