Determination of the sample size (INR 4.5 to 10.0): The estimated rate of all bleeding in patients who present with excessive, warfarin-associated prolongation of the INR, treated with simple warfarin withdrawal, is 8% over the ensuing 30 days (8). We believe that clinicians would be willing to treat a minimum of 20 patients with oral vitamin K to prevent one episode of bleeding, thus the "minimally clinically important difference" that we wish to reliably detect is 5% (21;22). This reduction in the risk of bleeding (from 8% in those who receive placebo to 3% in those who receive vitamin K) represents about a 60% risk reduction. It is reasonable to expect that 1.25 mg of oral vitamin K will produce at least a 60% reduction in the risk of bleeding based on the following assumptions: (a) The INR in the placebo arm is likely to decline by about one INR point over the first 24 hours while the INR in the vitamin K group is likely to decline by about 3.9 INR points. These declines are based on the results achieved in our 3 published studies of oral vitamin K (10;12;13). (b) A 2.9 point reduction in the INR should be associated with a 6 fold reduction in the risk of hemorrhage (based on the assumption that a 1 point increase in the INR doubles the risk of bleeding (4-7)). (c) The 60 percent risk reduction is a conservative interpretation of the effect of a 6 fold decrease in the risk of hemorrhage.