• M Sperzel and J Huetter.
• Product Related Research, Bayer Healthcare AG, Wuppertal, Germany. michael.sperzel@bayerhealthcare.com
• J. Thromb. Haemost. 2007 Oct 1;5(10):2113-8.

BackgroundThe serine protease inhibitor aprotinin and plasminogen inhibitor tranexamic acid are used in coronary artery bypass graft (CABG) surgery to reduce bleeding. Clinicians may consider these agents as readily substitutable regarding their pharmacological profiles.ObjectiveThese agents were evaluated in assays of hemostasis to elucidate their underlying mechanism(s) of action.MethodsIn human plasma, effects on both clot fibrinolysis and coagulation were spectrophotometrically quantified in vitro. Rat-tail bleeding and arteriovenous shunt thrombus formation models were conducted in vivo.ResultsFibrinolysis was inhibited by aprotinin (IC(50), 0.16 +/- 0.02 micromol L(-1)) and tranexamic acid (IC(50), 24.1 +/-1.1 micromol L(-1)). In vivo, aprotinin dose-dependently reduced rat-tail bleeding time (minimal effective dose, 3 mg kg(-1) bolus plus 6 mg kg(-1 )h(-1) infusion); tranexamic acid reduced bleeding time (minimal effective dose, 100 mg kg(-1) h(-1)). In vitro, coagulation time was doubled by aprotinin at 3.2 +/- 0.2 micromol L(-1), while tranexamic acid showed no effect at concentrations up to 3 mmol L(-1). Aprotinin inhibited thrombus formation in vivo in a dose-dependent manner (minimal effective dose, 3 mg kg(-1) bolus plus 6 mg kg(-1) h(-1) infusion). Conversely, tranexamic acid dose-dependently increased thrombus formation and thrombus weight (minimal effective dose, 100 mg kg(-1 )h(-1) infusion).ConclusionsThese data show that aprotinin and tranexamic acid have differential effects on hemostasis and are not necessarily substitutable with respect to mechanism of action. Although both agents have been shown to reduce bleeding in patients undergoing CABG, their divergent effects on thrombus formation observed in vitro and in vivo should be critically evaluated clinically.

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