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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Evaluation of aprotinin and tranexamic acid in different in vitro and in vivo models of fibrinolysis, coagulation and thrombus formation.

BACKGROUND: The 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. OBJECTIVE: These agents were evaluated in assays of hemostasis to elucidate their underlying mechanism(s) of action. METHODS: In 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. RESULTS: Fibrinolysis 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). CONCLUSIONS: These 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.[1]

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