EDITORIAL
The rate of thrombosis and disseminated intravascular coagulation (DIC) has been increasing in COVID-19 patients. Key features related to such condition include minimal or no risk of bleeding, moderate thrombocytopenia, high plasma fibrinogen as well as complement components level in the areas of thrombotic microangiopathy. The clinical picture is not typical for classic DIC. This review systematizes the pathogenetic mechanisms of hypercoagulation in sepsis and its extreme forms in patients with COVID-19. The latter consist of the thrombosis-related immune mechanisms, the complement activation, the macrophage activation syndrome, the formation of antiphospholipid antibodies, the hyperferritinemia, and the dysregulation of the renin-angiotensin system. Taking into consideration the pathogenetic mechanisms, the biomarkers had been identified related to the prognosis of the disease development. Patients with pre-existing cardiovascular disease and other risk factors, including obesity, diabetes, hypertension, and aging pose the peak risk of dying from COVID-19. We also summarize new data on platelet and endothelial dysfunction, immunothrombosis, and, as a result, thrombotic storm as essential components of COVID-19 severe features.
ОRIGINAL ARTICLES
Aim: to evaluate an impact of menopausal hormone therapy (MHT) on late postmenopausal multimorbid women’s quality of life (QoL).
Materials and Methods. 132 late postmenopausal women were enrolled to the study and were divided into two groups: group 1 consisted of 66 subjects with moderate multimorbidity and Charlson Comorbidity Index (CCI) < 3; group 2 (66 patients) had high multimorbidity (CCI ≥ 3). Women receiving or not MHT were subdivided in both groups. SF-36 questionnaire was used to assess QoL, Hospital Anxiety and Depression scale (HADS) – for evaluating emotional status, MMSE test (Mini-Mental State Examination) – for cognition evaluation. Modified Menopausal Index (MMI) was calculated as well.
Results. Women with a low level of comorbidity who had previously received MHT have a significantly higher QoL. The median age for subjects was 69 [65; 71] years, median CCI score was 3.5 [2.5; 5.0]. In addition, in group 2 there were found significantly lower physical functioning (p < 0.001), role-physical functioning (p = 0.028), physical health (p = 0.002) domains, as well as more severe persistent menopausal symptoms (p = 0.011) and depression (p = 0.043). History of MHT in group 1 was associated with higher levels of physical functioning (p = 0.033) and role-physical functioning (p = 0.023), whereas in group 2 MHT was associated with better cognition (p = 0.028) and lower depression symptoms compared with those lacking history of MHT.
Conclusion. Multimorbidity in late postmenopausal women was associated with impaired QoL physical domains. MHT allows to effectively improve QoL in women with moderate multimorbidity and to protect cognitive state to higher level as well as reduce depression symptoms in women with severe multimorbidity.
Introduction. Here we discuss the problem of timely diagnostics and prevention of Rh-immunization of pregnant women as well as fetal hemolytic disease, which remains currently relevant, despite the existence of proven diagnostic, therapeutic and preventive methods.
Aim: to assess the medico-economic efficiency of non-invasive prenatal diagnostics of using fetal Rh factor (rhesus D antigen, RhD) in maternal blood – a fetal RhD-genotyping.
Materials and Methods. A retrospective observational study was conducted to analyze determining fetal Rh-factor in the blood samples from 4109 Rh-negative pregnant women observed in the 41 medical facilities of the Ulyanovsk region in the years 2018–2020. The fetal RhD level was determined by polymerase chain reaction at gestational age of ≥ 10 weeks. To assess testrelated medical effectiveness, there were examined sensitivity, specificity, predictive value of positive and negative data as well as diagnostic accuracy. The data collected during the study were compared with those obtained after delivery. To assess the economic efficiency, the difference between the cost of immunization and the cost of determining the fetal Rh factor level was determined.
Results. A positive and negative fetal Rh-factor was detected in 67.26 % (n = 2793) and 32.74 % (n = 1316) cases, respectively. Diagnostic accuracy of the test system "Test-RhD" was 99.40 %, sensitivity – 99.84 %, specificity – 97.51 %, the prognostic value of a positive result was 99.43 %, the predictive value of a negative result – 99.28 % with low rate of false positive and false negative data. It was shown that our study allows to avoid unnecessary immunization costs for all Rh-negative pregnant women.
