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

• Main Authors: Eljilany I (Author), Elarref M (Author), Shallik N (Author), Elzouki AN (Author), Bader L (Author), El-Bardissy A (Author), Abdelsamad O (Author), Al-Badriyeh D (Author), Cavallari LH (Author), Elewa H (Author)
• Format: Book
• Published: Dove Medical Press, 2021-08-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1178-7066
• Keywords: inr; periprocedural; pharmacogenetics; pharmacogenomics; warfarin; Therapeutics. Pharmacology; RM1-950
• Source: Pharmacogenomics and Personalized Medicine, Vol Volume 14, Pp 1069-1080 (2021)

Islam Eljilany,1 Mohamed Elarref,2 Nabil Shallik,2- 5 Abdel-Naser Elzouki,6- 8 Loulia Bader,1 Ahmed El-Bardissy,9 Osama Abdelsamad,10 Daoud Al-Badriyeh,1 Larisa H Cavallari,11 Hazem Elewa1,10,12 1College of Pharmacy, QU Health, Qatar University, Doha, Qatar; 2Department of Anesthesia, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; 3Department of Anesthesia, Faculty of Medicine, Tanta University, Tanta, Egypt; 4Department of Clinical Anesthesia, College of Medicine, Qatar University, Doha, Qatar; 5Department of Clinical Anesthesia, Weill Cornell Medical College, Doha, Qatar; 6Department of Medicine, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; 7Department of Internal Medicine, College of Medicine, Qatar University, Doha, Qatar; 8Department of Internal Medicine, Weill Cornell Medical College, Doha, Qatar; 9Department of Pharmacy, Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar; 10Department of Pharmacy, Al Wakra Hospital, Hamad Medical Corporation, Doha, Qatar; 11Department of Pharmacotherapy and Translation Research, Center for Pharmacogenomics and Precision Medicine, College of Pharmacy, University of Florida, Gainesville, FL, USA; 12Biomedical and Pharmaceutical Research Unit, QU Health, Qatar University, Doha, QatarCorrespondence: Hazem ElewaBiomedical and Pharmaceutical Research Unit, QU Health, Qatar University, P.O. Box 2713, Doha, QatarTel [phone]Fax [phone]Email [e-mail]: 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.Keywords: INR, periprocedural, pharmacogenetics, pharmacogenomics, warfarin