The Impact of Aprotinin on Transfusion Requirements in Orthotopic Liver Transplantation

SUMMARY Perioperative blood loss has been identified as an important cause of morbidity and mortality after orthotopic liver transplantation (OLT). Although rare, excessive blood loss is still a serious complication and risk factor for poor outcome after OLT. Besides the surgical skills, specific coagulation abnormalities and disturbances in the hemostatic system contribute to increased blood loss. Hyperfibrinolysis, frequently observed in the anhepatic and early postreperfusion period, may play a significant role. Antifibrinolytic drugs (epsilon aminocaproic acid, tranexamic acid, aprotinin) have the ability to reduce hyperfibrinolysis. This overview discusses the role of one of these antifibrinolytics, aprotinin, in reducing hyperfibrinolysis and thus blood loss during OLT. Several studies have been performed since the early 1990s. In particular, the results of the most recent randomized controlled trials are evaluated. In these studies, a significant reduction in blood loss (40–60%) and transfusion requirements (30–40%) is observed, depending on the administered regimens. Several dose regimens have been used: low‐dose, regular‐dose and high‐dose aprotinin. All three regimens seem to be effective when compared to placebo. At first sight, a low‐dose regimen would therefore be preferable. Other arguments, however, like a dose‐dependent anticoagulant effect, might count in favor of a higher dose. A definite conclusion on the most favorable dose regimen can therefore not be drawn at this moment. The concern for thromboembolic complications associated with the use of aprotinin is discussed. We analyzed the thromboembolic complications in the most recent trials and also combined the data to see if there was any sign for a higher incidence of thromboembolic complications. Results showed no difference between the aprotinin and placebo groups. Moreover, a trend towards a lower incidence of thromboembolic complications was observed in the aprotinin groups, supporting its mild anticoagulant effect. It is concluded that aprotinin is a safe prohemostatic drug which reduces blood loss and transfusion requirements. Despite the relatively low transfusion needs recently described by experienced centers, a positive effect of aprotinin can still be obtained as shown in the most recent studies.