Aprotinin in orthotopic liver transplantation: Evidence for a prohemostatic, but not a prothrombotic, effect

Aprotinin reduces blood transfusion requirements in orthotopic liver transp lantation (OLT). Concern has been voiced about the potential risk for throm botic complications when aprotinin is used. The aim of this study is to eva luate the effects of aprotinin on the two components of the hemostatic syst em (coagulation and fibrinolysis) in patients undergoing OLT. As part of a larger, randomized, double-blind, placebo-controlled study, we compared coa gulation (fibrinogen level, activated partial thromboplastin time [aPTT], p rothrombin time, and platelet count) and fibrinolytic variables (tissue-typ e plasminogen activator [tPA] antigen and activity, plasminogen activator i nhibitor activity, and D-dimer), as well as thromboelastography (reaction t ime [r], clot formation time, and maximum amplitude) in 27 patients adminis tered either high-dose aprotinin (2 X 10(6) kallikrein inhibitor units [KIU ] at induction, continuous infusion of I X 106 KIU/h, and 1 X 10(6) KIU bef ore reperfusion; n = 10), regular-dose aprotinin (2 X 106 KIU at induction and continuous infusion of 0.5 X 10(6) KIU/h; n = 8), or placebo (n = 9) du ring OLT. Blood samples were drawn at seven standardized intraoperative tim es. Baseline characteristics were similar for the three groups. During the anhepatic and postreperfusion periods, fibrinolytic activity (plasma D-dime r and tPA antigen levels) was significantly lower in aprotinin-treated pati ents compared with the placebo group. Interestingly, coagulation times (aPT T and r) were significantly more prolonged in aprotinin-treated patients th an the placebo group. No difference was seen in the incidence of perioperat ive thrombotic complications in the entire study population (n = 137). Apro tinin has an anticoagulant rather than a procoagulant effect. Its blood-spa ring (prohemostatic) effect appears to be the overall result of a strong an tifibrinolytic and a weaker anticoagulant effect. These findings argue agai nst a prothrombotic effect of aprotinin in patients undergoing OLT.