Interpreting the International Normalized Ratio (INR) in individuals receiving argatroban and warfarin

The effects of argatroban, a direct thrombin inhibitor, on the International Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and functional factor X during warfarin co-administration were established to provide means to interpret INRs during argatroban/warfarin co-therapy. Twenty-four subjects receiving warfarin (7.5 mg, day 1; 3-6 mg/day, days 2-10) and argatroban (1-4 microg/kg/min over 5 h, days 1-11) were assessed daily for these coagulation parameters prior to argatroban infusion (warfarin "monotherapy") and at its conclusion ("co-therapy"). Argatroban increased aPTTs dose-dependently. Co-therapy INR increased linearly with monotherapy INR, with slope sensitive to argatroban dose and thromboplastin used. Prediction errors for monotherapy INRs were < or =+/- 0.4 for argatroban 1-2 microg/kg/min but > or = +/-1.0 for higher doses. Despite co-therapy INRs >7, no major bleeding occurred. Factor X remained > or =37% of normal. Therefore, the predictable effect of argatroban (< or =2 microg/kg/min only) [corrected] on INRs during warfarin co-therapy allows for reliable prediction of the level of oral anticoagulation.