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Introduction. All thrombotic microangiopathy (TMA) variants in obstetric practice have a diverse clinical presentation and can manifest as various system and organ damage, which often makes it difficult or interfere with the diagnostic assessment, thus slowing down initiation of the necessary therapy.Aim. To study the clinical presentations of various TMA variants in obstetric practice.Materials and methods. A total of 313 pregnant women were enrolled in the study, of which atypical hemolytic uremic syndrome (aHUS) was diagnosed in 71 women, “HELLP syndrome” in 124 women, and “PE” with varied severity in 70 women. A group of patients with more rare causes of TMA was also identified: TTP and sepsis in 13 patients, and 35 patients without signs of TMA were included in the control group. We assessed and compared the main clinical, laboratory and instrumental findings.Results. The study identified damage to various systems and organs in various TMA types in obstetric practice. The damage to kidneys, liver, nervous system, visual organs was observed in patients with aHUS, HELLP syndrome, TTP, septic TMA and PE, while the damage to skin, cardiovascular system and lungs was detected in patients from all groups except for PE. Small and large vessel thrombotic complications were detected in patients from the former three groups. The patients with aHUS showed the maximum multisystemic presentation severity.Conclusions. The thrombotic microangiopathy in obstetrics is generalized in nature, and various symptoms of organ dysfunction require a multidisciplinary approach to such patients.

The pathogenesis of severe coronavirus infection COVID-19 is associated with activation of immune system, cytokine storm, impaired blood clotting, microvascular thrombosis, organ ischemia and multiple organ dysfunction syndrome. The role of various lymphocyte subpopulations in COVID-19 is still debated. The aim of our study was to analyze the subpopulational profile of peripheral blood lymphocytes in COVID-19 patients as compared with healthy donors.The study included 20 COVID-19 patients (11 males and 9 females,) and 26 healthy donors. Average age of the patients was 52 and 56 years, respectively. Clinical examinations were performed by standard laboratory methods. Peripheral blood lymphocytes were isolated in the Ficoll gradient. The cells were stained with antibodies to specific antigens of main lymphocyte populations, endothelial cells, and apoptotic cell markers. The analysis was performed by flow cytometry. The results showed that all patients had elevated C-reactive protein (14- to 35-fold), ferritin (1.2- to 13-fold), D-dimers (1.2- to 90-fold). 55% of men had a decrease in the absolute number of lymphocytes, in women this index was at the low normal limit. Cytometric analysis showed that, among peripheral blood lymphocytes, the proportion of functional cells expressing the CD45 marker ranged from 2 to 12% in 70% of patients, as compared with 80-99% among the donors. The proportion of CD45+ lymphocytes significantly correlated with the level of hemoglobin, but not with the levels of inflammatory biochemical markers. Among the functional lymphocytes of patients, there was a decrease in the proportion of CD3+, CD4+, CD8+T cells, increased proportion of natural killer CD56+ and the apoptotic (AnnexinV+) cell contents, but the proportion of CD19 and HLA-DR+B cells was not changed. Analysis of the lymphocyte (LC) subpopulations that did not express CD45 marker showed that this fraction contained different lymphocyte subsets with reduced expression of CD4, CD8, CD19, CD56 etc. in the blood of patients and donors. Higher percentage of endothelial cells expressing CD62P marker made the difference between patients and donors.Laboratory determination of lymphocyte subsets in blood samples of COVID-19 patients does not reflect the real severity pattern of the disease, thus requiring studies of the CD45-expressing functional cell populations.

