Reversal of Warfarin

Abstract

Case Presentation: A 74-year-old woman presents to the emergency department with bruising. She takes warfarin for atrial fibrillation. She has recently begun taking trimethoprim/sulfamethoxazole. Her international normalized ratio (INR) is reported as 8.6. Supratherapeutic INR values are common in warfarin-treated patients. In this case, the antibiotic is the likely cause, but it is not unusual for an INR measurement to exceed 3.0 without explanation. Irrespective of whether a cause for the INR increase can be identified, the patient should be interviewed and examined to ensure she is not bleeding. For an asymptomatic patient whose INR is >5, warfarin should be withheld for at least 1 dose, and close follow-up monitoring should be arranged. This patient's INR will return to the therapeutic range more quickly if she receives low-dose oral vitamin K (as opposed to simple warfarin withdrawal).1 Low-dose oral vitamin K is often considered in such situations because INR elevations like the one described here can be quite alarming to both the patient and the clinician. However, there is uncertainty about the short-term risk of major bleeding in such a patient. In one observational cohort of 1104 warfarin-treated asymptomatic patients with a single INR value between 5.0 and 9.0 (90% of whom were managed with simple warfarin withdrawal), only 0.96% experienced major hemorrhage within 30 days.2 However, an earlier observational study of 114 asymptomatic patients taking warfarin with an INR >6.0 managed without vitamin K reported major bleeding in 5 patients (4.4%; 95% confidence interval, 1.4%–9.9%) during 14 days of follow-up.3 To address this uncertainty, we randomized 355 nonbleeding warfarin-treated patients whose INR was >5.0 and <9.0 to receive either 1.25 mg of oral vitamin K or placebo. Although INR correction was more robust for the vitamin K–treated patients, the rate of major bleeding was low in …