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Clinical Orthopaedics and Related Research®

Erschienen in:

01.07.2009 | Original Article

VKORC1 Variant Genotypes Influence Warfarin Response in Patients Undergoing Total Joint Arthroplasty: A Pilot Study

verfasst von: Alejandro González Della Valle, MD, Saurabh Khakharia, MD, Charles J. Glueck, MD, Nicole Taveras, BS, MS, Ping Wang, PhD, Robert N. Fontaine, PhD, Eduardo A. Salvati, MD

Erschienen in: Clinical Orthopaedics and Related Research® | Ausgabe 7/2009

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Abstract

Warfarin dosing algorithms do not account for genetic mutations that can affect anticoagulation response. We retrospectively assessed to what extent the VKORC1 variant genotype would alter the likelihood of being a hyperresponder or hyporesponder to warfarin in patients undergoing total joint arthroplasty. We used the international normalized ratio (INR) on the third postoperative day of 3.0 or greater to define warfarin hyperresponders and 1.07 or less to define hyporesponders. A control group of normal responders was identified. From a cohort of 1125 patients receiving warfarin thromboprophylaxis, we identified 30 free of predisposing factors that could affect warfarin response: 10 hyperresponders, eight hyporesponders, and 12 normal responders. Homozygous carriers of the VKORC1 mutant AA genotype were more likely (compared with carriers of GA or GG genotypes) to be hyperresponders (odds ratio, 7.5; 95% confidence interval, 1.04–54.1). Homozygous carriers of the GG (normal) genotype were more likely (compared with carriers of AA or GA genotypes) to be hyporesponders (odds ratio, 9; 95% confidence interval, 1.14–71). Preoperative screening for the VKORC-1 genotype could identify patients with a greater potential for being a hyperresponder or hyporesponder to warfarin. This may allow an adjusted pharmacogenetic-based warfarin dose to optimize anticoagulation, reducing postoperative risks of bleeding and thrombosis or embolism.

Level of Evidence: Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

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Titel: VKORC1 Variant Genotypes Influence Warfarin Response in Patients Undergoing Total Joint Arthroplasty: A Pilot Study
verfasst von: Alejandro González Della Valle, MD
Saurabh Khakharia, MD
Charles J. Glueck, MD
Nicole Taveras, BS, MS
Ping Wang, PhD
Robert N. Fontaine, PhD
Eduardo A. Salvati, MD
Publikationsdatum: 01.07.2009
Verlag: Springer-Verlag
Erschienen in: Clinical Orthopaedics and Related Research® / Ausgabe 7/2009
Print ISSN: 0009-921X
Elektronische ISSN: 1528-1132
DOI: https://doi.org/10.1007/s11999-008-0641-5

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