14
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Análisis farmacogenético retrospectivo de una paciente pediátrica en tratamiento anticoagulante: caso clínico Translated title: Retrospective pharmacogenetic analysis of a pediatric patient under anticoagulant treatment: Clinical case

      case-report

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Resumen

          Se presenta el caso clínico de una paciente de 10 años diagnosticada con miocardiopatía dilatada, quien registró valores en el índice internacional normalizado (International Normalized Ratio, INR) superiores a 10 con la dosis estándar de acenocumarol, además de otros valores que indicaban el estado incoagulable, lo que obligó a suspender y reiniciar el tratamiento en varias ocasiones. Después de más de 30 días de tratamiento, sorprendentemente se lograron los niveles esperados y estables en el INR con la mitad de la dosis recomendada para una paciente de su edad y peso.

          Se decidió hacer un análisis farmacogenético retrospectivo del caso mediante RT-PCR con sondas TaqMan™ que incluyó cinco polimorfismos de un solo nucleótido y distinto grado de asociación con la dosis-respuesta a los fármacos antivitamínicos K (AVK): rs2108622 (gen CYP4F2), rs9923231, rs7294 (gen VKORC1), rs1799853 y rs1057910 (gen CYP2C9). La paciente resultó ser homocigota para el rs9923231 (VKORC1) y heterocigota para el rs2108622 (CYP4F2). Se ha evidenciado a nivel nacional e internacional que este perfil genético está fuertemente asociado con una necesidad de dosis menores de antivitamínicos K.

          En conclusión, el análisis farmacogenético confirmó que la condición genética de la paciente, la cual conlleva una baja expresión de la enzima VKORC1 (blanco terapéutico de los antivitamínicos K), hacía predecible la necesidad de una dosis menor a la establecida según los protocolos clínicos recomendados por la Food and Drug Administration (FDA) y PharmGKB™ para los fármacos cumarínicos. El análisis genotípico previo de la paciente hubiese permitido alcanzar el rango terapéutico más prontamente, evitando potenciales riesgos de hemorragia, lo que demuestra la importancia de los análisis farmacogenéticos en tratamientos de gran variabilidad y estrecho rango terapéutico.

          Abstract

          We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan ® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2), a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence.

          In conclusion, the pharmacogenetic analysis confirmed that this patient's genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB ® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.

          Related collections

          Most cited references16

          • Record: found
          • Abstract: found
          • Article: not found

          Pharmacogenomics knowledge for personalized medicine.

          The Pharmacogenomics Knowledgebase (PharmGKB) is a resource that collects, curates, and disseminates information about the impact of human genetic variation on drug responses. It provides clinically relevant information, including dosing guidelines, annotated drug labels, and potentially actionable gene-drug associations and genotype-phenotype relationships. Curators assign levels of evidence to variant-drug associations using well-defined criteria based on careful literature review. Thus, PharmGKB is a useful source of high-quality information supporting personalized medicine-implementation projects.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Pharmacogenetics-Guided Warfarin Dosing: 2017 Update.

            This document is an update to the 2011 Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2C9 and VKORC1 genotypes and warfarin dosing. Evidence from the published literature is presented for CYP2C9, VKORC1, CYP4F2, and rs12777823 genotype-guided warfarin dosing to achieve a target international normalized ratio of 2-3 when clinical genotype results are available. In addition, this updated guideline incorporates recommendations for adult and pediatric patients that are specific to continental ancestry.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Evidence-based management of anticoagulant therapy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

              High-quality anticoagulation management is required to keep these narrow therapeutic index medications as effective and safe as possible. This article focuses on the common important management questions for which, at a minimum, low-quality published evidence is available to guide best practices. The methods of this guideline follow those described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. Most practical clinical questions regarding the management of anticoagulation, both oral and parenteral, have not been adequately addressed by randomized trials. We found sufficient evidence for summaries of recommendations for 23 questions, of which only two are strong rather than weak recommendations. Strong recommendations include targeting an international normalized ratio of 2.0 to 3.0 for patients on vitamin K antagonist therapy (Grade 1B) and not routinely using pharmacogenetic testing for guiding doses of vitamin K antagonist (Grade 1B). Weak recommendations deal with such issues as loading doses, initiation overlap, monitoring frequency, vitamin K supplementation, patient self-management, weight and renal function adjustment of doses, dosing decision support, drug interactions to avoid, and prevention and management of bleeding complications. We also address anticoagulation management services and intensive patient education. We offer guidance for many common anticoagulation-related management problems. Most anticoagulation management questions have not been adequately studied.
                Bookmark

                Author and article information

                Journal
                Biomedica
                Biomedica
                bio
                Biomédica
                Instituto Nacional de Salud
                0120-4157
                2590-7379
                22 September 2021
                September 2021
                : 41
                : 3
                : 5840-6408
                Affiliations
                [1 ] original Laboratorio Clínico, Hospital Dr. Luis Calvo Mackenna, Santiago, Chile orgnameLaboratorio Clínico, Hospital Dr. Luis Calvo Mackenna Santiago, Chile
                [2 ] original Laboratorio de Carcinogénesis Química y Farmacogenética, Departamento de Oncología Básico-Clínico, Facultad de Medicina, Universidad de Chile, Santiago, Chile normalizedUniversidad de Chile orgdiv2Departamento de Oncología Básico-Clínico orgdiv1Facultad de Medicina orgnameUniversidad de Chile Santiago, Chile
                [3 ] original Servicio de Farmacia, Hospital Clínico Red de Salud UC-Christus, Santiago, Chile orgnameHospital Clínico Red de Salud UC-Christus Santiago, Chile
                [4 ] original Red Latinoamericana para la Implementación y Validación de Guías Clínicas Farmacogenómicas (RELIVAF-CYTED), Santiago, Chile orgnameRed Latinoamericana para la Implementación y Validación de Guías Clínicas Farmacogenómicas (RELIVAF-CYTED) Santiago, Chile
                Author notes
                [* ] Correspondencia: Nelson Miguel Varela, Departamento de Oncología Básico-Clínico, Facultad de Medicina, Universidad de Chile, Carlos Schachtebeck 299, Quinta Normal, Santiago, Chile Teléfono: (562) 2977 0743; móvil: (969) 8500 1351 nvarela@ 123456med.uchile.cl

                Conflicto de intereses: Los autores declaran no tener ningún conflicto de intereses.

                Article
                10.7705/biomedica.5840
                8519589
                34559488
                473f8daf-9b3d-426f-9f9a-7d3c1e0805fa

                Este es un artículo publicado en acceso abierto bajo una licencia Creative Commons

                History
                : 06 October 2020
                : 28 May 2021
                : 15 June 2021
                Page count
                Figures: 1, Tables: 2, Equations: 0, References: 14, Pages: 6
                Categories
                Reporte De Caso

                acenocumarol,farmacogenética,anticoagulantes,vitamina k,acenocoumarol,pharmacogenetics,anticoagulants,vitamin k

                Comments

                Comment on this article