Aim. To assess the role of thromboinflammation (NETosis) and disturbances in the ADAMTS-13/von Willebrand factor (VWF) axis in the pathogenesis of hypercoagulability and their dynamics during anticancer therapy in patients with gynecological malignancies. Methods. A prospective non-randomized controlled study included 262 patients with endometrial, ovarian, cervical, and breast cancer (TNM stages I-III) and 50 healthy women (control group). We evaluated the dynamics of NETosis markers (citrullinated histone H3, myeloperoxidase – MPO), parameters of the ADAMTS-13/VWF axis, markers of hemostatic activation (D-dimer, thrombin-antithrombin complexes – TAT), interleukin-8 (IL-8), and antiphospholipid antibodies. Blood samples were collected before treatment, as well as 14 days after surgery or after the 2nd, 4th, and 6th cycles of chemotherapy (CT). Results. Prior to treatment, showed a significant increase in NETosis markers (citH3: 1.78±1.03 vs 0.33±0.13 ng/mL, p

Introduction. An imbalance between von Willebrand factor (VWF) and its primary protease, ADAMTS-13, plays a crucial role in the pathogenesis of microthrombosis and endotheliopathy. The aim of this work was to study the functioning of the ADAMTS-13/VWF axis and its interaction with thromboinflammatory reactions (NETosis) in oncogynecological patients undergoing antitumor therapy. Methods. The study included 262 patients (cancer of the endometrium, ovaries, cervix, and breast). The concentration of VWF, the antigen concentration and activity of ADAMTS-13, its inhibitor levels, NETosis markers (CitH3, MPO), and hemostasis activation markers were determined dynamically (before and after surgical treatment/chemotherapy). Results. Oncogynecological patients exhibited a significant increase in VWF concentration and a decrease in ADAMTS-13 concentration/activity (p

Cancer-associated thrombosis (CAT) is defined as venous or arterial thrombotic events occurring in patients with active malignancy or during anticancer treatment, most commonly presenting as venous thromboembolism and representing a leading cause of morbidity and mortality in oncology. Hormone-sensitive malignancies, including breast, ovarian, and endometrial cancers, are characterized by a complex interaction among tumor biology, endocrine signaling, inflammation, endothelial dysfunction, and coagulation activation. In these malignancies, venous thromboembolism (VTE) risk is influenced not only by intrinsic tumor-related mechanisms but also by patient-specific factors and anticancer therapies, particularly endocrine treatments, chemotherapy, targeted agents, and extensive surgical procedures. Breast cancer is generally associated with an intermediate thrombotic risk, although endocrine therapy—especially tamoxifen—significantly increases VTE incidence. Ovarian cancer represents one of the most thrombogenic solid tumors because of elevated tissue factor expression, inflammatory activation, advanced-stage presentation, and aggressive multimodal treatment strategies. Endometrial cancer exhibits a strong association with obesity, metabolic syndrome, prolonged estrogen exposure, and perioperative thrombotic complications. Emerging evidence highlights the role of immune-thrombosis, extracellular vesicles, inflammatory cytokines, and sex-specific coagulation pathways in cancer-associated hypercoagulability. Current guidelines increasingly support individualized thromboprophylaxis based on tumor biology, patient-specific risk factors, and bleeding risk assessment. This review summarizes the biological mechanisms linking hormones and thrombosis in breast and gynecologic cancers, discusses current evidence regarding VTE risk factors and treatment-related thrombotic complications, and explores modern approaches to biomarkers, risk stratification, and personalized thromboprophylaxis.

