Hereditary Warfarin Resistance: Investigation of a Rare Phenomenon

摘要

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 similar relative resistance, confirming that this family is the third to be reported with hereditary resistance to warfarin . The 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. Relative resistance to warfarin can be explained by altered pharmacokinetics of the drug or by a decreased pharmacodynamic effect that occurs in patients who have a high dietary intake of vitamin K or an end-organ resistance to warfarin.