Oral anticoagulant use continues to increase rapidly. In this setting, it is important to recognise that some normal individuals can demonstrate resistance to anticoagulation with warfarin. Such patients require high daily doses of warfarin (>20 mg) in order to maintain an international normalised ratio (INR) within the target therapeutic range (2-3). We describe the case of an elderly gentleman with atrial fibrillation who demonstrated true warfarin resistance.Methods
We performed vitamin K epoxide reductase subunit 1 (VKORC1) gene coding sequence analysis using polymerase chain reaction primers.Results
We demonstrated that our patient was heterozygous for a 383 T→G transition in exon 2 of the VKORC1 gene.Conclusions
This is the first documented Irish case of true warfarin resistance as a result of a mutation in VKORC1, a novel gene encoding a component of the epoxide reductase enzyme complex which is an essential component in the recycling pathway of vitamin K and is postulated to be one of the sites of action of warfarin.