Long-term therapy with the use of indirect anticoagulants. The modern approach to the problem

Novikova Ia.V.; Shevela A.I.; Morozov V.V.; Seriapina Iu.V.

doi:https://doi.org/

Novikova Ia.V.

Institut khimicheskoĭ biologii i fundamental'noĭ meditsiny SO RAN, Novosibirsk

Shevela A.I.

The Center of New Medical Technologies Institute of Chemical Biology and Fundamental Medicine, The Russian Academy of Sciences, Siberian Branch Novosibirsk, Russia

ORCID: 0000-0002-3164-9377

Morozov V.V.

The Center of New Medical Technologies Institute of Chemical Biology and Fundamental Medicine, The Russian Academy of Sciences, Siberian Branch Novosibirsk, Russia

Seriapina Iu.V.

Institut khimicheskoĭ biologii i fundamental'noĭ meditsiny SO RAN, Novosibirsk

Long-term therapy with the use of indirect anticoagulants. The modern approach to the problem

Authors:

Novikova Ia.V., Shevela A.I., Morozov V.V., Seriapina Iu.V.

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Journal: Journal of Venous Disorders. 2012;6(3): 40‑45

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To cite this article:

Novikova IaV, Shevela AI, Morozov VV, Seriapina IuV. Long-term therapy with the use of indirect anticoagulants. The modern approach to the problem. Journal of Venous Disorders. 2012;6(3):40‑45. (In Russ.)

Подписка 2026 Флебология (Journal of Venous Disorders)

Использование инфографики авторами научных работ

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Abstract:

The objective of the present work was to improve the efficacy and safety of long-term anticoagulation therapy with the use of the methods for molecular-genetic probing of the warfarin metabolism system. The main study group included 156 patients in whom peculiarities of warfarin metabolism were elucidated in a genetic study. The control group was comprised of 150 patients treated in accordance with standard recommendations. The patients remained under the observation during 5 years. The following genes involved in the regulation of the warfarin metabolism system were studied using PCR and RFLP: CYP2C9*2, C430T, CYP2C9*3, A10075C, VKORCI C+1173T. The samples of peripheral venous blood were used for the purpose. The statistical analysis of the data obtained in the study was carried out with a personal computer using the Statistica 6.0 software package. The frequency of alleles and genotypes were determined by direct counting. The deviation of genotype distribution of the studied DNA polymorphisms from the Hardy-Weinberg canonical distribution was estimated using a computer software. It was shown that the patients of the main group were characterized by the prevalence of wild type CYP2C*9 and CYP2C9*3 genes in conjunction with the heterozygous variant of the VKORC1 gene. This finding suggests the predominance of "standard" metabolizers of warfarin. The study demonstrated that the period of induction in the patients of the main group was twice shorter than in controls. Also, the therapeutic doses of warfarin were stably achieved 1.3 times more frequently in the patients who underwent genotyping. The correlation analysis of the relationship between genotyping data and the dosage of therapy allowed determining mean weekly doses of warfarin for different genotype variants. The maximum dose of warfarin was estimated to be 40.7 mg per week in the carriers of the wild type of all the studied genes. It is concluded that the molecular-genetic study of individual peculiarities of warfarin metabolism makes it possible to shorten the period of induction, reduce the risk of hemorrhagic complications (including the fatal ones), and improve the accuracy of prediction of the response to the treatment.

Keywords:

warfarin

genetic study

polymorphism

Authors:

Novikova Ia.V.

Institut khimicheskoĭ biologii i fundamental'noĭ meditsiny SO RAN, Novosibirsk

Shevela A.I.

The Center of New Medical Technologies Institute of Chemical Biology and Fundamental Medicine, The Russian Academy of Sciences, Siberian Branch Novosibirsk, Russia

ORCID: 0000-0002-3164-9377

Morozov V.V.

The Center of New Medical Technologies Institute of Chemical Biology and Fundamental Medicine, The Russian Academy of Sciences, Siberian Branch Novosibirsk, Russia

Seriapina Iu.V.

Institut khimicheskoĭ biologii i fundamental'noĭ meditsiny SO RAN, Novosibirsk

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References:

Scott S.A., Khasawneh R., Peter I., Kornreich R., Desnick R.J. Combined CYP2C9, VKORC1 and CYP4F2 frequencies among racial and ethnic groups. Pharmacogenomics 2010; 11: 6: 781-791.
Ross K.A., Bigham A.W., Edwards M., Gozdzik A., Suarez-Kurtz G., Parra E.J. Worldwide allele frequency distribution of four polymorphisms associated with warfarin dose requirements. J Hum Genet 2010; 55: 9: 582-589.
Cen H.J., Zeng W.T., Leng X.Y., Huang M., Chen X., Li J.L., Huang Z.Y., Bi H.C., Wang X.D., He Y.L., He F., Zhou R.N., Zheng Q.S., Zhao L.Z. CYP4F2 rs2108622: a minor significant genetic factor of warfarin dose in Han Chinese patients with mechanical heart valve replacement. Br J Clin Pharmacol 2010; 70: 2: 234-240.
Choi J.R.,Kim J.O.,Kang D.R., Yoon S.A., Shin J.Y., Zhang X., Roh M.O., Hong H.J., Wang Y.P., Jo K.H., Lee K.S., Yun H.J., Oh Y.S., Yoo K.D., Jeon H.G., Lee Y.S., Kang T.S., Park H.J., Chung M.W., Kang J.H. Proposal of pharmacogenetics-based warfarin dosing algorithm in Korean patients. J Hum Genet 2011; 56: 4: 290-295.
Zambon C.F., Pengo V., Padrini R., Basso D., Schiavon S., Fogar P., Nisi A., Frigo A.C., Moz S., Pelloso M., Plebani M. VKORC1, CYP2C9 and CYP4F2 genetic-based algorithm for warfarin dosing: an Italian retrospective study. Pharmacogenomics 2011; 12: 1: 15-25.
Singh O., Sandanaraj E., Subramanian K., Lee L.H., Chowbay B. Influence of CYP4F2 rs2108622 (V433M) on warfarin dose requirement in Asian patients. Drug Metab Pharmacokinet 2011; 26: 2: 130-136.
Johnson E.G., Horne B.D., Carlquist J.F., Anderson J.L. Genotype-based dosing algorithms for warfarin therapy: data review and recommendations. Mol Diagn Ther 2011.
Marin-Leblanc M., Perreault S., Bahroun I., Lapointe M., Mongrain I., Provost S., Turgeon J., Talajic M., Brugada R., Phillips M., Tardif J.C., Dubé M.P. Validation of warfarin pharmacogenetic algorithms in clinical practice. Pharmacogenomics 2012; 13: 1: 21-29.
Nishimura F., Tokuda M., Sasaki D., Mori S., Tsuruda K., Hasegawa H., Yanagihara K., Kamihira S. An instructive case suggesting warfarin resistance which is independent on the regulation of the CYP2C9 and VKORC1 genotype. Rinsho Byori 2011; 59: 12: 1087-1090.
Maniatis T., Frich E., Sembruk Dzh. Molekulyarnoe klonirovanie. M: Mir 1984; 480.