Introduction. Pregnancy is one of the most frequent triggers of congenital and acquired forms of thrombotic thrombocytopenic purpura (TTP).Aim — to develop tactics for the treatment of pregnant women with TTP.Results. TTP was associated with pregnancy in 55.5 % of all cases of TTP in women. In 5 pregnancies in which the diagnosis of TTP was known before pregnancy, or established in the early stages, TTP was treated throughout the pregnancy. In the congenital form, plasma transfusions were performed once every two weeks until the 20th week of pregnancy, or weekly, if thrombocytopenia < 150 × 109 /L persisted. Plasma transfusions were performed weekly after the 20th week with the goal of achieving clinical remission. With acquired TTP, glucocorticosteroids and plasma exchanges were used as treatment, in 1 case — rituximab, with the aim of achieving a clinical remission and an ADAMTS13 activity > 20 %. In this group of pregnant women, 1 caesarean section was performed and there were 4 cases of vaginal deliveries, with a total of 5 children being born with an average Apgar score of 7.5. In 7 pregnancies in which TTP fi rst manifested late, leading to a delayed diagnosis, preventive and curative measures were not carried out before delivery. In this group there were 2 abortions of pregnancy, 5 surgical deliveries, 3 cases of preeclampsia, 3 acute cerebral circulatory disorders, 1 intraabdominal bleeding, 1 case of acute renal failure, with two women undergoing mechanical ventilation. There was 1 case of antenatal fetal death, with a total of 4 children being born, who were assessed on the Apgar scale with an average of 5 points.Conclusion. Timely diagnosis as well as ongoing therapeutic and preventive measures help to avoid complications during childbirth in pregnant women with TTP.

Background: At the present moment, an urgent and unresolved problem is the search for a method to diagnose disorders of the hemostasis system in patients with the new coronavirus infection. The integral tests, in particular, the thrombodynamics test, will presumably make it possible to monitor changes in blood clotting, and predict the course of the disease in patients with COVID-19. Aims: To comparatively assess the plasma hemostasis parameters and results of the thrombodynamics test in patients with COVID-19 viral infection of different severity. Methods: The study included 96 patients with a confirmed diagnosis of COVID-19, admitted to a hospital for infectious diseases on the base of the V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology in the period from April 23, 2020, to June 20, 2020, and discharged at the end of treatment. SARS-CoV-2 was identified by PCR. The patients were stratified by the severity into 3 groups: mild course (n=25), moderate course (n=54), severe course (n=17). The diagnostics and treatment of patients were carried out in accordance with the Temporary Methodological Recommendations of the Ministry of Health of the Russian Federation for the prevention, diagnosis and treatment of the new coronavirus infection, versions 5, 6, 7. In the course of the treatment, the patients were assessed for APTT, prothrombin %, prothrombin time (PT) and thrombin time, fibrinogen, D-dimer, platelet count, and the thrombodynamic test parameters (V/Vi/Vst, Tlag, Cs, D). Results: Significant differences were observed in the thrombin time, D-dimer, platelet count, and the thrombodynamic parameters of V/Vst, Cs, and D taken before admission and a week after admission. We found a relationship between the parameters of hemostasis (fibrinogen concentration, PT, prothrombin %, APTT, Tlag, D) and the duration of hospital stay. There was a positive relationship between the content of fibrinogen and D (r=0.6307, p 0.0001) and a strong positive relationship between PT and Tlag (r=0.7499, p 0.0001). Conclusions: The thrombodynamics test can be recommended as a potential tool for a personalized approach to monitoring the hemostasis system and treating patients with COVID-19.