Conclusion. Analysis of the diagnostic characteristics and cost-effectiveness of the RhD test evidences about high medical significance of the method described and allows to recommend its wider application.
Introduction. Currently, a shortage of studies demonstrating the relationship between body composition disorders in men with excess adipose tissue and metabolic syndrome (MS), depending on the level of testosterone, estradiol, sex hormone binding globulin (SHBG), anthropometric parameters, or blood pressure (BP) has been noted.
Aim: to examine a relationship between disturbed anthropometric parameters, level of sex hormones and BP in men with MS.
Materials and Methods. There were enrolled 64 overweight men to the study. The patients were divided into 3 groups based on the body mass index (BMI): group 1 – with overweight (n = 24), group 2 – with the first degree of obesity (n = 21), group 3 – with the second and third degree of obesity (n = 19). A correlation analysis was carried out between the data of bioimpedance analysis (BIA) and laboratory data, as well as additionally assessing the level of inter-group difference.
Results. Our study allowed to find the relationship between the parameters of body composition in men with overdeveloped adipose tissue and MS that was coupled to the level of testosterone, estradiol, SHBG, anthropometric parameters as well as blood pressure indicators. A moderate negative correlation was observed across entire patient sample between the testosterone level and several anthropometric parameters: waist circumference (WC), WC/hip circumference and BMI (p < 0.05). A weak negative correlation was found between the level of testosterone, fat mass (FM) and the proportion of FM in the general sample. A weak negative correlation between systolic BP and testosterone level throughout the patient sample was found, but a moderate negative correlation was observed solely in group 3. A positive weak correlation was found between testosterone and estradiol level in the general sample as well as in group 2, whereas in group 1 it was moderate. In contrast, in group 3 such a correlation was negative and weak. A positive correlation can be also traced between testosterone and SHBG level particularly being moderate in the entire sample as well as in groups 1 and 2, and noticeable in group 3.
Conclusion. The relationship was revealed between the parameters of body composition in men with excessive adipose tissue and MS related to testosterone, estradiol, SHBG level as well as anthropometric parameters and ВР corroborating systematic and multi-layered nature underlying obesity.
Introduction. Retrochorial hematoma (RH) often detected during routine ultrasound examination represents one of the multiple causes resulting in early pregnancy loss. RH results from the detachment of the chorionic plate from the vertebrae of the uterine decidual membrane and may lead to complicated course of pregnancy.
Aim: to develop a differential approach to diagnose and manage pregnancy with RH.
Materials and Methods. A prospective open-ended interventional non-randomized study was conducted by enrolling 170 women. The main group consisted of 85 pregnant women with RH, which were divided into 2 groups: group I (n = 45) – patients with RH and burdened obstetric history; and group II (n = 40) – pregnant women with RH without a history of obstetric complications. The control group included 85 women with uncomplicated pregnancy. The incidence of hereditary thrombophilia was assessed by measuring rate of high thrombogenic risk mutations in the genes of factor (F) V Leiden and prothrombin (FII) G20210A; blood levels of lupus anticoagulant (LA) and anti-cardiolipin antibodies (aCL), β2-glycoprotein 1 (β2-GP1), annexin V and prothrombin; ADAMTS-13; rate of low thrombogenic risk polymorphisms, prevalence and spectrum of bacterial-viral infections.
Results. It was revealed that women with RH had occasional genetic and acquired hemostasis defects as well as impaired florocenosis of the urogenital tract. Defects in the fibrinolysis system prevailed among the hereditary hemostasis defects: 75.5 % in group I, 32.2 % in group II, and 4.7 % in the control group. No decrease in the activity of natural anticoagulants – antithrombin and protein C was found. Among the acquired thrombophilic conditions, a large proportion of circulating antiphospholipid antibodies (APA) was found: 46.6 % in group I, 27.5 % in group II, and 2.3 % in the control group. Cervicitis of nonspecific etiology prevailed among dysbiosis signs: 53.3 % in group I, 47.5 % in group II and 11.7 % in the control group.
