Abstract

Clinical case of a 10-year-old patient, diagnosed with dilated cardiomyopathy, who upon receiving standard doses of acenocoumarol reaches INR values greater than 10 and others reported as uncoagulable, forcing treatment to be suspended and restarted on more than once. Expected and stable INR levels are achieved after more than 30 days of treatment, unexpectedly with half the recommended dose for a patient her age. We decided to carry out a pharmacogenomic study that included nucleotide genetic polymorphisms (SNPs) with different degrees of association with dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853 and rs1057910 (CYP2C9 gene), by RT-PCR technology TaqMan®, for a retrospective analysis case. The patient resulted to be homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2). National and international evidence shows that this genetic profile is strongly associated with AVK lower doses requirement retrospective. In conclusion, this pharmacogenetic analysis confirms that the condition of the patient, with low expression of the therapeutic target of the VKA (Vitamin K epoxide reductase), made the requirement of a lower predictable dose than established according to clinical protocols and literature, as it has been recommended by FDA and the PharmGKB® for coumarin drugs. The a priori genotypic analysis of the patient would have allowed to reach the therapeutic range in shorter times than those observed, avoiding potential risks of bleeding. This finding demonstrates the importance of the pharmacogenetic analysis in treatments with high variability and a narrow therapeutic range drugs.