IntroductionDifficulties in non-vitamin K anticoagulant (NOAC) administration in acute stroke can be associated with changes in pharmacokinetic parameters of NOAC such as biotransformation, distribution, and excretion. Therefore, obtaining data on pharmacokinetics of NOAC and factors that affect it may help develop algorithms for personalized use of this drug class in patients with acute cardioembolic stroke.Patients and methodsPharmacokinetics of apixaban in patients with acute stroke was studied earlier by Kryukov et al. The present study enrolled 17 patients with cardioembolic stroke, who received 5 mg of apixaban. In order to evaluate the pharmacokinetic parameters of apixaban, venous blood samples were collected before taking 5 mg of apixaban (point 0) and 1, 2, 3, 4, 10, and 12 hours after drug intake. Blood samples were centrifuged at 3000 rpm for 15 minutes. Separate plasma was aliquoted in Eppendorf tubes and frozen at −70°C until analysis. High-performance liquid chromatography mass spectrometry analysis was used to determine apixaban plasma concentration. Genotyping was performed by real-time polymerase chain reaction. CYP3A isoenzyme group activity was evaluated by determining urinary concentration of endogenous substrate of the enzyme and its metabolite (6-β-hydroxycortisol to cortisol ratio). Statistical analysis was performed using SPSS Statistics version 20.0. The protocol of this study was reviewed and approved by the ethics committee; patients or their representatives signed an informed consent.ResultsABCB1 (rs1045642 and rs4148738) gene polymorphisms do not affect the pharmacokinetics of apixaban as well as CYP3A5 (rs776746) gene polymorphisms. Apixaban pharmacokinetics in groups with different genotypes did not differ statistically significantly. Correlation analysis showed no statistically significant relationship between pharmacokinetic parameters of apixaban and the metabolic activity of CYP3A.ConclusionQuestions such as depending on genotyping results for apixaban dosing and implementation of express genotyping in clinical practice remain open for NOACs. Large population studies are required to clarify the clinical significance of genotyping for this drug class.

Aim. To search for new pharmacogenetic biomarkers of bleeding risk in patients taking rivaroxaban and dabigatran for different indications: atrial fibrillation, endoprosthesis of large joints of lower limbs.Material and methods. The study enrolled 29 patients (17 patients received dabigatran and 12 –rivaroxaban), who had hemorrhagic complications during taking direct oral anticoagulants. To find new pharmacogenetic biomarkers of bleeding risk, a next generation sequencing (NGS) was performed for selected candidate genes.Results. Among the patients with bleeding who received dabigatran, 13 variants of the nucleotide sequence showed statistically significant deviation from the population values: 11 in the CES1 gene and 2 in the ABCB1 gene. Among the patients with bleeding who received rivaroxaban, 7 variants of nucleotide sequence showed significant deviation: 4 in the ABCG2 gene, 2 in the CYP3A4 gene, and 1 in the ABCB1 gene.Conclusion. The identified in this study polymorphisms of candidate genes ABCB1, ABCG2, CES1, CYP3A4 were associated with the risk of bleeding in patients taking rivaroxaban and dabigatran. It makes an important contribution to the pharmacogenetics of direct oral anticoagulants and require additional assessment of clinical significance in further studies.

Лечение и профилактика кардиоэмболического ин-сульта (КЭИ) -весьма актуальная проблема современной клинической ангионеврологии. В немалой степени это обу-словлено значительной распространенностью КЭИ среди всех типов инсульта, что было показано с помощью совре-менных методов исследования, визуализирующих тромбоз левого предсердия (в частности, при трансэзофагальной эхокардиографии -ЭхоКГ), потенциальной возможностью профилактики (антитромботические препараты снижают вероятность рецидива), а также в целом худшим прогнозом в отношении как летальности, так и инвалидизации, чем при других типах ишемического инсульта (ИИ) [1,2]. Этот тип острых нарушений мозгового кровообращения (ОНМК) составляет около 20% всех транзиторных ишеми-ческих атак (ТИА) и ИИ и 12-31% всех ИИ [2][3][4]. При этом в середине XX в. на кардиоцеребральные эмболии приходи-лось всего 3-8% всех ОНМК; столь значительное увеличе-ние их доли стало следствием внедрения в клиническую пра-ктику ультразвуковых методов исследования и компьютер-ных технологий, существенно улучивших диагностику

