International Journal of Medical Research & Health Sciences
  • Year: 2018
  • Volume: 7
  • Issue: 3

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

  • Author:
  • Abdelhak Elkhazraji1,, Sara Rharrit2, Jean Uwingabiye2, Hafid Zahid3, Azeddine Ibrahimi4, Nezha Messaoudi5
  • Total Page Count: 7
  • Page Number: 66 to 72

1PhD Student, Laboratory of Medical Biotechnology (Med Biotech), Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, Morocco

2Resident, Faculty of Medicine and Pharmacy, Laboratory of Hematology and Immuno-Hematology, Mohamed V Military Teaching Hospital, Mohammed V University, Rabat, Morocco

3Professor, Faculty of Medicine and Pharmacy, Laboratory of Hematology and Immuno-Hematology, Mohamed V Military Teaching Hospital, Mohammed V University, Rabat, Morocco

4Professor and Chairman, Laboratory of Medical Biotechnology (Med Biotech), Faculty of Medicine and Pharmacy, Mohamed V University, Rabat, Morocco

5 Professor and Chairman, Faculty of Medicine and Pharmacy, Laboratory of Hematology and Immuno-Hematology, Mohamed V Military Teaching Hospital, Mohammed V University, Rabat, Morocco

*Corresponding e-mail: abdelhak.elkhazraji@yahoo.fr

Online published on 19 November, 2018.

Abstract

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.

Keywords

Hypersensitivity, Acenocoumarol, VKORC1, CYP2C9