Conclusion. RG formation is a multifactorial process, which pathogenesis involves both genetic and acquired factors such as APA, especially in combination with genetic thrombophilia (FV Leiden and FII G20210A), as well as inflammatory or pro-inflammatory status. We consider that all patients with RG as well as those with former RG are indicated to undergo the above-mentioned studies. It is advisable to include tranexamic acid, progesterone, low molecular weight heparins and antibiotics in the therapy regimen if indicated.
REVIEW ARTICLES
After the vaccination campaign initiation in Europe and the UK, reports of rare cases of atypical thrombosis, including sinus vein thrombosis and splanchnic venous thrombosis, began to appear in association with the use of vector vaccines AstraZeneca (ChAdOx1) and Johnson & Johnson/Janssen. The syndrome called VITT (vaccine-induced immune thrombotic thrombocytopenia) manifested as thrombosis simultaneously with a decrease in platelet count, a significant increase in D-dimer levels and a detection of factor 4 platelet (PF4) antibodies. We present a detailed review of the epidemiology, pathogenesis, clinical presentation, diagnostics and treatment of VITT, which is by its nature an immune complication, similar to the processes occurring in heparin-induced thrombocytopenia (HIT). All international and national organizations and regulatory authorities, including experts in the field of thrombosis and hemostasis and the VITT expert council recommend continuing the prompt mass vaccination against COVID-19 as the only method that can reduce the incidence of severe cases, stop the spread of COVID-19 infection and the emergence of new dangerous mutations in the viral genome. Failure to vaccinate poses an incomparably greater risk of fatal thrombotic and inflammatory complications associated with infections, compared with the risks of extremely rare adverse events that can occur after vaccination. It should be noted that information on VITT, described as a sporadic phenomenon of an abnormal immune response to some variants of vaccines against COVID-19, cannot be translated to other vaccines (including registered in the Russian Federation) and even more cannot be a reason for refusal to use them.
The strategy for preserving reproductive potential in the Russian Federation is focused on the personalized women’s health care and based on preclinical identification of gynecological diseases and major obstetric syndromes at the stage of predicting adverse outcomes and subsequent preventive measures able to reduce maternal and perinatal morbidity and mortality, decrease women and neonatal disability as well as profoundly reduce extremely high costs on care of premature infants. The search for effective
predictive methods of preeclampsia (PE) at the stage of preconception and in the first trimester of pregnancy is driven by the desire to identify women at greater risk of developing hypertensive disorders in order to take the necessary effective measures for
preventing placental pathology as early as possible, thereby preventing or reducing incidence rate of PE. At the same time, identifying a group of high-risk women would allow to rationally plan prenatal care, timely recognize emergence of multiple organ
dysfunction and immediately begin pathogenetic and symptomatic therapy. Taking into account the national and global experience of using predictive analytics software proving their success in reproductive medicine, it is reasonable to assume that converting prognosis into digital format by using artificial intelligence (AI) algorithms will open new opportunities for increasing accuracy of individual risk calculation for PE by meeting current paradigm of personalized preventive medicine. Our scientific review on domestic and international publications aims to inform a wide range of obstetricians-gynecologists about advances in AI technologies as well as prospects for machine learning to predict PE.
Introduction. The mucociliary apparatus (MCA) of the fallopian tubes (MTр) represents one of the key mechanisms and arms in functioning of female reproductive system. A prominent role of impaired MCA in the pathogenesis of reproductive system diseases and infertility, on the one hand, as well as insufficient knowledge and elucidation of this topic, on the other hand, spurred current study.
Aim: to improve our understanding about a role for reproductive system MCA and its impairment in developing diseases and infertility, as well as to identify potential perspectives for their correction.
Materials and Methods. We searched for publications and analyzed literature data from 1980 to 2020 using various scientific databases, including Index Medicus, PubMed/MEDLINE, Embase, Cochrane Library and Russian scholarly journals related to gynecology, obstetrics and reproduction.
Results. The analysis conducted allowed to originally assess the morpho-functional, structural-genetic features and other important aspects of MCA MTр. In addition, we demonstrated an impact of various factors on developing diverse types of pathological processes, including those capable of causing infertility. Moreover, we also elucidated a state of MCA MTр coupled to various diseases, including genetically determined disorders.
