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

S.B. Sheth; R.A. DiCicco; M.J. Hursting; T. Montague; D.K. Jorkasky

doi:10.1055/s-0037-1615601

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(03): 435-440
DOI: 10.1055/s-0037-1615601

Review Article

Schattauer GmbH

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

S.B. Sheth

¹SmithKline Beecham Pharmaceuticals, Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, PA, and Texas Biotechnology Corporation (as consultant), Houston, TX, USA

,

R.A. DiCicco

¹SmithKline Beecham Pharmaceuticals, Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, PA, and Texas Biotechnology Corporation (as consultant), Houston, TX, USA

,

M.J. Hursting

¹SmithKline Beecham Pharmaceuticals, Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, PA, and Texas Biotechnology Corporation (as consultant), Houston, TX, USA

,

T. Montague

¹SmithKline Beecham Pharmaceuticals, Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, PA, and Texas Biotechnology Corporation (as consultant), Houston, TX, USA

,

D.K. Jorkasky

¹SmithKline Beecham Pharmaceuticals, Presbyterian Medical Center, University of Pennsylvania Health System, Philadelphia, PA, and Texas Biotechnology Corporation (as consultant), Houston, TX, USA

› Author Affiliations

Abstract

Summary

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 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.

Keywords

Argatroban - warfarin - direct thrombin inhibitors - International Normalized Ratio

Full Text

References

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