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[Profibrinolytic activity of recombinant hirudin?]
D A Tsakiris1, D Meyer, J Fabbri
1Gerinnungs- und Fibrinolyselaboratorium, Kantonsspital Basel.
Abstract:
Recombinant hirudin (rH, CGP 39393) is a potent thrombin inhibitor. In addition to its anticoagulant effect, we investigated its profibrinolytic activity in vitro and ex vivo. The fibrinolytic activity of the euglobulin fraction of 15 normal plasmas with or without urokinase was tested in a fibrin plate assay both before and after addition of rH. The same cycle was repeated in 8 plasmas with heparin instead of rH. For the ex vivo evaluation 12 healthy volunteers received 0.1-0.3 mg/kg/h rH for 6 h. Blood samples were drawn at 0 h, 6 h, 12 h and 24 h and various fibrinolytic parameters were assayed. In the presence of rH or heparin a slightly stronger fibrinolytic effect was observed, measured as fibrin plate lysis activity, both when rH was added to plasma in vitro and when it was administered intravenously. However, this may be explained by the specific anticoagulant action of rH and heparin in the dynamic equilibrium of fibrinolysis and clotting in the test system. Moreover, under rH treatment the observed changes in the various fibrinolytic parameters could not be differentiated from the normal circadian rhythm of these proteins. There was no convincing evidence to indicate enhancement of plasma fibrinolytic activity by recombinant hirudin.