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Pharmaceutical Research

Clinicians can maintain the same warfarin dose in asymptomatic patients with an INR of 3.3 or less without risk of hemorrhage

The anticoagulant warfarin is often used to prevent blood clots in people with a history of thromboembolism. However, the dosage must be monitored closely, often through use of an anticoagulation service (ACS), so that the medication keeps the blood thin enough to prevent clots but not so thin as to cause hemorrhaging.

Because the risk of hemorrhage rises exponentially with rising values of the international normalized ratio (INR), experts agree that the dose of warfarin sodium should be decreased when the INR exceeds 4 but disagree on how to treat an isolated INR of 3-4. According to a recent study that was supported in part by the Agency for Healthcare Research and Quality (HS10133), clinicians can maintain the same warfarin dose in asymptomatic patients with an INR of 3.3 or less (target INR is 2.5) and reduce the dose by 1-20 percent for slightly higher INRs.

Researchers from the Washington University School of Medicine in St. Louis, MO, identified 231 HMO outpatients who were receiving warfarin (half of them for atrial fibrillation, others for venous thromboembolism or other problems) with an INR between 3.2 and 3.4 and no signs of bleeding. Their ACS monitored 103 of the patients; primary care physicians (PCPs) monitored the remaining 128 patients. Except for one patient who developed a nosebleed, none of the 103 ACS patients suffered a major bleed in the 30 days after their mildly elevated INR.

Compared with PCPs, the ACS clinicians were less likely to decrease the dose (22 vs. 47 percent), and when there was a decrease, the ACS clinicians recommended smaller dose reductions. After their elevated INRs, ACS patients had a therapeutic INR sooner than PCP patients (32 vs. 49 days), and ACS patients also had a followup INR test sooner. The median followup INR was 2.7 in 148 patients who maintained their warfarin dose, 2.5 in 77 patients who decreased their dose by 1 to 20 percent, but only 1.7 in 6 patients who decreased their dose by 21 to 43 percent.

For more details, see "Warfarin dose reduction vs. watchful waiting for mild elevations in the international normalized ratio," by Gerald A. Banet, R.N., M.P.H., Amy D. Waterman, Ph.D., Paul E. Milligan, R.Ph., Susan K. Gatchel, C.C.R.C., and Brian F. Gage, M.D., M.Sc., in the February 2003 Chest 123(2), pp. 499-503.

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