Hypersensitivity to Acenocoumarol Revealing a Homozygous Mutation for VKORC1 - 1639 G > A and VKORC1 1173 C > T and Heterozygous for CYP2C9 * 2 and CYP2C9 * 3

The initiation of treatment with acenocoumarol is a critical phase that can lead to an iatrogenic event in some patients carrying polymorphisms of the genes involved in the response to treatment, notably VKORC1 and CYP2C9. We report the first case in Morocco and Africa of hypersensitivity to acenocoumarol at the initiation dose in a 70-year-old patient who required an extremely low maintenance dose (0.25 mg / day) to achieve INR target. Genotyping results showed that the patient was homozygous mutated for (VKORC1) -1639 G> A and (VKORC1) -11173 C> T and heterozygous for (CYP2C9) * 2 and (CYP2C9) * 3 demonstrating extreme sensitivity to acenocoumarol due to the cumulative effect of these genetic polymorphisms on the maintenance dose of the anticoagulant. Our study shows the major benefit of prospective genotyping of CYP2C9 and VKORC1 prior to initiation of acenocoumarol treatment, as a good predictor of extreme susceptibility to VKA.