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

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Clinical Orthopaedics and Related Research®

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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Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, Hospital for Special Surgery, 535 East 70th Street, New York, NY, 10021, USA

    Alejandro González Della Valle MD, Saurabh Khakharia MD, Nicole Taveras BS, MS & Eduardo A. Salvati MD

  2. Cholesterol Center, Jewish Hospital of Cincinnati, Cincinnati, OH, USA

    Charles J. Glueck MD & Ping Wang PhD

  3. Molecular Diagnostic Laboratories, Cincinnati, OH, USA

    Robert N. Fontaine PhD

Authors
  1. Alejandro González Della Valle MD
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  2. Saurabh Khakharia MD
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  3. Charles J. Glueck MD
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  4. Nicole Taveras BS, MS
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  5. Ping Wang PhD
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  6. Robert N. Fontaine PhD
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  7. Eduardo A. Salvati MD
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Corresponding author

Correspondence to Alejandro González Della Valle MD.

Additional information

One or more of the authors (EAS, AGDV, CJG) have received funding from a Knee Society grant.

Each author certifies that his or her institution has approved the human protocol for this investigation, that all investigations were conducted in conformity with ethical principles of research, and that informed consent for participation in the study was obtained.

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González Della Valle, A., Khakharia, S., Glueck, C.J. et al. VKORC1 Variant Genotypes Influence Warfarin Response in Patients Undergoing Total Joint Arthroplasty: A Pilot Study. Clin Orthop Relat Res 467, 1773–1780 (2009). https://doi.org/10.1007/s11999-008-0641-5

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  • DOI: https://doi.org/10.1007/s11999-008-0641-5

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