Warfarin initiation and monitoring with clotting factors II, VII, and X

Abstract

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.