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Warfarin Initiation and Monitoring with Clotting Factors II, VII, and X

at time of writing, Pharmacy Practice Resident, Department of Pharmacy, University of California Davis Medical Center, Sacramento, CA; now, Clinical Pharmacist, Department of Pharmaceutical Services, University of California Davis Medical Center; Assistant Clinical Professor of Pharmacy, School of Pharmacy, University of California at San Francisco, San Francisco, CA

Robert C Gosselin, CLS

Coagulation Specialist, Department of Laboratory Services, University of California Davis Medical Center

Jaime A Diaz, MD

Resident, Department of Emergency Medicine, University of California Davis Medical Center

William E Dager, PharmD FCSHP

Pharmacist Specialist, Department of Pharmaceutical Services, University of California Davis Medical Center; Clinical Professor of Pharmacy, School of Pharmacy, University of California at San Francisco; Associate Clinical Professor of Medicine, School of Medicine, University of California Davis

Reprints: William E Dager PharmD FCSHP, University of California Davis Medical Center, 2315 Stockton Blvd., Sacramento, CA 95817-2201, fax 916/703-4031, william.dager{at}ucdmc.ucdavis.edu

OBJECTIVE: To report a case of a patient with antiphospholipid antibody syndrome and multiple thromboses who developed heparin-induced thrombocytopenia (HIT) and subsequent international normalized ratio (INR) prolongation possibly due to antiphospholipid antibodies.

CASE SUMMARY: A 56-year-old white woman with a history of antiphospholipid antibody syndrome and thrombosis taking chronic warfarin was admitted for gastrointestinal concerns and found to have an INR >14. Warfarin was discontinued, vitamin K was administered, and a heparin infusion was initiated. Over the next 2 days, thrombocytopenia, hypotension, tachycardia, hyponatremia, and progressive abdominal pain developed. Upon transfer to a tertiary care center, HIT was diagnosed, and a lepirudin infusion was initiated. Subsequently, a sudden elevation of the INR occurred (>14) with low prothrombin (factor II) activity. After INR values declined to 2-3, warfarin was reinitiated with dosing adjusted using factor X and II activity levels. Clotting factors II and X activities were measured to monitor long-term warfarin therapy, with no evidence of complications after 7 months.

DISCUSSION: Typically, the INR is used to assess the intensity of anticoagulation. The INR value represents the reduction of clotting factors II, VII, and X. In rare circumstances, an independent inhibitor or interfering substance can interfere with the process of measuring the INR. In such situations, an alternative approach can be direct measurement of clotting factor concentrations.

CONCLUSIONS: Factor II and/or factor X activity levels provided an alternative means for measuring the anticoagulant effects of warfarin in the presence of a significant inhibitor (antiphospholipid antibodies) that biased the INR measurements.

Key Words: factor II, factor VII, factor X, heparin-induced thrombocytopenia, international normalized ratio, lepirudin, monitoring, warfarin

Published Online, December 30, 2003. www.theannals.com, DOI 10.1345/aph.1D266