Background: At the moment, an urgent and unresolved problem is the search for a diagnostic method for disorders of the hemostasis system in patients against the background of the course of a new coronavirus infection. Presumably, integral tests, in particular, the thrombodynamics test, will make it possible to monitor changes in blood clotting, predict the course of the disease in patients with COVID-19. Aims: to comparative assessment of plasma hemostasis parameters and thrombodynamics test in patients with COVID-19 viral infection of varying severity. Methods: The study included 96 patients with a confirmed diagnosis of COVID-19, hospitalized in an infectious diseases hospital on the basis of National Medical Research Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakov in the period from 04.23.2020 to 06.20.2020 and discharged at the end of treatment. SARS-CoV-2 was identified by PCR. Patients were stratified by severity into 3 groups: mild course (n = 25), moderate course (n = 54), severe course (n = 17). Diagnostics and treatment of patients was 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 new coronavirus infection, versions 5, 6, 7. In the dynamics of treatment, patients were assessed APTT, prothrombin %, prothrombin time and thrombin time, fibrinogen, D-dimer, platelet count and thrombodynamic test (V / Vi / Vst, Tlag, Cs, D). Results: It was found that significant differences before admission and a week after the start of hospital treatment were observed for the thrombin time, D-dimer, platelet count, and thrombodynamic parameters: V / Vst, Cs, D. PT, APTT, TD (Tlag, D)) with 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.

COVID-19, a severe acute respiratory syndrome caused by SARS-CoV-2, may predispose to thrombotic events, especially when combined with antiphospholipid antibodies (aPL). However, there are limited data on prevalence and antigenic specificity of aPL in COVID-19. Complement activation is assumed to play an important role in pathogenesis of COVID-19-associated coagulopathy. During the SARS-CoV-2 pandemic, it is necessary to identify important biomarkers for predicting severe course of COVID-19 and risk of thrombotic complications. Our objective was to evaluate the aPL profile, quantitative content and activity of complement and its components in COVID-19 patients graded by severity in the course of time. IgM and IgG antibodies to cardiolipin (CL), phosphatidylserine (PS), β2-glycoprotein-I (β2-GP-I), prothrombin (PT), annexin V (An V), as well as C1q complement component, content of its C3 and C4 components and total complement activity were determined in blood serum using ELISA approach. 141 patients with COVID-19 were included in the study. Group 1 consisted of 39 patients with mild form, group 2 (65 patients) presented with moderate form, and group 3 included 37 patients with severe form of COVID-19. Blood samples were obtained on day 3-7 of the disease (1st point) and after 14-28 days (2nd point). The results were as follows: aPL were detected in 29.1% of the total COVID-19 cohort, frequency of aPL detection by the severity grade did not differ (33.3%, 24.6% and 32.4%). In 8.5% of the patients, aPL were detected only at the 1st time point; in 14.2%, only at the 2nd point; and in 6.4% of the cases, at the both time points. Antibodies to PT (16.3%) and An V (11.3%) were revealed more frequently. The detection frequency of antibodies to PT was significantly higher than antibodies to CL and PS (7.1%), β2-GP-I (7.8%). The prevalence of aPL in groups 1 and 3 did not differ. At the 1st point in group 3, increased levels of C4 (89.2%) and C3 (24.3%) in blood, and a decrease in complement activity (35.1%) were more often observed than in group 1. At the 2nd time point in group 3, a decrease in complement activity was often detected (59.5%). The C3 levels exceeding 720 μg/ml were found to predict a 2.6-fold increased risk of severe COVID-19, and this risk became 3.3 times higher at C4 levels of > 740 μg/ml. The antibodies to PT and An V are often detected in COVID-19 patients, along with low prevalence of antibodies to CL and β2-GP-I. These antibodies can be involved in pathogenesis of COVID-19-associated coagulopathy, being detectable at the late stage of the disease, and they may trigger APS in predisposed patients and reconvalescents. Although presence of aPL antibodies is not associated with COVID-19 severity, their persistence over the period of convalescence may be an additional risk factor for thromboembolic complications. The COVID-19 patients are characterized by activation of the complement system, which increases in severe cases, and manifests with increased or decreased levels of C3 complement component, increased levels of C4 component in blood, and a decreased total complement activity. Quantitative determination of C3 and C4 complement components over the period of COVID-19 progression is of prognostic value, with respect to severity of the disease.

