Key result
Homozygous carriers of the VKORC1 mutant AA genotype were significantly more likely to be hyperresponders to warfarin compared with carriers of GA or GG genotypes (OR 7.5).
Why the study?
Does VKORC1 variant genotype influence the likelihood of being a hyperresponder or hyporesponder to warfarin in patients undergoing total joint arthroplasty?
Case-Control (n=30)
No
Does VKORC1 variant genotype influence the likelihood of being a hyperresponder or hyporesponder to warfarin in patients undergoing total joint arthroplasty?
Odds Ratio: 7.5 (95% CI 1.04–54.1)
Preoperative screening for the VKORC1 genotype in patients undergoing total joint arthroplasty can identify those at risk of hyper- or hypo-response to warfarin, potentially allowing for pharmacogenetic-based dosing to optimize anticoagulation.
VKORC1 AA genotype was associated with warfarin hyperresponse; hypothesis-generating for genotyping-guided dosing, should not yet change practice.
UNLABELLED: 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.
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Valle et al. (2008) conducted a case-control in Total joint arthroplasty requiring warfarin thromboprophylaxis (n=30). VKORC1 mutant AA genotype vs. VKORC1 GA or GG genotypes was evaluated on Likelihood of being a hyperresponder to warfarin (INR ≥ 3.0 on postoperative day 3) (OR 7.5, 95% CI 1.04-54.1). Homozygous carriers of the VKORC1 mutant AA genotype were significantly more likely to be hyperresponders to warfarin compared with carriers of GA or GG genotypes (OR 7.5).
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