The article is devoted to the discussion of modern approaches to the use of laboratory methods to improve the tactics of using direct oral anticoagulants (DOACs) therapy. Clinical situations in which it may be reasonable to use data on the blood concentration of DOACs are given, including very old age, a marked deviation from the norm of body weight or impaired renal function. Data on the role of measuring the blood level of DOACs are considered in cases of the development of diseases or complications in which information is required on the preservation of the anticoagulant effect of DOACs, for example, in the development of severe bleeding or the need for urgent surgical intervention. The advantages and limitations of modern laboratory methods for assessing the blood concentration of DOACs are discussed. It is emphasized that one of the main advantages of using DOACs is the absence of the need to monitor laboratory parameters in most patients. Data from pharmacological studies are presented that may be useful in explaining the mechanisms that determine the higher safety of some DOACs compared to others. Promising methods for assessing the blood level of DOACs, as well as the possibility of using less specific reagents for assessing the concentration of DOACs, are considered. The possibility of using less specific, but more accessible methods for assessing the blood concentration of factor Xa inhibitors, in particular, a reagent for assessing the level of the antifactor, which is used to determine the blood level of heparin, is being considered. The opinions of experts on the role of assessing the blood level of DOACs and the possibility of tactics for selecting doses of DOACs based on laboratory analysis data are given.

Modern professional education of internists is being updated at an intensive pace. This is primarily due to the fact that medicine and its technologies do not stand still, rushing into a high-tech future. In this regard, people have great hopes for highly effective conservative care, including for hematological diseases. Basic research on the mechanisms of blood clotting has greatly improved the knowledge of complex pathophysiology. These advances have led to a more complex decision-making process, which is reflected in the complex effect of hemostasis imbalance on the complement system, immunity and inflammation, and hence on the treatment of hemostasis disorders. Given this rapidly changing context, optimal educational activities are needed to disseminate knowledge among health professionals and develop their competencies in this field. Specialized professional associations can provide support and training offerings that facilitate access to relevant resources and tools to enable high-quality, up-todate basic and clinical research.

Modern teaching to young physicians has become increasingly limited because of rising clinical workload, due to the epidemiological situation, new requirements for medical documentation, the lack of a clear timetable of working hours and other educational features. Additionally, today’s residents expect that the training sessions will provide focused content integrated into their clinical workflow. One of the classical teaching methods that is ideally suited to meet these needs is a focused thematic training session, usually conducted with the help of simple but accessible visual aids and extensive audience participation. However, most listeners will benefit from structured content and guidance on the delivery of this content, also known as a learning scenario. A good learning scenario resident’s misconception, highlights a certain number of learning moments, uses strategies to engage students and provides a cognitive basis for teaching a topic that the teacher can improve over time. The proposed pedagogical concept of teaching sections of clinical hemostasiology for residents in the specialty "Therapy" orients the professional and cognitive interest of a young specialist against the background of constantly updated new knowledge in this field with the integration of scenarios of the content of training into clinical practice.

ПРОГНОЗИРОВАНИЕ ГИПОТРОФИИ НОВОРОЖДЕННЫХ У БЕРЕМЕННЫХ С ЗАДЕРЖКОЙ РОСТА ПЛОДА1 Южно-Уральский государственный медицинский университет, г.Челябинск Фартунина Ю.В. 1 , Вереина Н