BACKGROUND:The risk of late recurrence after venous thromboembolism (VTE) related to weak transient risk factors (RFs) in young women guides thromboprophylaxis. OBJECTIVE:To estimate the incidence of recurring VTE in untreated women with a first episode due to combined oral contraceptives (COCs), pregnancy-puerperium, minor trauma-fracture, brief surgery, infection or brief immobility. METHODS:We performed a multicentre, international, observational, retrospective study on women aged 18-55 years old, free from high-risk thrombophilia and subsequently monitored. RESULTS:We studied 7,754 women over 43,880 patient.years (p.y.) and observed 1,318 VTE recurrences, corresponding to 3.00 (2.84-3.16) events for 100 p.y. Rates were higher if the initial clinical RF was pregnancy/puerperium, infection or brief surgery. Non-O blood group, the 3rd tertile of FIX activities and the 2nd and 3rd tertiles of FVIII activities were independent predictors of VTE recurrence. The overall risk of recurrence was 2.92 (2,66-3.18) per 100 p.y. in the subgroup of women with proximal deep vein thrombosis or pulmonary embolism. Class 1 obesity, the 3rd tertile of FIX activities and the 2nd and 3rd tertiles of FVIII activities were predictors. Combinations of predictors suggested that they might help define sub-groups that could benefit from chronic thromboprophylaxis. CONCLUSION:We confirm that young women with a first VTE related to weak transient RFs have an overall limited, but not anecdotal, risk of late recurrence, higher than 3% per year in subgroups. This risk is modulated by predictors, including categories of factors VIII and IX values, which could help to design the large-scale prospective studies still required.

The articles in this issue cover a wide range of topics, including the role of the maternal microbiome in fetal growth restriction, the effectiveness of therapy for mixed vaginitis, management strategies for pregnant women with COVID-19, the impact of environmental factors on reproductive health, thrombotic complications of chemotherapy, the connection between the microbiome and obesity, as well as rare clinical cases. Innovations in diagnostics, treatment, and screening are explored, from non-invasive prenatal testing to mathematical models for studying autism. The articles emphasize the importance of a comprehensive approach and the integration of modern technologies.

Combined oral contraceptives (COCs) remain one of the most popular reversible contraceptive methods worldwide. Still, regardless of the drug composition and duration of therapy, almost all COCs are associated with the risk of venous thrombosis. This review highlights the main pathogenetic mechanisms of thrombosis development during oral contraceptive use. Increase the production of certain clotting factors; a decrease in antithrombin and protein S levels; acquired resistance to activated protein C; a reduction in tissue factor pathway inhibitor (TFPI); indirect endothelial activation; inhibition of endogenous fibrinolysis; regulation of tissue factor by estradiol-sensitive microRNA; homocysteine imbalance caused by decreased intestinal reabsorption of folates and vitamin B-12; reduced bioavailability of nitric oxide (NO) due to high homocysteine levels; higher blood pressure, water retention, insulin resistance, increased levels of pro-inflammatory C-reactive protein (CRP) and uric acid, and antifibrinolytic (plasminogen activator inhibitor 1 type, PAI-1) biomarkers as consequences of NO deficiency; increased platelet adhesiveness and ADP-induced aggregation, which promote fibrinogen binding; and increased expression of pro-inflammatory cytokines are the main thrombotic effects of COCs use. Clinicians should carefully evaluate each patient's individual risk factors when prescribing COCs and conduct regular monitoring to reduce the risk of complications.

This narrative review summarizes the available literature on the association between In Vitro Fertilization (IVF) treatments and thrombosis, focusing on epidemiology and pathophysiology. Thrombosis is a rare IVF-related complication, with an incidence of approximately 0.2%, dramatically increased by ovarian hyperstimulation syndrome (OHSS). Arterial thrombosis, primarily associated with OHSS, is a rare and early event, while venous thrombosis, although more common, remains a rare complication of IVF. Venous thrombosis often affects the upper body. The thrombotic risk is higher during the first trimester of pregnancy obtained through IVF. This review discusses the impact of risk factors such as OHSS, thrombophilia, obesity, advanced maternal age, and polycystic ovarian syndrome, which predispose women to thromboembolic events during and after IVF stimulation.

