• Karen T Schultz and Tammy J Bungard.
• Anticoagulation Management Service, University of Alberta Hospital, Alberta Health Services, Edmonton, Canada.
• Pharmacotherapy. 2011 Aug 1; 31 (8): 793-805.

Study ObjectivesTo determine dosing options for decreasing the time to achieve a therapeutic international normalized ratio (INR) threshold of 2.0 when restarting warfarin in an ambulatory population whose previous warfarin maintenance doses are known, and to identify thromboembolic and major bleeding events up to 90 days after disruption of warfarin therapy.DesignRetrospective medical record review.SettingAmbulatory anticoagulation management service (AMS) in Canada.PatientsThirty-six patients managed by the AMS whose warfarin doses were withheld for a minimum of 4 consecutive days, who did not use vitamin K for warfarin reversal, and who had at least 90 days of follow-up after restarting warfarin between January 1, 2005, and April 1, 2010.Measurements And Main ResultsForty-one episodes of warfarin reinitiation in the 36 patients were identified. Time to therapeutic INR was defined as days to reach a therapeutic INR threshold of 2.0, regardless of usual target INR or indication for warfarin therapy. Restarting warfarin at previous maintenance doses (i.e., no loading dose) took a median of 20.5 days (interquartile range [IQR] 14.3-31.3 days) to achieve a therapeutic INR. In contrast, administering a loading dose approximating 40% more than the previous daily maintenance dose for 2 or 3 days, on either the first day or after the first day of warfarin reinitiation, shortened the time to achieve a therapeutic INR to a median of 5.0 days (IQR 4.0-6.0 days) or 6.0 days (IQR 5.0-7.8 days), respectively. No thromboembolic events occurred during the 90-day follow-up period. Six episodes of major bleeding occurred. All occurred in patients who received a warfarin loading dose; however, most had INRs less than 2.0 and had risk factors for bleeding.ConclusionIn select patients, the option of administering a warfarin loading dose of approximately 40% greater than the previous daily maintenance dose for 2 or 3 days shortens the time to achieving therapeutic anticoagulation.

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