Modes of action

The effects of aprotinin on the coagulation cascade are dependent on the circulating plasma concentrations (expressed as kallikrein inactivation units — kIU/ml) since the affinity of aprotinin for plasmin is significantly greater than that for plasma kallikrein. At a plasma level of 125kIU/ml aprotinin inhibits fibrinolysis and complement activation. Inhibition of plasma kallikrein requires higher doses to provide plasma levels of 250-500kIU/ml.

• Plasma kallikrein inhibition — reduces blood coagulation mediated via contact with anionic surfaces and, in the critically ill patient, improves circulatory stability via reduced kinin activation.

• Prevention of inappropriate platelet activation — neutrophil activation (complement or kallikrein mediated) causes a secondary activation of platelets. Important in this platelet-neutrophil interaction is the release of Cathepsin

G by neutrophil degranulation. It has been demonstrated recently that aprotinin can significantly inhibit the platelet activation due to purified Cathepsin G, this mechanism forming a direct inhibition of inappropriate neutrophil mediated platelet activation.

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