Purpose: Cerebral vein thrombosis is a rare, life-threatening condition that has now become more commonly diagnosed due to advancements in imaging techniques. Our purpose is to improve understanding of pathogenesis, diagnosis and pregnancy and IVF management in patients with a history of cerebral thrombosis. Materials and methods: We present an overview of the modern tactics of anticoagulant therapy for cerebral thrombosis with a focus on pregnancy, the use of hormone therapy, and assisted reproductive technologies. Results: The most common risk factors for cerebral vein thrombosis are pregnancy, the postpartum period, and the use of oral contraceptives, which explains the high incidence of this pathology in women. The development of cerebral thrombosis is a vivid example of the interaction and synergetic effects of persistent factors that cause an increased risk of thrombotic complications, which include thrombophilia and acquired risk factors. Despite the possible risks, pregnancy after previously suffered cerebral thrombosis is not contraindicated provided adequate anticoagulant therapy. Conclusions: The most common provoking factors for the development of cerebral thrombosis in women are pregnancy and the use of estrogen-containing drugs. The issue of thromboprophylaxis during pregnancy, when using ART methods and the possibility of using hormonal therapy after cerebral vein thrombosis requires further study.

Background: Preeclampsia (PE) is a leading cause of maternal and perinatal morbidity worldwide, yet its mechanisms remain poorly understood. Dysregulated innate im-munity, specifically aberrant complement activation and excessive neutrophil extracel-lular traps (NETs) formation, contributes to endothelial dysfunction and inflammation in preeclampsia. However, the interaction between complement activation and NETs, as well as the differences between these immune pathways in early-onset and late-onset preeclampsia, remain unclear. To address this gap, we assessed complement components and NET markers across various preeclampsia phenotypes and examined their rela-tionships. Methods: Plasma samples were collected from 56 women with early-onset preeclampsia (EO-PE) before 34 weeks, 32 with late-onset preeclampsia (LO-PE) after 34 weeks, and 32 healthy pregnant women in the control group. Complement components (C1q, C3, C3a, C4, and the terminal complement complex, TCC) and NETs markers (MPO-DNA, cit-rullinated histone H3, and cathepsin G) were measured using ELISA. Group differences were assessed with non-parametric tests, and associations between markers and clinical variables were analyzed using Spearman correlations. Results: We observed higher levels of C1q, C3, C3a, and TCC in pregnant women with severe preeclampsia compared with healthy pregnancies (p < 0.001), while C4 levels remained unchanged. Among neutrophil trap biomarkers, MPO-DNA levels were el-evated in EO-PE (p = 0.019), while CitH3 and cathepsin G levels did not differ significantly between groups. Strong correlations were observed between MPO-DNA and TCC (ρ = 0.30, p = 0.013), as well as between cathepsin G and C3a (ρ = 0.40, p = 0.0007), indicating NETs–complement interactions. Patterns of complement and NETs activation were similar in early and late preeclampsia, despite differences in gestational age. Conclusions: The observed associations between MPO-DNA and TCC, and between cathepsin G and C3a, indicate meaningful crosstalk between NETs and complement ac-tivation. These findings support the role of innate immune dysregulation in preeclampsia and highlight NETs–complement interactions as potential targets for diagnostic and therapeutic approaches.

COVID-19 is one of the most dangerous diseases of the current decade that has significantly affected the overall morbidity, mortality, quality of health and life of global population. Among multiple early and late post-COVID complications observed in patients with a new coronavirus infection, perhaps the main place is held by thrombosis. The significant role of microthrombosis, disseminated intravascular coagulation, thrombotic angiopathies in COVID-19 pathogenesis is noted. The accumulated data from clinical studies and the presented expert opinions made it possible to establish the significance of the "immunothrombosis–NETosis–thromboinflammation" relationship in the pathological effects caused by SARS-CoV-2 virus, as well as to reveal the mechanisms underlying formation of thrombotic syndromes mediated by anticoagulant therapy and vaccination. The information obtained about hemostasis disorders allows to move deeper into understanding the long-term sequelae in COVID-19 convalescent patients.