Introduction. An important problem of modern obstetrics is the development and improvement of methods for predicting fetal growth retardation (FGR) and pregnancy outcomes in this pathology, since there are no proven effective treatments for FGR. Purpose of the study — to develop prediction criteria for newborn hypotrophy and cumulative adverse perinatal outcome in pregnant women with FGR. Objective. To identify key predictive factors for adverse perinatal outcomes in pregnancy complicated by FGR. Material and methods. A case-control, cohort-based study was conducted that included 155 pregnant women with FGR, who were divided into two groups after delivery: Group 1 included 90 patients with neonatal hypotrophy and Group 2 included 65 patients without neonatal hypotrophy. A comprehensive analysis of clinical and anamnestic, laboratory and instrumental data, peculiarities of the course of pregnancy and perinatal outcomes was performed. FGR was determined on the basis of ultrasound fetometry. Results. Factors associated with neonatal hypotrophy and unfavorable perinatal outcome were: impaired blood flow in the uterine arteries and/or umbilical artery, early preeclampsia and scarcity of water. Protective factors were antibacterial therapy for intrauterine infection, administration of low-molecular-weight heparin in the first trimester, and acetylsalicylic acid starting from the 12th to 16th weeks of gestation. Conclusion. The most promising measures in the prevention of FGR and adverse perinatal outcomes in this pathology may be timely prescription of antithrombotic correction and treatment of genital infections.

Aim. To quantify the risk of venous thromboembolism (VTE) in hospitalized patients, depending on the severity of heart failure (HF).Material and methods. Current cross-sectional study included 132 patients hospitalized in the cardiology department in 2019. All participants were divided into 2 groups: group 1 (n=48) — patients with class I-II HF; group 2 (n=84) — patients with class III-IV HF. A total quantitative assessment of the VTE risk was carried out according to the Caprini risk scoring method.Results. All patients hospitalized in the cardiology department, regardless of HF class, had a moderate and high risk of VTE and required prophylactic anticoagulation. High VTE risk had 85% of patients with class I-II HF; 97,6% — patients with a class III-IV HF. Mean score of ≥10 was observed in every fifth patient. Atrial fibrillation requiring long-term anticoagulant therapy was observed in 51,5% of patients. There were no absolute contraindications for parenteral prophylactic anticoagulation at the time of hospitalization in the study population.Conclusion. All patients admitted to the cardiology department had a moderate and high according to the Caprini risk score, regardless of HF class. More than half of the patients had indications for long-term anticoagulant therapy. The remaining patients required the parenteral prophylactic anticoagulation.

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): South Ural State Medical University Introduction. The interaction of metabolic and cardiovascular factors, united by common mechanisms of mutual interference, determines the modern concept of cardiometabolic risk. It is important to study the determinants of cardiometabolic risk factors in different phenotypes of overweight and obesity among young adults. Purpose. To study cardiometabolic risk factors in various phenotypes of overweight and obesity among young adults. Methods. Study design: cross-sectional study. The study included 251 patients. All patients were divided into 4 groups: gr. 1 - metabolically healthy individuals with normal body weight (n = 62), aged 24.5 [22-31] years; gr. 2 - metabolically unhealthy individuals with normal body weight (n = 57), aged 28 [23-38] years; gr. 3 - metabolically healthy overweight/obesity (n = 16), aged 30 [24-36] years; gr. 4 - metabolically unhealthy overweight/obesity (n = 116), aged 36 [28.5-41] years. Statistical methods: MedCalc statistical software package (2020). p < 0.05 were taken as statistically significant. Results. The most significant changes of carbohydrate and lipid metabolism and some hemostasis parameters with adipokine imbalance were found in metabolically unhealthy overweight/obesity (gr. 4): the highest concentrations of leptin (ng/ml): 37.9 [13.0-63.4] vs 10.0 [5.1-15.5] – gr.1; 9.5 [5.5-21.5] – gr. 2; 25.7 [4.7-37.2] – gr. 3, p4-1.2.3 < 0.05; fibrinogen (g/l): 4.0 [3.5-4.6] vs 3.4 [2.9-4.0] – gr. 1, 3.4 [3.1-4.0] – gr. 2, 3.4 [2.6-3.8] – gr. 3, p4-1.2.3 < 0.001; plasminogen activator inhibitor-1 (ng/ml): 464.5 [285.1-628.5] vs 308.2 [211.7-415.7] – gr. 1; 342.3 [222.2-490.0] – gr. 2; 371.0 [273.1-621.0] – gr. 3, p4-1 < 0.001, as well as the lowest concentrations of adiponectin (μg/ml): 7.9 [4.9-10.2] – gr. 3 and 7.9 [5.2-12.4] – gr. 4 compare to gr. 1 – 9.1 [7.5-12.2]) and gr. 2 – 8.7 [7.2-10.5], p3.4-1.2 < 0.05. In young individuals the most significant correlations were found between waist circumference, systolic and diastolic blood pressure - on the one hand, and serum concentrations of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, leptin, fibrinogen, and type 1 plasminogen activator inhibitor, on the other hand. Conclusion. Disorders of lipid and carbohydrate metabolism with adipokine imbalance in young adults determine a higher cardiometabolic risk both in overweight/obese patient and individuals with normal body mass index.

