Key result
Genetic polymorphisms in CYP2C9 and VKOR1 account for about one third of the variation in dose requirements for Vitamin K antagonists, alongside various environmental factors.
Various environmental and genetic factors significantly influence the anticoagulant effect of VKAs, highlighting the need for careful monitoring and patient education.
Highlights dosing variability requiring INR monitoring; leaves open whether routine genotyping improves VKA outcomes.
Vitamin K antagonists (VKAs) are widely used for the primary and secondary prevention of thromboembolism, their anticoagulant effect being monitored through INR. Achieving and maintaining a stable anticoagulation status is challenging, because of the narrow therapeutic range, and of the extremely variable individual response to therapy. Environmental factors such as age, gender, body mass, diet, herbal supplements, drugs, pre-existing pathology, as well as genetic factors can substantially influence the anticoagulant effect of VKAs. The main genetic factors that contribute to individual variability in response to VKAs are genetic polymorphisms in genes influencing VKAs’ metabolism (CYP2C9) and pharmacodynamic response (VKOR1) and account for about one third in the variation of warfarin and analogues dose requirement. Systematic genotyping of patients requiring warfarin therapy is still a matter of debate. Although novel oral anticoagulants (direct thrombin and factor Xa inhibitors) seem promising, VKAs are still frequently prescribed, therefore physicians should be aware of the various factors influencing VKAs’ effect, and educational programmes for doctors and patients should be conducted in that respect
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Ioana Brudaşcă (2015) conducted a review in Thromboembolism. Vitamin K antagonists was evaluated. Genetic polymorphisms in CYP2C9 and VKOR1 account for about one third of the variation in dose requirements for Vitamin K antagonists, alongside various environmental factors.
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