Background-Obstetric hemorrhage is a life-threatening complication of pregnancy. Systematic collection of data on transfusion practice during pregnancy and post-partum period are scarce, as well as data on fetal or neonatal outcomes of women transfused during pregnancy. We examined the prevalence of obstetric hemorrhage and outcome of pregnancies in hospitalized transfused women. Materials and methods-This is a retrospective cohort study collecting clinical and laboratory data of women transfused from 2015 to 2017 in three Italian Tertiary level Obstetrical Departments. Inclusion criteria were: 1) age >18 years; 2) antepartum or peripartum hospital admission and 3) transfusion during the hospital stay of at least one unit of packed red blood cell (RBC) units. Women below 18 years and/or with transfusion outside pregnancy were excluded. During the observation period, 18,495 women gave birth across the three Obstetrics Departments: transfusion rate was 1.7%. Results-315 women were included in the final analysis. Most (75.2%) needed transfusion from 35 weeks onwards. A percentage higher that that observed in general population of transfused women showed co-morbidities such as hypertensive disorders or diabetes (13.9 vs 5.5%). We recorded 90% of live births and 7.6% of Intra Uterine Fetal Demise or neonatal death. Perinatal outcomes were impacted by the dose of transfusion: logistic regression, correcting for age and assisted conception, showed that women transfused with 3 or more RBC units have about 3-fold higher risk of perinatal death (OR: 2.9, 95% CI: 1.0-8.4). Discussion-In this series, several known risk factors were associated with adverse feto-neonatal outcome. In addition, the number of RBC units transfused was significantly and independently associated with the perinatal outcome. Present data can be helpful to design prospective studies taking into account timing and dose of transfusion during pregnancy with the objective to improve feto-maternal outcome.

This article explores systemic inflammatory response syndrome (SIRS), thromboinflammation, and septic shock in fetuses and neonates, offering a comprehensive examination of their pathophysiology, diagnostic criteria, and clinical implications. It identifies SIRS as an exaggerated response to external stress, disrupting the balance between inflammation and adaptive mechanisms, driven by cytokines such as TNF-α and IL-1. The fetal inflammatory response syndrome (FIRS), a subset of SIRS, is noted for its role in adverse neonatal outcomes, including organ damage, inflammation, and long-term developmental disorders. The article discusses the extensive effects of FIRS on critical systems, including the blood, lungs, central nervous system, and kidneys. It highlights the challenges in diagnosing and managing septic shock in neonates, focusing on the relationship between inflammation and the hemostatic system. Additionally, the paper points out recent advancements, such as the convergent model of coagulation and emerging biomarkers like microRNAs for early detection. Despite this progress, gaps remain in understanding the molecular mechanisms underlying these conditions and in developing effective therapeutic strategies. This highlights the necessity for targeted research to mitigate the morbidity and mortality associated with septic shock in neonates.

Cancer patients are at risk of developing arterial and venous thrombosis during chemotherapy (CT) and after its cessation. A prothrombotic risk may arise via pathogenetic pathways such as activation of external and internal coagulation pathways, decreased anticoagulant levels, platelet activation, fibrinolysis blockade, etc. Chemotherapeutic agents exert direct cytotoxicity, as well as indirectly suppress cellular processes necessary for tumor cell proliferation. CT-related cytotoxicity act on both tumor and healthy body cells. Available targeted drugs with improved selectivity for tumor cells are also associated with thrombosis risk. Low molecular weight heparins, which effectively reduce the risk of venous thromboembolism, have not yet been officially recommended for routine use during CT. Here, we discuss the prothrombotic effects of various antitumor agents aimed at gaining deeper understanding of the underlying mechanisms that may allow to develop new strategies for prevention and treatment of such formidable complications.

