ECARIN CLOTTING TIME - A PREDICTIVE COAGULATION ASSAY FOR THE ANTITHROMBOTIC ACTIVITY OF ARGATROBAN IN THE RAT

We studied the use of the Ecarin Clotting Time (ECT) as a predictive a ssay of the antithrombotic effects of argatroban in a new tissue facto r-dependent model of venous thrombosis and a model of arterial thrombo sis in the rat. Heparin was used as a reference anticoagulant. Infusio ns of argatroban dose-dependently increased the ECT across the range o f doses required for antithrombotic activity in models of venous and a rterial thrombosis (1.25-40 mu g/kg/min). The TT was only useful as a marker in the case of venous thrombosis, since, in the arterial thromb osis model, the clotting times were >200 s in the majority of animals receiving antithrombotic doses. The aPTT is not sufficiently sensitive to be predictive of an antithrombotic effect in the venous model, and shows only modest increases in the arterial thrombosis model. Heparin did not significantly increase the ECT at and thrombotic doses in the venous thrombosis model. and only increased the ECT by 53% at 40 mu g /kg/min in the arterial model, despite a marked antithrombotic effect. Both the TT and aPTT were dose-dependently increased by heparin at do ses active in the venous model, whereas both parameters were >200 s at doses active in the arterial thrombosis model. Thus, the ECT provides a predictive marker for the antithrombotic activity of argatroban in both venous and arterial thrombosis, at least in the rat.