Organization of anticoagulant therapy control plays a key role in ensuring the effectiveness and safety of anticoagulant use. Currently, several models of organization are successfully used in the Russian Federation, which cover more than 23000 patients at high risk for thromboembolic events. There are following common features of the models used: the maximum reduction in the time from the moment of international normalized ratio (INR) testing with a quick communication with a patient for the need to adjust the dose, the ability to sort patients depending on the degree of hypocoagulation and the risks of events with the creation of a personalized approach to treatment, the organization of a shared information space and maintaining a register of patients.

Введение: Задержка роста плода (ЗРП) занимает второе место в структуре причин перинатальной смертности, а ее наличие имеет длительное неблагоприятное влияние на здоровье ребенка. Оценка степени активации системы гемостаза при ЗРП в сопоставлении с клиническими исходами имеет важное значение в понимании патогенеза, улучшении прогнозирования и профилактики этого патологического состояния. Цель исследования: оценить состояние гемостаза у беременных с ЗРП в сравнении с женщинами с физиологическим течением беременности. Материалы и методы: Тип исследования: поперечный срез на базе когортного. В исследование включено 52 беременных. Основная группа — 32 пациентки с ЗРП, выявленной при ультразвуковой фетометрии; контрольная группа — 20 практически здоровых женщин без отягощенного акушерско-гинекологического анамнеза, с физиологически протекавшей беременностью, завершившейся неосложненными родами. Оценку состояния системы гемостаза проводили на сроке 24-32 нед гестации. Результаты: Среди факторов тромботического риска у беременных с ЗРП чаще выявлялось табакокурение во время беременности. Наличие ЗРП было значимо связано с маловодием, генитальной и внутриматочной инфекцией, преэклампсией, нарушениями маточно-плацентарно-плодового кровотока. У женщин с ЗРП обнаружен более высокий уровень фибриногена, а также повышение скорости роста сгустка, больший размер сгустка, более частое формирование спонтанных сгустков в сравнении с контрольной группой. Заключение: У беременных с ЗРП имеется протромботическая готовность плазмы, что может служить основанием для дальнейшей разработки антитромботической коррекции с целью улучшения перинатальных исходов. Background: Fetal growth retardation (FGR) is the second leading cause of perinatal mortality, has a long-term adverse effect on child health. Assessment of hemostasis activation in FGR in comparison with clinical outcomes is important for understanding pathogenesis, improving the prognosis and prevention of this pathological state. Objectives: to assess hemostasis state in pregnant women with FGR compared to women with physiological pregnancy. Patients/Methods: Type of study: crosssectional based on cohort. The study included 52 pregnant women. The main group consisted of 32 patients with FGR diagnosed by ultrasound fetometry; the control group consisted of 20 practically healthy women without burdened obstetric-gynecological history, with physiological pregnancy that ended in uncomplicated childbirth. Hemostasis assessment was carried out at 24-32 weeks of gestation. Results: Smoking during pregnancy as a factor of thrombotic risk was more common in pregnant women with FGR. FGR was significantly associated with oligohydramnios, genital and intrauterine infection, preeclampsia, and placental insufficiency. Women with FGR showed a higher level of fibrinogen, as well as an increased rate of clot growth, clot larger size, and more frequent formation of spontaneous clots in comparison with the control group. Conclusions: Pregnant women with FGR are characterized by prothrombotic state that may be the basis for further development of antithrombotic correction for improving perinatal outcomes.

