The Second Reported Kindred with Hereditary Resistance to Oral Anticoagulant Drugs

Abstract

In this second reported kindred of hereditary resistance to oral anticoagulant drugs the propositus required 75 to 80 mg of sodium warfarin a day (25 standard deviations above the average dose) to achieve hypoprothrombinemia in the therapeutic range. With this dose, the hypoprothrombinemia could be corrected with daily doses of vitamin K1 of as little as 0.125 mg. Seventeen other family members had an equally resistant response to the oral anticoagulant drugs. The metabolism of sodium warfarin and the vitamin-K-dependent clotting factors were entirely normal. The pharmacologic mechanism for the resistance is a mutation of the receptor site for vitamin K and oral anticoagulants. The genetic data for the resistant response in both human kindreds indicate the dominant expression of a single gene located on an autosomal chromosome.