Materials and methods: a prospective non-randomized pilot multicenter study of the informativeness and clinical significance of hemostasis laboratory tests in 1210 patients with COVID-19 in disease course, including favorable and unfavorable outcomes, was performed Hemostasis was assessed using clotting tests and D-dimer concentration, thromboelastography (TEG) and thrombodynamics (TD) Results: comparison of COVID-19 laboratory parameters and clinical picture showed that 75% of patients have pronounced activation of the plasma coagulation system upon admission to the hospital Hypercoagulation is recorded in all tests, reaching a maximum in patients with subtotal (CT-3) and total (CT-4) lung lesion and/or resuscitation patients with a clinical picture of pulmonary embolism and unfavorable outcome Low molecular weight heparins (LMWH) in a standard dosage leads to suppression of the initial hypercoagulable syndrome in more than half of the patients (from 75 to 31%) All patients without LMWH laboratory effect developed thrombotic complications For clotting tests, insufficient sensitivity to changes in hemostasis against the background of LMWH was revealed The D-dimer test effectively correlates with the severity and outcomes of COVID-19, but is not suitable for the control of heparin therapy, which is associated with the effect of lysis of existing blood clots and the lack of response to a decrease in the coagulation activity of patients Methods of thromboelastography and thrombodynamics effectively record a decrease in the activity of the coagulation system and can be used to control heparin therapy The correlation coefficient between the methods was 0,77 The dynamic indices of D-dimers, TEG and TD in severe patients and, especially, in patients with fatal outcomes revealed the greatest sensitivity to the control of heparin therapy in the Thrombodynamics test, which allows, along with thrombosis, to record hypercoagulable states and the risk of bleeding, which are the outcome of thrombohemorrhagic syndrome in patients with COVID-19 Материалы и методы исследования: проведено проспективное открытое нерандомизированное пилотное многоцентровое исследование информативности и клинической значимости лабораторных тестов гемостаза у 1210 пациентов с COVID-19 в динамике заболевания, включая благоприятные и неблагоприятные исходы Оценку гемостаза проводили с использованием клоттинговых тестов и концентрации D-димера, тромбоэластографии (ТЭГ) и тромбодинамики (ТД) Результаты: при сопоставлении лабораторных показателей и клинической картины COVID-19 показано, что у 75% больных при поступлении в стационар наблюдается выраженная активация плазменной системы свертывания Гиперкоагуляция фиксируется по всем тестам, достигая максимума у больных с субтотальным (КТ-3) и тотальным (КТ-4) поражением легких и/или реанимационных больных с клинической картиной тромбоэмболии легочной артерии и неблагоприятным исходом Назначение низкомолекулярных гепаринов (НМГ) в стандартной дозировке приводит к подавлению исходного гиперкоагуляционного синдрома более чем у половины больных (с 75 до 31%) Все пациенты без лабораторного эффекта НМГ развили тромботические осложнения Для клоттинговых тестов выявлена недостаточная чувствительность к изменениям гемостаза на фоне НМГ Тест на D-димер эффективно коррелирует с тяжестью и исходами COVID-19, но непригоден для контроля гепаринотерапии, что связано с эффектом лизиса существующих тромбов и отсутствием ответа на снижение коагуляционной активности больных Методы ТЭГ и ТД эффективно регистрируют снижение активности свертывающей системы и могут использоваться для контроля гепаринотерапии Коэффициент корреляции между методами составил 0,77 Заключение: динамические индексы D-димеров, ТЭГ и ТД у тяжелых больных и особенно у пациентов с летальными исходами выявили наибольшую чувствительность к контролю гепаринотерапии у теста ТД, что позволяет наряду с тромбозами фиксировать гиперкоагуляционные состояния и риск кровотечений - исходы тромбогеморрагического синдрома у больных с COVID-19

Aim To investigate plasma hemostasis in patients with different levels of COVID-19 severity Materials and methods The study included 46 patients with confirmed COVID-19, who were stratified into four groups based on disease severity as mild (1), moderate (2), severe (3), and critically severe (4) Laboratory investigations included APTT, Quick's prothrombin time, concentration of D-dimer, fibrinogen, ATIII, and platelet count Results D-dimer concentration >450 ng/ml was found in 100% of patients increasing from 973 (545–1635) ng/ml in group 1 to 13513 (7627–22512) ng/ml in group 4 (p 3633 ng/ml (specificity 92 3%, sensitivity 100%, AUC 0 94, p