Introduction: to assess the influence of factors independently associated with arterial and venous thrombosis in women aged 18-44 years outside pregnancy.Material and methods. The case-control study included 319 women: the cases group included 134 patients with verified arterial and venous thrombosis, the control group included 185 patients without thrombosis. inclusion criteria: age 18-44 years; the presence of the first episode of instrumental^ verified arterial or venous thrombosis; consent to participate in the study. Exclusion criteria: pregnancy; the postpartum period up to 6 weeks at the time of thrombosis; mental disorders and mental illness. All women underwent clinical examination, collection of somatic and obstetric history, testing for biochemical parameters, hereditary and acquired thrombophilia. To quantify the independent relationships of risk factors with thrombotic events, the multiple logistic regression method was used.Results. In the group of cases, venous thrombosis was in 75% women, arterial thrombosis - in 25%. Ischemic strokes prevailed in the structure of arterial thrombosis. The most common trigger was the use of estrogen-progestin containing contraceptives in combination with other risk factors. In 23 cases (17.2%) the thrombosis were unprovoked. The proportion of women ≥ 40 years old, smoking intensity; family history of VTE in relatives up to 50 years of age, dyslipidemia, hyperfibrinogenemia, comorbidity, and the presence of thrombophilia met with a higher frequency in the group of cases. Independent factors associated with the development of arterial and venous thrombosis in young women were: the presence of diseases of the gallbladder (OR = 12,1 95% CI 2.5-67.5), cardiovascular diseases (OR = 10.2; 95% CI 3.6-29.1); total cholesterol level (OR = 7.7; 95% CI 4.4-13.5); respiratory diseases (OR = 3.7; 95% CI 1.0-11.5); the use of combined hormonal contraceptives (OR = 3.4; 95% CI 1.7-6.8); varicose veins of the lower extremities (OR = 2.5; 95% CI 1.0-4.9).Conclusion. The identification of the most important risk factors for arterial and venous thrombosis will expand the understanding of the common pathogenetic way of thrombosis in a population of women of childbearing age and improve their personalized prognosis and early prevention.

ФАКТОРЫ РИСКА ТРОМБОТИЧЕСКИХ ОСЛОЖНЕНИЙ У ЖЕНЩИН, ИСПОЛЬЗУЮЩИХ КОМБИНИРОВАННЫЕ ГОРМОНАЛЬНЫЕ КОНТРАЦЕПТИВЫВереина Н.К

61-08 ФАКТОРЫ, АССОЦИИРОВАННЫЕ С ПОРАЖЕНИЕМ ПОЧЕК, ПРИ АРТЕРИАЛЬНОЙ ГИПЕРТЕНЗИИ И АБДОМИНАЛЬНОМ ОЖИРЕНИИ В МОЛОДОМ ВОЗРАСТЕ Чулков Вл.С. 1 , Вереина Н

Objective.We performed a cross-sectional study of risk factors and biomarkers of cardiovascular diseases among young women with hypertensive disorders during pregnancy in comparison with women without hypertension during pregnancy.Design and methods.Altogether 117 women were enrolled, 33 were included in the group of hypertensive disorders during pregnancy, and 44 formed the group without hypertension during pregnancy. The control group consisted of 40 patients. The time interval after delivery was on average 5 to 19 years.Results and conclusions.Women with hypertension during pregnancy developed changes in carbohydrate and lipid metabolism associated with hypertension and abdominal obesity, which are the components of the cluster of the metabolic syndrome. These changes are also accompanied by insulin resistance, hyperinsulinemia, adipokine imbalance, changes in fbrinolysis and more pronounced remodeling of the heart and vessels as target organs in hypertension.

