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Effect of genetic and patient factors on warfarin pharmacodynamics following warfarin withdrawal: Implications for patients undergoing surgery

Lookup NU author(s): Dr Salah Abohelaika, Dr Hilary Wynne, Dr Peter Avery, Dr Emma Kampouraki, Professor Farhad Kamali

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).


Abstract

Introduction Warfarin therapy is stopped for a fixed period prior to surgery to minimise risk of perioperative bleeding. However, anticoagulation subsides at varying rates among different patients. We evaluated the influence of genetic (CYP2C9 and VKORC1), patient and clinical factors on warfarin clearance and the decline in INR following warfarin withdrawal. Materials and methods 131 patients completing a course of warfarin provided blood samples over 9 days for initial genotyping, and measurement of INR and plasma warfarin enantiomer concentrations. Results S-warfarin clearance was significantly lower in patients with either CYP2C9 single (*2 or *3) or double (*2*2 or *2*3) variant alleles compared to those with wild-type genotype (P<0.001). Regression analysis revealed that patient age (P=0.037) and CYP2C9 *2*2 & *2*3 genotype (P=0.005), but not VKORC1 genotype, significantly affected the time taken for the resumption of normal coagulation (INR value declining to ≤1.5). Conclusions The inter-individual variability in the time needed for normal coagulation to resume following warfarin withdrawal is influenced, in the main, by variance in S-warfarin clearance, which in turn is affected by CYP2C9 polymorphism and age. Cost-effectiveness of pharmacogenetics-based algorithms incorporating CYP2C9 genotype and patient age could be increased if used not only to guide dosing decisions but also estimation of the correct length of time needed for individual patients to stop taking warfarin prior to surgery.


Publication metadata

Author(s): Abohelaika S, Wynne H, Avery P, Kampouraki E, Kamali F

Publication type: Article

Publication status: Published

Journal: Thrombosis Research

Year: 2018

Volume: 171

Pages: 167-170

Print publication date: 01/11/2018

Online publication date: 01/10/2018

Acceptance date: 28/09/2018

Date deposited: 28/09/2018

ISSN (print): 0049-3848

ISSN (electronic): 1879-2472

Publisher: Elsevier

URL: https://doi.org/10.1016/j.thromres.2018.09.064

DOI: 10.1016/j.thromres.2018.09.064


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