Genetic Warfarin-Resistance Resulting in Surgery to Change a Prosthetic Valve

Warfarin is a readily available anticoagulant used worldwide in a variety of clinical scenarios. Patients who need more than 15 mg/day are considered to be warfarin resistant. Numerous genes have been implicated in warfarin pharmacogenetics, with genes encoding CYP2C9 and VKORC1 shown to be the most important determinants of drug dosage requirements. A 27-year-old woman was admitted as she had a sub-therapeutic international normalized ratio (INR) after prosthetic mitral valve replacement. Even after a warfarin dose of 50 mg/day, her INR was not in the therapeutic range, so the heart team decided to replace her metallic valve with a bioprosthetic valve, thus alleviating the need for anticoagulation.

Genetic warfarin resistance is rare and mainly associated with two genes encoding CYP2C9 and VKORC1.In addition to dietary counselling and drug compliance, options in warfarin-resistant patients include increasing the warfarin dose, which carries a risk of bleeding complications, or switching to novel oral anticoagulants, which increases the risk of prosthetic valve thrombosis.We replaced a metallic valve with a bioprosthetic valve, which is the first time this has been documented in a patient with warfarin resistance.