Aim. To carry out a comparative assessment of hemostasis, adipokines levels and markers of endothelial dysfunction in young patients with a variety of components of the metabolic syndrome. Methods. The study included 154 patients aged 18-44 years who were divided into four groups matched for age and sex: the first group - 35 patients with metabolic syndrome, the second group - 25 patients with hypertension without abdominal obesity, the third group - 22 patients with abdominal obesity without hypertension, the fourth group - 72 healthy subjects (control group). We studied the vascular-platelet, coagulation and anticoagulation units of the hemostasis system, the fibrinolytic system, the levels of adipokines and markers of endothelial dysfunction. Results. Patients with metabolic syndrome showed signs of activation of coagulation together with a slowdown functions of the fibrinolytic system and activation of the anticoagulation system. In young patients with hypertension without abdominal obesity increased were the levels of endothelin, plasminogen activator inhibitor type 1, angiotensin II inhibitor and extrinsic pathway of coagulation. Patients with abdominal obesity without arterial hypertension had no significant change in adipokin levels and markers of endothelial dysfunction compared to control group. Conclusion. In young patients with a variety of components of the metabolic syndrome revealed were signs of intravascular activation of blood coagulation in conjunction with the imbalance of adipokines levels and endothelial dysfunction.

Prognostic value of central aortic pressure and peripheral blood pressure in relation to the development of pre-eclampsia was assessed in pregnant women with different forms of hypertension. It was shown that development of pre-eclampsia was associated with higher mean 24-hour systolic blood pressure (BP), time index of systolic BP, variability of diastolic BP, and pulse BP measured on weeks 16-22 of gestation. Pregnant women with hypertension, especially those with pre-eclampsia were characterized by absence of proper nocturnal BP lowering or BP elevation during night hours (non-dippers and night-peakers). Critical values for prediction of preeclampsia were daily average central (aortic) systolic BP higher than 115 mm Hg and a mean daily brachial systolic BP above 131 mm Hg.

We presented evaluation indicators of insulin resistance, leptin, adiponectin, plasminogen activator inhibitor type 1 angiotensin II and endothelin in young adults aged 20-44 years with abdominal obesity and hypertension. In young patients with abdominal obesity and hypertension in comparison with the isolated hypertension and isolated abdominal obesity identified dyslipidemia, insulin resistance, adipokines disbalance with increased levels of leptin and plasminogen activator inhibitor type-1 and decreased level of adiponectin. In patients with isolated hypertension we have found laboratory signs of endothelial dysfunction with increased levels of endothelin and angiotensin II in comparison with abdominal obesity and abdominal obesity with hypertension.

В статье на основании данных проспективного наблюдения за больными, получающими терапию варфарином, проанализированы основные факторы, определяющие безопасность подбора поддерживающей дозы препарата. Выявлено, что достижение первого значения МНО ≥2,0 на 3–5-е сут. начала терапии варфарином достоверно связано с развитием чрезмерной гипокоагуляции (МНО ≥4,0). На основании оценки генотипа выявлена зависимость темпов насыщения варфарином от носительства аллельных вариантов CYP2C9 и VKORC1. Показано, что быстрые темпы достижения антикоагулянтного эффекта в подавляющем большинстве случаев связаны с носительством «неблагоприятного генотипа» (аллельных вариантов CYP2C9 *2/*2, или *3/*3, или 2/*3, или аллельного варианта АА VKORC1, или одновременного носительства двух гетерозиготных полиморфизмов CYP2C9 и VKORC1). Учитывая полученные результаты, авторами сделан вывод о высокой практической значимости проведения исследования крови на МНО на 3–5-е сут. от начала терапии. На основании проведенного дискриминантного анализа выявлен клинический предиктор развития чрезмерной гипокоагуляции, обусловленной передозировкой варфарина, — терапия амиодароном. Полученные данные легли в основу модификации существующего алгоритма подбора дозы варфарина.