We read with interest the report by Harrison and colleagues [1]. The authors measured the early changes in clotting factor levels in patients given a 10-mg warfarin loading dose compared with changes in patients receiving a 5-mg dose. Another important clinical end point is the time it takes for a patient to achieve a stable therapeutic warfarin dose. This can be defined as the number of days after initiation of warfarin therapy until the patient attains two consecutive INRs in the desired therapeutic range [2], measured at least 72 hours apart. In a prospective study of a standard protocol of consecutive patients beginning warfarin therapy, we compared 23 patients who began receiving 10 mg with 19 patients who began receiving 7.5 mg or less as the initial dose. Warfarin dosing and follow-up were left to the discretion of experienced anticoagulation practitioners. Patients receiving a 10-mg loading dose took almost three times longer to reach a stable therapeutic dose (45 days compared with 16 days; P = 0.005). In addition, patients who received the higher loading dose were three times more likely to have an INR exceeding 4.0 than were patients who received the lower loading doses (13 instances compared with 4). More laboratory tests and dose adjustments were required in the patients receiving the higher loading dose.

Initiation of warfarin therapy with estimated maintenance doses seems to reduce periods of fluctuating anticoagulation as well as potential transient hypercoagulable states associated with warfarin necrosis. Avoiding large traditional loading doses may also result in faster attainment of a stable, therapeutically anticoagulated state in clinical practice and may be less costly. With warfarin, less may be better in the short and long runs.