Abstract
Indirect anticoagulants such as warfarin are the ‘gold standard’ for prevention and treatment of thromboembolic complications in patients at risk (in atrial fibrillation of valvular and nonvalvular etiology, the presence of artificial heart valves, orthopedic and trauma interventions, and other pathological conditions). A wide range of doses required to achieve a therapeutic effect indicates the need for a personalized approach to the appointment of warfarin. In addition to the dependence on the patient's clinical characteristics (sex, age, smoking status, diagnosis), there is a clear association between the warfarin dose and the carriage of certain allelic variants of key genes that makes it possible to apply molecular genetic testing for individual dose adjustment. This provides a more rapid target anticoagulant effect and also reduces the risk of bleeding associated with a possible overdose of warfarin. Implementation of this approach will allow more wide and safe application of indirect anticoagulants in Russia for needy patients.
Highlights
Indirect anticoagulants such as warfarin are the ‘gold standard’ for prevention and treatment of thromboembolic complications in patients at risk
Review Introduction Pharmacogenomics is an important part of personalized medicine which implies that a physician chooses drugs and their doses taking into account individual genetic characteristics of a patient (Figure 1)
Coding singlenucleotide substitution in the CALU gene (Arg4Gln), which presumably provides an increase in dose in patients carrying alleles *1/*1 of the CYP2C9 gene and haplotype BB of the vitamin K-epoxide reductase complex subunit 1 gene (VKORC1) gene, was not significantly associated with the warfarin dose in the study of Wadelius et al [14,59]
Summary
It is shown that the therapeutic dose of warfarin is influenced by many factors, of which genetic factors contribute more than 50%. Haplotypes A and B of the VKORC1 gene make the main contribution to the choice of warfarin dose and should be used for the preliminary genetic examination. The presence of ‘slow’ alleles of the CYP2C9 gene (CYP2C9*2, CYP2C9*3) in a heterozygous state had no reliable effect on the warfarin dose. Their identification is necessary to assess the risk of bleeding. The influence on the dose is reliable, and the risk of complications significantly increases for carriers of the homozygous ‘slow’ CYP2C9 alleles; the frequency of the *2/*2 and *3/*3 genotypes in Western Siberia, to our Patient Medical examination
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