CONTRIBUTION OF GENETIC FACTORS TO THE DEVELOPMENT OF CENTRAL VENOUS THROMBOSIS AND POSSIBILITIES OF INDIVIDUALIZING THERAPY

Abstract

The aim of the research. To determine the contribution of genetic factors to the development of central venous thrombosis (CVT), as well as to identify changes in the biotransformation system of drugs used for its treatment and secondary prevention.
Materials and methods. The study included 30 people: patients with clinical signs suspicious for CVT, as well as patients with stroke of unknown etiology. To verify CVT, computed tomography of the brain with bolus intravenous contrast was performed. In 11 people with confirmed CVT, a genetic study of the hemostasis system and the biotransformation and detoxification system was performed to select individual therapy.
Results. The study found that all patients with verified CVT (n = 11) had polymorphisms in the genes of the hemostasis system. The most common polymorphisms were those of the plasminogen activator inhibitor PAI-1 (10 patients out of 11) and methylenetetrahydrofolate reductase (11 patients out of 11) genes. All patients with confirmed CVT underwent a genetic study of the detoxification and biotransformation system. This analysis allowed: 1) to determine the type of warfarin metabolism, which helped to personalize the initial dose of this drug, minimizing adverse events; 2) to determine the necessary drug (acetylsalicylic acid/clopidogrel) for secondary prevention of CVT in cases of thrombus regression. Thus, aspirin resistance was verified in 4 patients; allelic variants of CYP2C19 were detected in 5 patients, determining low enzymatic activity of cytochrome and, as a result, leading to a decrease in the antiplatelet effect of clopidogrel.
Conclusion. The study of hemostasis system polymorphisms confirms the theoretical and practical significance of genetic testing in patients with CVT. The study of the detoxification and biotransformation system allows for a personalized approach to treatment and reduces healthcare system costs aimed at combating undesirable effects of therapy, confirming the economic significance of the analysis.