Background Both myocardial infarction (MI) and COVID-19 are characterized by cytokine storm in blood. Purpose The objective of this study was to compare the concentration of 39 cytokines, chemokines, and growth factors in blood sera of patients with MI, COVID-19 (COV), and healthy donors. Methods Patients' blood was collected within 1–2 days after hospitalization in the cardiovascular or COVID intensive care units. All COV patients were in a severe condition; all had increased C reactive protein, 86 and 95% had increased ferritin and D-dimers levels accordingly, 8–10 times decreased lymphocyte numbers. The analysis of the humoral factors in blood serum of MI (n=22), COV (n=23) and donors (n=27) was performed using a 39-plex cytometric analysis. Results Among all factors analyzed TGFa, IL-1b, 2, 3, 5, 9, 13, 17A were almost not detectable both in patient and donor sera. The concentrations of the other 31 humoral factors in normal sera differed significantly from 0 to 22000 pg/mL. We divided them into house-keeping factors HKF ranged from 1000 to 22000 pg/mL; sentinel innate immunity factors SIF (30–200 pg/mL), and acute phase factors APF (0–30 pg/mL). HKF were detected in all samples. Among SIF and APF IL-1a, G-CSF, IFNa2, IL-7, MIP-1a, IL-12, and IFNg were detected in 56–80% donor blood while IL-1RA, MCP-3, IL-2, 6, 10, 12, 15, FLT-3F, GM-CSF, TNF-b – only in 10–55%. At the same time all MI patients were 100% positive in all these factors showing extensive activation of blood secretome. Among low incidence APF cytokines in COV patients, percentage of IL-1RA, MCP-3, IFNa2, IL-6, 10, 15, FLT-3L negative sera decreased 3–5 times; and all sera were positive for MIP-1a and IL-12. At the same time TNF-a level decreased significantly from 0 in control to 85% of negative sera in COV patients. Summarized results are shown as the ratios of factor concentrations in MI or COV sera to normal control (Fig). Blood secretome of MI changed more significantly than of COV patients. The major factors (shown in red) in MI were IL-6, IL-12, IFNg, FLT-3L, GM-CSF, and IL-15, which increased 12, 9, 6, 6, 6, and 5 times accordingly. In COV sera IL-6, IL-10, IP-10, and MCP-3 increased by 28, 12, 10, and 9 times accordingly. Less expressed however significant increases are marked with asterisks. Conclusions Acute MI is characterized by severe disturbances in blood secretome with an increased level of 25 out of 39 factors studied. Contrary to it, in COV patients the levels of IL-6, 10, IP-10, and MCP-3 were more enhanced while only 15 out of 31 exceeded normal levels. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Public Institution

Introduction: The incidence of venous thromboembolism (VTE) after cesarean section is up to 0.6%, and the widespread use of cesarean section draws attention to this group. The dosage and duration of low-molecular-weight heparin (LMWH) prophylaxis after delivery is estimated by anamnestic risk-scales; however, the predictive potency for an individual patient’s risk can be low. Laboratory hemostasis assays are expected to solve this problem. The aim of this study was to estimate the potency of tests to reflect the coagulation state of patients receiving LMWH in the early postpartum period. Materials and methods: We conducted an observational study on 97 women undergoing cesarean section. Standard coagulation tests (Fg, APTT, prothrombin, D-dimer), an anti-Xa assay, rotation thromboelastometry and thrombodynamics/thrombodynamics-4D were performed. Coagulation assay parameters were compared in groups formed in the presence or absence of LMWH to estimate the laboratory assays’ sensitivity to anticoagulation. Results: Coagulation assays revealed hypercoagulation after delivery and a tendency toward normalization of coagulation during early postpartum. The thromboprophylaxis results revealed a higher percentage of coagulation parameters within the normal range in the LMWH group. Conclusion: This research is potentially beneficial for the application of thrombodynamics and thrombodynamics-4D in monitoring coagulation among patients with high VTE risk who receive thromboprophylaxis with heparin.

