Interpreting the International Normalized Ratio (INR) in Individuals Receiving Argatroban and Warfarin

Abstract

SummaryThe 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 μg/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 ≤± 0.4 for argatroban 1-2 μg/kg/min but ≥± 1.0 for higher doses. Despite co-therapy INRs >7, no major bleeding occurred. Factor X remained ≥37% of normal. Therefore, the predictable effect of argatroban (≤ 2 mg/kg/min only) on INRs during warfarin co-therapy allows for reliable prediction of the level of oral anticoagulation.