Coagulopathy in COVID-19 patients is presumably based on systemic hypercoagulation with the inflammatory response. As a result of endothelial dysfunction, tissue factor and von Willebrand factor (vWF) are released into the blood stream, which leads to prothrombinase activation. The vWF/ADAMTS-13 ratio can be used for monitoring the severity of the disease. This observational prospective study included 141 patients with COVID-19. In patients with mild COVID-19 (group 1), the assessment was performed on the 3rd–7th day of illness (point 1) and 14–28 days after recovery (point 2). In patients with moderate (groups 2) and severe (group 3) COVID-19, the assessment was performed during hospitalization (point 1) and after 14 days (point 2). The vWF:RCo/ADAMTS-13:activity (point 1), vWF/ADAMTS-13 (point 2) and vWF:RCo/ADAMTS-13:activity (point 2) ratios were significantly higher in patients with moderate and severe COVID-19. Moreover, in these patients, both ratios increased after recovery (point 2), which is a negative prognostic factor of thrombotic complications. Thus, COVID-19 is characterized by a decrease in the concentration and activity of ADAMTS-13 metalloproteinase, especially in patients with the severe form of COVID-19. A decrease in ADAMTS-13 activity results in an increase in vWF concentration and activity so the ratio of vWF to ADAMTS-13 changes significantly.

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.

Трансфузиологическое обеспечение абдоминального родоразрешения у беременных высокого риска развития кровотечения при контроле гемостаза

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.

SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2) activates the immune system, causing thrombin dysregulation and tissue damage and reduces endothelium anticoagulant function, leading to excessive thrombin formation. Hypercoagulability, which causes multiple organ failure in critically ill COVID-19 (COronaVIrus Disease 2019) patients, can be detected by viscoelastic tests like thromboelastography and rotational thromboelastometry (ROTEM). We aimed to assess the coagulation system status and fibrinolytic activity using ROTEM thromboelastometry in patients with COVID-19 and convalescents. The observational prospective study included 141 patients with COVID-19: Group 1—patients with mild (n = 39), Group 2—patients with moderate (n = 65), and Group 3—patients with severe (n = 37) COVID-19. The coagulation status was assessed twice—during the disease and in convalescence. The male gender, age > 56 years, overweight, and obesity were risk factors for developing severe COVID-19. During the disease in patients with moderate and severe COVID-19, the hemostatic system was characterized by a procoagulant status, which persists during the period of convalescence. Fibrinolysis shutdown was detected in both moderate and severe patients with COVID-19. The procoagulant status of the coagulation system and the shutdown of fibrinolysis are typical for patients with moderate to severe COVID-19. In convalescents, activation of coagulation remains, which indicates the need to monitor the hemostatic system after Illness.

Introduction. Endogenous heparin-like syndrome (HLS) in obstetrics is a rare complication characterized by the manifestation of the effect of heparin in the absence of its exogenous administration due to an increase in the concentration of glycosaminoglycans (GAG). Obstetric patients with HLS are at risk for the development of hemorrhagic complications in the perioperative period. The heterogeneity of the structure and anticoagulant activity of GAG complicates the laboratory diagnosis and therapy of HLS.The objective was to conduct a retrospective analysis of clinical observations of endogenous heparin-like syndrome in patients from an obstetric hospital and literature data on the diagnosis and therapy of hemorrhagic syndrome associated with HLS.Materials and methods. The retrospective analysis included 6 obstetric female patients treated on the basis of the Academician V. I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, with laboratory signs of endogenous heparin-like syndrome (HLS).Results. Laboratory signs of HLS were detected in women after uterotomy, 5 had additional risk factors (thrombotic microangiopathy (TMA), placental abruption, preeclampsia, surgical correction of fetal spina bifida. The use of thromboelastometry, namely HEPTEM, made it possible to identify HLS. The bleeding was stopped after the administration of antifibrinolytic in observations № 2–5, however, the bleeding recurred in the woman in observation № 6 because non-specific therapy did not fully normalize thrombin generation, which was reduced under the influence of GAG.Conclusion. A clinically significant increase of endogenous GAG in the blood is a complex process. Female patients have high risk of bleeding associated with HLS need to laboratory monitoring of the hemostasis system in the perioperative period. Different laboratory methods, especially, tests with heparinase should be used to increase the probability of detecting HLS. TEM parameters allow for reasonable hemostatic therapy.