Background Atrial fibrillation (AF) is a common comorbidity in around 10–15% of patients (pts) with CKD, while 30% of those with AF have CKD. In pts with advanced stages of CKD, safety and efficacy profiles of novel oral anticoagulants, in particular rivaroxaban, have been understudied. Purpose To evaluate safety and efficacy of rivaroxaban in pts with stage 4 CKD or a transient reduction in glomerular filtration rate (GFR) to 15–29 ml/min/1.73 m2. Materials and methods Data of 3,500 pts with nonvalvular AF in cardiovascular units for the period from 2017 to 2019 were analyzed. Of these, 507 (15%) showed a decrease in GFR to 29–15 ml/min/1.73 m2. 109 (3.1%) pts enrolled in the study (in accordance with inclusion criteria) and were randomized in a 2: 1 fashion to either the 15 mg rivaroxaban (n=74) or warfarin (n=36) group. The pts had either not previously been taking anticoagulants, or TTR was <65% in the case of taking warfarin. The average follow-up period was 18 months. Visits took place every 3 months, when compliance, haemoglobin were checked and GFR calculation was carried out. Primary endpoint: development of major and minor bleeding on the BARC scale. Secondary endpoints: thromboembolic events, cardiovascular mortality and all-cause mortality. Results The pts were of similar clinical and demographic profile. The median age was 77 years with 32 men in the rivaroxaban group and 14 in the warfarin group. The average CHA2DS2-VASc score was 4.6 and 4.7 (n/s) in the rivaroxaban and warfarin group, respectively, while the average HAS-BLED score was 3 (n/s) in both. Pts taking warfarin were significantly more likely to develop minor bleedings: 26 (72%) vs 27 (37%) in the rivaroxaban group, p=0.001. There were not detected significant differences in the ratio of major bleedings (warfarin 3 (8.3%) versus rivaroxaban 2 (2.7%) cases, p=0.3). No significant differences at secondary endpoints were observed. In the warfarin group, 1 (2.8%) ischemic stroke and 1 fatal haemorrhagic stroke occurred. In the rivaroxaban group, 1 (1.4%) ischemic stroke occurred during a 5-day break in taking the anticoagulant. 5 (6.9%) pts in the rivaroxaban group developed ACS, vs 1 (2.8%) in the warfarin group (n/s). 2 (2.7%) pts died from myocardial infarction in the rivaroxaban group and 1 (2.8%) - in the warfarin group (n/s). Mortality from all causes was 5 (6.6%) in the rivaroxaban group and 3 (8.3%) in the warfarin group (n/s). In the rivaroxaban group, GFR (CG formula) improved significantly more since the 3rd month of observation (in the 18th month of observation, the median value was 35.0 [29.0; 39.5] ml/min/1.73 m2 vs 27.0 [21.5; 31.5] ml/min/1.73 m2 in the warfarin group, p<0.001). Conclusion Significantly more pts within the warfarin group had minor bleedings. Pts during warfarin and rivaroxaban therapy showed an improvement in glomerular filtration, which was more pronounced in the rivaroxaban group. Funding Acknowledgement Type of funding source: None

Patients with COVID-19 are typically characterized by severe lung injury with the development of acute respiratory failure. However, in some patients, subjective well-being may remain relatively satisfactory for a long time and, despite severe hypoxemia, they do not complain of shortness of breath. Case report. We observed a 65-year-old man hospitalized with severe SARS-CoV-2 pneumonia, low level of blood oxygen saturation, but at the same time without complaints of shortness of breath. Only as the disease progressed with a decrease in oxygen saturation when breathing atmospheric air (SpO2 ) lower than 85% he began to notice a feeling of lack of air. The patient’s condition worsened and as a result, he died in the intensive care unit from multiple organ failure. Discussion. This case clearly illustrates one more feature of the course of pneumonia associated with the novel SARSCoV-2 coronavirus and shows that SpO2 measurement is one of the leading objective criterion that allows a doctor to assess the real severity of a patient’s condition with COVID-19.