Postoperative cognitive dysfunction (POCD) is a disorder that develops in the early postoperative period, persisting for several days or weeks and leading to decrease in higher cortical functions (speech, memory, attention, etc.). POCD is often associated with anesthetic techniques and drugs. This paper studied the effect of general, neuraxial and combined anesthesia on POCD development in elderly women undergoing gynecological surgery. The study featured 43 patients (mean age 65,0 ± 2.2 years). There were 12 women in the general anesthesia group, 23 in the neuraxial anesthesia group, and 8 women in the combined anesthesia group. Intraoperative monitoring included electrocardiography, non-invasive blood pressure measurement, determination of blood oxygen saturation level (rSO2) and determination of bispectral index (BIS monitoring). A day before surgery and on the 5th day after the surgery, neuropsychological tests were carried out through tracking test, Mini-Mental State Examination and frontal assessment battery. All intraoperative indicators were normal in all the patients. POCD was diagnosed in 3 women who were under general anesthesia, in 7 women under neuraxial anesthesia and 2 under the combined group (25, 30 and 25 % relative to the total number of patients in the groups, respectively). The average rSO2 value was below the initial level in all groups: below by 6 % in the general anesthesia group, by 15 % in the neuraxial group, and by 10 % in the combined group. However, the differences were statistically insignificant (p >0.05). The study found no relationship between anesthetic techniques and POCD., Послеоперационная когнитивная дисфункция (ПОКД) — расстройство, развивающееся в ранний послеоперационный период, сохраняющееся в течение нескольких дней или недель и проявляющееся снижением высших корковых функций (речи, памяти, внимания и др.). Возникновение ПОКД часто связывают с методом анестезиологического обеспечения и препаратами. В работе изучено влияние общей, нейроаксиальной и сочетанной анестезии на развитие ПОКД у женщин пожилого и старческого возраста при операциях в гинекологии. В исследование включили 43 пациентки (средний возраст — 65,0 ± 2,2 года). В группе с общей анестезией было 12 женщин, с нейроаксиальной — 23, с сочетанной — 8. Интраоперационный мониторинг включал снятие электрокардиограммы, неинвазивное измерение артериального давления, определение уровня насыщения крови кислородом (rSO2), определение биспектрального индекса (BIS-мониторинг). За день до операции и на 5-й день после нее проводили нейропсихологическое тестирование с помощью теста слежения, краткой шкалы оценки психического статуса и батареи оценки лобной функции. Все интраоперационные показатели у всех пациенток были в норме. ПОКД была диагностирована у 3 женщин, находившихся под общей анестезией, у 7 — под нейроаксиальной и у 2 — под сочетанной (25, 30 и 25 % относительно общего числа пациенток в группах соответственно). Среднее значение показателя rSO2 во всех группах было ниже исходного уровня: при общей анестезии — на 6 %, при нейроаксиальной — на 15 %, при сочетанной — на 10 %, однако различия были статистически незначимыми (p >0,05). Связь между типом анестезии и развитием ПОКД не была выявлена.

The article deals with regional anaesthesia peculiarities in womnen wiith morbid obesity in obstetrics and gynecology. The articles discusses cases demonstating safety and effectiveness of low-dose comnbined spinal-epidural anaesthesia in these patients.

Results of prospective randomized comparative research of 2 total hemoglobin estimation methods are presented. There were laboratory tests and continuous noninvasive technique with multiwave spectrophotometry on the Masimo Rainbow SET. Research was carried out in two stages. At the 1st stage (gynecology)--67 patients were included and in second stage (obstetrics)--44 patients during and after Cesarean section. The standard deviation of noninvasive total hemoglobin estimation from absolute values (invasive) was 7.2 and 4.1%, an standard deviation in a sample--5.2 and 2.7 % in gynecologic operations and surgical delivery respectively, that confirms lack of reliable indicators differences. The method of continuous noninvasive total hemoglobin estimation with multiwave spectrophotometry on the Masimo Rainbow SET technology can be recommended for use in obstetrics and gynecology.