Investigation of a Rare Phenomenon

\s=b\A 57-year-old black woman required a daily dosage of 50 mg of warfarin sodium to maintain her prothrombin time in a therapeutic range. The central volume of distribution and clearance of warfarin were normal for this patient. These findings, combined with the patient's requirement for plasma warfarin levels four times greater than those usually required to achieve adequate anticoagulation, indicated that the relative resistance was due to altered pharmacodynamics of warfarin. The only child of the propositus, a daughter, showed a similar relative resistance, confirming that this family is the third to be reported with hereditary resistance to warfarin. (Arch Intern Med 1985;145:499-501) rPhe anticoagulant warfarin sodium inhibits the vitamin K-dependent carboxylation of the precursors of factors II, VII, IX, and X, thereby preventing the synthesis of factors with normal coagulant activity.1 Relative resistance to warfarin can be explained by altered pharmacokinetics of the drug2·3 or by a decreased pharmacodynamic effect that occurs in patients who have a high dietary intake of vitamin K4 or an "end-organ" resistance to warfarin. This latter phenomenon was described in two kindreds, both of North¬ ern European extraction, by O'Reilly and co-workers5,6 more than ten years ago. lb our knowledge, since the two original papers, no additional kindreds have been reported. We found a normal pharmacokinetic response to warfarin in a black woman who required 50 mg daily to maintain adequate anticoagulation. This finding, combined with a relative resistance to warfarin in her daughter, indicates that this family has an inherited resistance to warfarin that can be explained on a pharmacodynamic basis.