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Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management

BACKGROUND: Annually, 10% of warfarin patients will likely need to stop warfarin prior to elective surgery to achieve a baseline international normalization ratio (INR) level (INR ≤ 1.2) at the time of the procedure. This study explores the influence of genetic and non-genetic factors on INR normali...

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Autores principales: Eljilany, Islam, Elarref, Mohamed, Shallik, Nabil, Elzouki, Abdel-Naser, Bader, Loulia, El-Bardissy, Ahmed, Abdelsamad, Osama, Al-Badriyeh, Daoud, Cavallari, Larisa H, Elewa, Hazem
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409603/
https://www.ncbi.nlm.nih.gov/pubmed/34483679
http://dx.doi.org/10.2147/PGPM.S322743
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author Eljilany, Islam
Elarref, Mohamed
Shallik, Nabil
Elzouki, Abdel-Naser
Bader, Loulia
El-Bardissy, Ahmed
Abdelsamad, Osama
Al-Badriyeh, Daoud
Cavallari, Larisa H
Elewa, Hazem
author_facet Eljilany, Islam
Elarref, Mohamed
Shallik, Nabil
Elzouki, Abdel-Naser
Bader, Loulia
El-Bardissy, Ahmed
Abdelsamad, Osama
Al-Badriyeh, Daoud
Cavallari, Larisa H
Elewa, Hazem
author_sort Eljilany, Islam
collection PubMed
description BACKGROUND: Annually, 10% of warfarin patients will likely need to stop warfarin prior to elective surgery to achieve a baseline international normalization ratio (INR) level (INR ≤ 1.2) at the time of the procedure. This study explores the influence of genetic and non-genetic factors on INR normalization in the Arab (major part of Near Eastern) population in preprocedural warfarin management. METHODS: An observational prospective cohort study was designed to recruit Arab patients taking warfarin and scheduled for an elective procedure. Two INR readings were recorded. DNA extraction and genotyping of variants in CYP2C9*2, CYP2C9*3, CYP4F2*3, VKORC1*2, and FII (rs5896) and FVII (rs3093229) genes using real-time polymerase chain reaction were performed. RESULTS: Data from 116 patients were included in the analysis. CYP2C9 and VKORC1 genetic variants carriers required lower maintenance dose compared to non-carriers. The analysis showed that ciprofloxacin, antiplatelet medications, and INR index (INR at visit 1) are the only factors associated with the INR decline rate. Also, the proportion of CYP2C9*3 carriers with normal INR (≤1.2) on the day of surgery was significantly lower than those with wild-type genotype (28% vs 60%, p=0.013). In addition, heparin bridging, INR target, and Sudanese nationality are significant predictors of INR normalization (≤1.2) on the day of the procedure. CONCLUSION: Despite the confirmed effect of genetic factors on warfarin maintenance dose, the study was not able to find a significant effect of any genetic factor on the rate of INR normalization possibly due to the small sample size. Index INR and interacting medications showed to be significant predictors of INR decline rate.
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spelling pubmed-84096032021-09-02 Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management Eljilany, Islam Elarref, Mohamed Shallik, Nabil Elzouki, Abdel-Naser Bader, Loulia El-Bardissy, Ahmed Abdelsamad, Osama Al-Badriyeh, Daoud Cavallari, Larisa H Elewa, Hazem Pharmgenomics Pers Med Original Research BACKGROUND: Annually, 10% of warfarin patients will likely need to stop warfarin prior to elective surgery to achieve a baseline international normalization ratio (INR) level (INR ≤ 1.2) at the time of the procedure. This study explores the influence of genetic and non-genetic factors on INR normalization in the Arab (major part of Near Eastern) population in preprocedural warfarin management. METHODS: An observational prospective cohort study was designed to recruit Arab patients taking warfarin and scheduled for an elective procedure. Two INR readings were recorded. DNA extraction and genotyping of variants in CYP2C9*2, CYP2C9*3, CYP4F2*3, VKORC1*2, and FII (rs5896) and FVII (rs3093229) genes using real-time polymerase chain reaction were performed. RESULTS: Data from 116 patients were included in the analysis. CYP2C9 and VKORC1 genetic variants carriers required lower maintenance dose compared to non-carriers. The analysis showed that ciprofloxacin, antiplatelet medications, and INR index (INR at visit 1) are the only factors associated with the INR decline rate. Also, the proportion of CYP2C9*3 carriers with normal INR (≤1.2) on the day of surgery was significantly lower than those with wild-type genotype (28% vs 60%, p=0.013). In addition, heparin bridging, INR target, and Sudanese nationality are significant predictors of INR normalization (≤1.2) on the day of the procedure. CONCLUSION: Despite the confirmed effect of genetic factors on warfarin maintenance dose, the study was not able to find a significant effect of any genetic factor on the rate of INR normalization possibly due to the small sample size. Index INR and interacting medications showed to be significant predictors of INR decline rate. Dove 2021-08-28 /pmc/articles/PMC8409603/ /pubmed/34483679 http://dx.doi.org/10.2147/PGPM.S322743 Text en © 2021 Eljilany et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Eljilany, Islam
Elarref, Mohamed
Shallik, Nabil
Elzouki, Abdel-Naser
Bader, Loulia
El-Bardissy, Ahmed
Abdelsamad, Osama
Al-Badriyeh, Daoud
Cavallari, Larisa H
Elewa, Hazem
Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management
title Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management
title_full Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management
title_fullStr Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management
title_full_unstemmed Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management
title_short Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management
title_sort genetic and non-genetic factors impact on inr normalization in preprocedural warfarin management
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409603/
https://www.ncbi.nlm.nih.gov/pubmed/34483679
http://dx.doi.org/10.2147/PGPM.S322743
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