Conclusion. The role of impaired MCA MTр in developing pathological process and infertility was of tremendous importance and deserves close attention, because they are often remained undiagnosed by standard methods and require use of morphological and functional research methods for verification. Perspectives for diagnostics and correction of MCA MTр disorders are further discussed.
Introduction. Venous thromboembolism (VTE) is one of the lead causes for maternal mortality and morbidity during pregnancy in the majority of developed countries. The incidence rate of VTE per pregnancy-year increases during pregnancy and postpartum period about by 4-fold and at least 14-fold, respectively.
Aim: to analyze and summarize current view on risk factors of thrombotic events during gestation and to discuss recent guidelines for the management of venous thromboembolic complications during pregnancy and postpartum, by taking into account a balance between risks and benefits of using anticoagulants.
Materials and Methods. The literature search covering the last 10 years was carried out in the electronic scientific databases RSCI, PubMed/MEDLINE, and Embase. While formulating a search strategy for evidence-based information, the PICO method (P = Patient; I = Intervention; C = Comparison; O = Outcome) and the key terms “venous thromboembolism” and “pregnancy” were used.
Results. Risk factors were found to include a personal history of VTE, verified inherited or acquired thrombophilia, a family history of VTE and general medical conditions, such as immobilization, overweight, varicose veins, some hematological diseases and autoimmune disorders. VTE is considered being potentially preventable upon prophylactic administration of anticoagulants, but no high confidence randomized clinical trials comparing diverse strategies of thromboprophylaxis in pregnant women have been proposed so far. Because heparins do not cross the placenta, weight-adjusted therapeutic-dose low molecular weight heparins (LMWH) represent the anticoagulant treatment of choice for VTE during pregnancy. Once- and twice-daily dosing regimens are acceptable. However, no evidence suggesting benefits for measurement of factor Xa activities and consecutive LMWH dose adjustments to improve clinical outcomes are available. In case of uncomplicated pregnancy-related VTE, no routine administration of vitamin K antagonists, direct thrombin or factor Xa inhibitors, fondaparinux, or danaparoid is recommended. Lactating women may switch from applying LMWH to warfarin. Anticoagulation therapy should be continued for 6 weeks postpartum with total duration lasting at least for 3 months.
Conclusion. VTE is a challenging task in pregnant women expecting to apply a multi-faceted approach for its efficient solution by taking into account updated recommendations and personalized patient-oriented features.
CLINICAL CASE
Aggressive pelvic angiomyxoma belongs to one of the rare types of mesenchymal pelvic tumors found in premenopause patients. Currently, this pathology is mainly treated via surgical intervention. Alternatively, it may also be managed by using radiation or hormone therapy. The final diagnosis is usually established by histological examination of removed tumor, because biopsy analysis during examination may not always provide a high diagnostic value. This tumor type is able to relapse, even after 100 % surgically removed intervention. Immunohistochemistry examination reveals expression of progesterone and estrogen receptors. One of the hormone therapy options with good long-term effect is based on using gonadotropin-releasing hormone drugs. Taking into consideration slow tumor growth and hormonal sensitivity, one of the options for managing disease relapse is patient follow-up, especially in perimenopausal subjects. Single clinical cases have been published related to pelvic angiomyxoma so that it results in introducing individualized management for every certain patient, but unified therapeutic approaches have not been developed yet.
LECTURE
Pregnancy is a hypercoagulable state due to pro-hemostatic changes in the activity of coagulation factors and fibrinolysis and due to progressively increasing pressure on the iliac veins from the growing uterus. Thus, it is not surprising that there is an increased risk for thrombotic events and especially in the pelvic veins. With the trauma of delivery, and particularly caesarian section, the risk is accentuated in the early days postpartum. Multiparity seems to be another risk factor, which may be due to the older age of the patient. The epidemiology, risk factors, diagnosis, management and prognosis of iliac, ovarian and uterine vein thrombosis will be reviewed here, with emphasis on the relation to pregnancy.
FROM HISTORY
The article highlights historic aspects of medical and research work of the hematologist Eric Adolf von Willebrand by describing his contribution to investigating blood coagulation issues.

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