PHARMACOGENETICS OF WARFARIN: CURRENT STATUS OF THE ISSUE. LECTURE

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Abstract

Aim. To provide a scientific review of current data on pharmacogenetic aspects of antithrombotic therapy with warfarin. Materials and methods. To write this review we conducted searching for domestic and foreign publications in Russian and international search systems (PubMed, eLibrary, etc.) since 2000. Results. In recent years a social and economic relevance of thrombotic complications in patients with cardiovascular diseases is steadily increasing. The major drugs for long-term, in some cases life-long, thromboprophylaxis are oral anticoagulants. Despite the appearance of novel direct acting oral anticoagulants on the pharmaceutical market, vitamin K antagonist warfarin does not lose its position. In a number of clinical situations this drug has no alternative. Disadvantages of warfarin include its narrow therapeutic index and therefore the need for careful continuous laboratory monitoring of the blood coagulation system. An overdose of warfarin can cause serious bleeding complications which develop more often at the beginning of treatment. For this reason, a personalized approach to selecting the initial warfarin dose is of particular importance. When selecting the drug dose along with clinical factors genetic ones are also of great importance. The presence of genetic polymorphisms in genes that control warfarin pharmacokinetics and pharmacodynamics can be decisive. Warfarin dosing algorithms are available, however, new data that are recently emerging, dictate the need for their modification, including taking into account ethnic characteristics of patients. Different ethnic groups have features in a contribution of various genes and genetic polymorphisms to manifestation of warfarin’s anticoagulant effect. It was shown that identification of CYP4F2 genetic polymorphisms in African- Americans is not necessary, whereas for Europeans it is a prerequisite. At the same time, determining genetic variants of CYP2C rs12777823 is important for African Americans, but it should not be determined for Europeans. Conclusions. Warfarin remains one of the most commonly prescribed anticoagulants in routine clinical practice. Its safety is ensured by individual selection of initial and maintenance doses by use of algorithms based on clinical and genetic factors. The emergence of new data on warfarin pharmacogenetics allows to personalize the drug dosing to the maximum, which ensures the efficacy and safety of anticoagulant therapy.

About the authors

Olga A. Mubarakshina

Burdenko Voronezh State Medical University

Email: mubarakshina@mail.ru
канд. мед. наук, доц. каф. клинической фармакологии Воронеж, Россия

Marina N. Somova

Burdenko Voronezh State Medical University

канд. мед. наук, доц. каф. клинической фармакологии Воронеж, Россия

Galina A. Batishcheva

Burdenko Voronezh State Medical University

д-р мед. наук, проф., зав. каф. клинической фармакологии Воронеж, Россия

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