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Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report
BACKGROUND: Warfarin is the most widely used oral anticoagulant; nevertheless, dosing of warfarin is problematic for clinicians worldwide. Inter-individual variability in response to warfarin is attributed to genetic as well as non-genetic factors. Pharmacogenomics studies have identified variants i...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608913/ https://www.ncbi.nlm.nih.gov/pubmed/36303140 http://dx.doi.org/10.1186/s12959-022-00425-8 |
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author | Aldiban, Weam Altawil, Yara Hussein, Samir Aljamali, Majd Youssef, Lama A. |
author_facet | Aldiban, Weam Altawil, Yara Hussein, Samir Aljamali, Majd Youssef, Lama A. |
author_sort | Aldiban, Weam |
collection | PubMed |
description | BACKGROUND: Warfarin is the most widely used oral anticoagulant; nevertheless, dosing of warfarin is problematic for clinicians worldwide. Inter-individual variability in response to warfarin is attributed to genetic as well as non-genetic factors. Pharmacogenomics studies have identified variants in CYP2C9 and VKORC1 genes as significant predictors of warfarin dose, however, phenotypes of rare variants are not well characterized. CASE PRESENTATION: We report a case of hyper-responsiveness to warfarin in a 22-year-old outpatient with Crohn's disease who presented with a swollen, red, and painful left calf. Deep venous thrombosis (DVT) in the left lower extremity was confirmed via ultrasonography, and hence, anticoagulation therapy of heparin and concomitant warfarin was initiated. Warfarin dose of 7.5 mg/day was estimated by the physician based on clinical factors. Higher than the expected international normalized ratio (INR) value of 4.5 necessitated the reduction of the warfarin dose to 5 and eventually to 2.5 mg/day to reach a therapeutic INR value of 2.6. Pharmacogenetic profiling of the VKORC1 -1639G > A and CYP2C9 *2, *3, *4, *5, *8, *14, *20, *24, *26, *33, *40, *41, *42, *43, *45, *46, *55, *62, *63, *66, *68, *72, *73 and *78 revealed a VKORC1-1639GA/CYP2C9*1*46 genotype. The lower catalytic activity of the CYP2C9*46 (A149T) variant was previously reported in in vitro settings. CONCLUSIONS: This is the first report on a case of warfarin hyper-responsive phenotype of a patient with the heterozygous CYP2C9*1*46 polymorphism. |
format | Online Article Text |
id | pubmed-9608913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-96089132022-10-28 Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report Aldiban, Weam Altawil, Yara Hussein, Samir Aljamali, Majd Youssef, Lama A. Thromb J Case Report BACKGROUND: Warfarin is the most widely used oral anticoagulant; nevertheless, dosing of warfarin is problematic for clinicians worldwide. Inter-individual variability in response to warfarin is attributed to genetic as well as non-genetic factors. Pharmacogenomics studies have identified variants in CYP2C9 and VKORC1 genes as significant predictors of warfarin dose, however, phenotypes of rare variants are not well characterized. CASE PRESENTATION: We report a case of hyper-responsiveness to warfarin in a 22-year-old outpatient with Crohn's disease who presented with a swollen, red, and painful left calf. Deep venous thrombosis (DVT) in the left lower extremity was confirmed via ultrasonography, and hence, anticoagulation therapy of heparin and concomitant warfarin was initiated. Warfarin dose of 7.5 mg/day was estimated by the physician based on clinical factors. Higher than the expected international normalized ratio (INR) value of 4.5 necessitated the reduction of the warfarin dose to 5 and eventually to 2.5 mg/day to reach a therapeutic INR value of 2.6. Pharmacogenetic profiling of the VKORC1 -1639G > A and CYP2C9 *2, *3, *4, *5, *8, *14, *20, *24, *26, *33, *40, *41, *42, *43, *45, *46, *55, *62, *63, *66, *68, *72, *73 and *78 revealed a VKORC1-1639GA/CYP2C9*1*46 genotype. The lower catalytic activity of the CYP2C9*46 (A149T) variant was previously reported in in vitro settings. CONCLUSIONS: This is the first report on a case of warfarin hyper-responsive phenotype of a patient with the heterozygous CYP2C9*1*46 polymorphism. BioMed Central 2022-10-27 /pmc/articles/PMC9608913/ /pubmed/36303140 http://dx.doi.org/10.1186/s12959-022-00425-8 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Case Report Aldiban, Weam Altawil, Yara Hussein, Samir Aljamali, Majd Youssef, Lama A. Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report |
title | Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report |
title_full | Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report |
title_fullStr | Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report |
title_full_unstemmed | Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report |
title_short | Hyper-responsiveness to warfarin in a young patient with the VKORC1 -1639GA/CYP2C9*1*46 genotype: a case report |
title_sort | hyper-responsiveness to warfarin in a young patient with the vkorc1 -1639ga/cyp2c9*1*46 genotype: a case report |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9608913/ https://www.ncbi.nlm.nih.gov/pubmed/36303140 http://dx.doi.org/10.1186/s12959-022-00425-8 |
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