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

The effects of argatroban, a direct thrombin inhibitor, on the Internationa l Normalized Ratio (INR), activated partial thromboplastin time (aPTT) and functional factor X during warfarin co-administration were established to p rovide means to interpret INRs during argatroban/warfarin co-therapy. Twent y-four subjects receiving warfarin (7.5 mg, day 1; 3-6 mg/day, days 2-10) a nd argalroban (1-4 mug/kg/min over 5 h, days 1-11) were assessed daily far these coagulation parameters prior to argatroban infusion (warfarin "monoth erapy") and at its conclusion ("co-therapy"). Argatroban increased aPTTs do se-dependently. Go-therapy INR increased linearly with monotherapy INR, wit h slope sensitive to argatroban dose and thromboplastin used. Prediction er rors for monotherapy INRs were less than or equal to+/- 0.4 for argatroban 1-2 mug/kg/min but greater than or equal to+/-1.0 for higher doses. Despite co-therapy INRs >7, no major bleeding occurred. Factor X remained greater than or equal to 37% of normal. Therefore, the predictable effect of argatr oban (less than or equal to2 mg/kg/min only) on INRs during warfarin co-the rapy allows for reliable prediction of the level of oral anticoagulation.