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August 20, 1997

Loading Dose and Monitoring of Warfarin Therapy

Author Affiliations

Washington, DC

JAMA. 1997;278(7):548. doi:10.1001/jama.1997.03550070040028

To the Editor.  —In the Questions and Answers on loading dose of warfarin, Dr Lamb1 correctly advises against the loading dose since it is clinically unwarranted and potentially hazardous because of increased risk of hemorrhage. This recommendation is consistent with the current scientific data. The literature also supports the author's second recommendation to initiate monitoring using the international normalized ratio (INR) and to institute daily adjustment of warfarin dosage immediately after the therapy is begun. However, the latter recommendation appears to conflict with the pharmocodynamics of warfarin therapy, which was briefly but well described by the author.During the first 72 to 96 hours after initiation of warfarin therapy, INR reflects the suppression of factor VII (half-life 6 hours) only, but not more important homeostatic factors VI, IX, and X, which have longer half-lives.2 In addition, initiation of warfarin therapy even with a maintenance dose is not completely