The aim of the work was to determine frequency of lupus anticoagulant (LA) detection in patients at various degrees of COVID-19 severity as well as duration of LA circulation after the infectious disease. The study included 103 patients with COVID-19. The patients were observed during the hospital care and in ambulance, if required. The patients were admitted to the departments of infectious diseases arranged at the V.I.Kulakov National Medical Research Center for Obstetrics, Gynecology, and F.I. Inozemtsev City Clinical Hospital. Treatment schedules and stratification of the patients by clinical severity was carried out in accordance with Interim Guidelines issued by the Ministry of Health of the Russian Federation for the prevention, diagnosis and treatment of new coronavirus infection (version 9). The following groups were formed: mild (n = 27), moderate (n = 55) and severe (n = 20). The patients were tested for LA positivity in the course of disease: on the day of starting medical care (with outpatient observation), or on the day of hospitalization; repeated tests were made before discharge (inpatients), and later, 1-2 months and 7 months after recovery. Lupus anticoagulant was determined by two independent tests (dRVVT and SCT), i.e., as a screening test and a confirmation test. At initial examination, LA was found in 50 patients (49%). The effect of LA in 98% of cases was observed with dRVVT test, as an increase of normalized ratio (NR). The maximum median value of NR was 1.54 (0.97: 2.1) was revealed in patients with severe course of COVID-19 (p 0.0001) compared with other groups and correlated with severity of the infectious process (r = 0.491, p 0.0001). In mild cases of COVID-19, LA was detected less often (4 cases, 14.8%) than in moderate severity cases (27, 49.1%), and severe patients (19, 95%) (p 0.05). Re-examinations of the patients before discharge from the hospital and 1-2 months later revealed high frequency of LA (p 0.05). However, no LA-positive test was found 7 months after discharge. In patients with COVID-19, high frequency of circulating LA was registered, depending on severity of the infectious process. In addition, we have first shown that persistence of the circulating LA over post-infectious period does not exceed 7 months.

Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии им. академика В.И. Кулакова; 117997, Россия, Москва, ул. Академика Опарина, д. 4 Резюме Введение. Ведение беременных с аномальной инвазией плаценты требует мультидисциплинарного подхода, включая оптимизацию анестезиологического обеспечения и хирургических подходов, применение технологий кровесбережения, наличие современных гемостатических препаратов, ингибиторов фибринолиза, доступности компонентов крови, лабораторной поддержки, предотвращение коагулопатии и оптимизацию послеоперационной анальгезии. Цель исследования. Оптимизация трансфузиологического обеспечения абдоминального родоразрешения беременных группы риска по развитию акушерских кровотечений путем контролируемой коррекции нарушений системы гемостаза. Материалы исследования. Группу исследования составили 24 женщины с аномальной инвазией плаценты (АИП) и кровотечением во время кесарева сечения в возрасте от 23 до 47 лет на сроке беременности от 32 до 36 нед. Первую группу составили 14 пациенток-в составе комплексной терапии вводилась транексамовая кислота; вторую группу-10 женщин, которым в составе комплексной терапии вводилась аминометилбензойная кислота. Результаты. У всех пациенток использована аппаратная реинфузии аутоэритроцитов. Трем пациенткам первой группы (21,4%) при рефрактерном кровотечении был введен рекомбинантный VIIа-фактор свертывания (Коагил-VII, Россия) в дозе 60 мкг/кг массы (средняя доза 6,6 ± 1,4 мг), отмечено уменьшение кровотечения, операция закончена в объеме метропластики. Восьми пациенткам на начальном этапе развития кровотечения до введения свежезамороженной плазмы (СЗП) вводился концентрат протромбинового комплекса 600-1 200 ЕД, что позволило сократить объемы донорской СЗП у этих пациенток. При исследовании гемостаза выявлена обратная связь очень высокой силы между объемом кровопотери и уровнем фибриногена в группах пациенток. Заключение. Применение фактора VIIа при рефрактерном массивном акушерском кровотечении (МАК) у пациенток с АИП позволяет сократить объем кровопотери, выполнить метропластику и сохранить фертильность женщины. Менеджмент крови пациента (МКП) у беременных с АИП позволяет реализовать органосохраняющую тактику у 91,7% женщин.

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