Congenital connective tissue diseases are numerous disorders that are associated with connective tissue pathology, involving different organs and systems: musculoskeletal, cardiovascular, ocular, etc. Objective. To study the features of pregnancy course in patients with mesenchymal connective tissue dysplasias. Patients and methods. The course of pregnancy and labor in 56 women aged 18 to 36 years with congenital connective tissue dysplasias (CTDs) was analyzed: 23 patients with Marfan syndrome, 22 with Ehlers–Danlos syndrome, and 11 with hereditary hemorrhagic telangiectasia. Results. All patients with congenital CTD had hemorrhagic manifestations during pregnancy. They also had a significantly increased incidence of both obstetric and hemorrhagic complications during pregnancy, labor, and postpartum period. The high incidence of fetal growth restriction in pregnant women with congenital CTD may be due to abnormalities in the structure of connective tissue of the uteroplacental vascular complex. In general, patients with congenital CTD are at higher risk of perinatal morbidity. Conclusion. The decision on the possibility of pregnancy for each woman with congenital CTD is made individually. Given the high risk of life-threatening complications during vaginal delivery, cesarean section is recommended for most of these patients. Key words: congenital connective tissue diseases, mesenchymal dysplasias, Marfan syndrome, Ehlers–Danlos syndrome, Osler–Weber–Rendu syndrome, hereditary hemorrhagic telangiectasia, gestational process, pregnancy, aortic dissection in pregnancy, hemorrhage

Thrombotic microangiopathy (TMA) encompasses a range of disorders characterized by blood clotting in small blood vessels, leading to organ damage. It can manifest as various syndromes, including thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS), and others, each with distinct causes and pathophysiology. Thrombo-inflammation plays a significant role in TMA pathogenesis: inflammatory mediators induce endothelial injury and activation of platelet and coagulation cascade, contributing to microvascular thrombosis. Primary TMA, such as TTP, is primarily caused by deficient ADAMTS13 metalloproteinase activity, either due to antibody-mediated inhibition or intrinsic enzyme synthesis defects. In cancer patients, a significant reduction in ADAMTS13 levels and a corresponding increase in VWF levels is observed. Chemotherapy further decreased ADAMTS13 levels and increased VWF levels, leading to an elevated VWF/ADAMTS13 ratio and increased thrombotic risk. Drug-induced TMA (DITMA) can result from immune-mediated or non-immune-mediated mechanisms. Severe cases of COVID-19 may lead to a convergence of syndromes, including disseminated intravascular coagulation (DIC), systemic inflammatory response syndrome (SIRS), and TMA. Treatment of TMA involves identifying the underlying cause, implementing therapies to inhibit complement activation, and providing supportive care to manage complications. Plasmapheresis may be beneficial in conditions like TTP. Prompt diagnosis and treatment are crucial to prevent serious complications and improve outcomes.

Caesarean section is one of the ancient and most outstanding operations, with roots going deep into the past. It shows unmatched significance in that it is the only operation responsible for the lives of two people – mother and child. Hypotheses about the origin of the term a Сaesarean section, the history of its development and methods underlying execution the operation are discussed here. The article highlights issues aimed at Сaesarean section in fine art, the historical stages of this operation and their reflection in fine arts. Studying artistic works related to Caesarean section helps us to better understand its impact on mankind and social consciousness.

The article analyzes a clinical case of the development of thrombotic microangiopathy in a patient with ovarian cancer during chemotherapy, which manifested in the form of renal failure. An analysis of laboratory and biochemical findings is given, which were initially incorrectly interpreted and only a kidney biopsy made it possible to make a correct diagnosis and begin pathogenetic treatment. Cancer patients are at increased risk for developing secondary TMA, which requires increased attention to symptoms uncharacteristic of the underlying disease.

SARS-CoV-2 has specific direct and indirect effects on the vascular endothelium, immune system, and hemostasis, thereby promoting endothelial dysfunction, immunothrombosis, and the formation of neutrophil extracellular traps (NETs). In recent years, there has been increasing evidence that endothelial dysfunction, immunothrombosis, and NETosis contribute to the clinical manifestations associated with COVID-19. Endothelial dysfunction is a common denominator of many clinical aspects of severe COVID-19. A better understanding of the pathophysiology of complications may significantly impact patient management and provide more effective personalized therapy. The aim of this review was to summarize the pathophysiology of endothelial dysfunction and immunothrombosis in COVID-19. Key words: COVID-19, thromboinflammation, immunothrombosis, neutrophil extracellular traps, NETosis, endotheliopathy

The article highlights issues aimed at maternal death in literature. The literary works of Tolstoy, Turgenev, Bunin, Rabelais, Martin, Pushkin, Mann, etc., are discussed.