COMPARISON OF 5-MG AND 10-MG LOADING DOSES IN INITIATION OF WARFARIN THERAPY

Background: Loading doses of warfarin that are larger than those used for maintenance therapy are widely used in clinical practice, but they have never been prospectively evaluated. Objective: To compare the ef fect of 5- to 10-mg loading doses of warfarin on laboratory markers of warfarin's anticoagulant effect. Design: Randomized clinical trial. S etting: Tertiary care teaching hospital. Patients: 49 patients seen ov er a 5-month period with a target international normalized ratio (INR) of 2.0 to 3.0. Intervention: Patients were randomly assigned to recei ve an initial dose of 5 or 10 mg of warfarin. Subsequent doses of warf arin were administered on the basis of dosing monograms. Measurements: INRs and levels of factor II, VII, IX, and X and protein C were measu red daily for 5 days. Results: 11 of 25 patients in the 10-mg group (4 4% [95% CI, 34% to 54%]) and 2 of 24 patients in the 5-mg group (8% [C I, 3% to 14%]) had INRs greater than 2.0 at 36 hours (P = 0.005), at w hich time the factor VII levels were 27% (CI, 18% to 36%) in the 10-mg group and 54% (CI, 43% to 65%) in the 5-mg group (P < 0.001). In cont rast, factor II levels were 74% (CI, 67% to 81%) in the 10-mg group an d 82% (CI, 73% to 93%) in the 5-mg group (P > 0.2). At 60 hours, 9 of 25 patients in the 10-mg group (36% [CI, 17% to 54%]) and no patients in the 5-mg group had INRs greater than 3.0. At 84 hours, 15 of 24 pat ients in the 10-mg group (63% [CI, 43% to 81%]) and 19 of 24 patients in the 5-mg group (79% [CI, 62% to 95%]) had INRs between 2.0 and 3.0. Four patients in the 10-mg group and 1 patient in the 5-mg group rece ived vitamin K for excessive prolongation of the INR. Conclusions: A 5 -mg loading dose of warfarin produces less excess anticoagulation than does a 10-mg loading dose; the smaller dose also avoids the developme nt of a potential hypercoagulable state caused by precipitous decrease s in levels of protein C during the first 36 hours of warfarin therapy .