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1.
Obstetrics, Gynecology and Reproduction ; 16(3):228-243, 2022.
Article in Russian | EMBASE | ID: covidwho-1979784

ABSTRACT

Introduction. Currently, endothelial dysfunction caused by inflammation and immunothrombosisis considered as one of the crucial mechanisms in developing the SARS-CoV-2 virus-mediated coronavirus disease 2019 (COVID-19). A mass endothelial damage followed by release of untypical large quantity of von Willebrand factor (vWF) multimers and subsequent consumption of metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) is described during severe COVID-19. The activation of innate immune cells including neutrophils results in formation of neutrophil extracellular traps (NETs) and myeloperoxidase (MPO) release that, in turn, contributes to spread of inflammation and microvascular thrombosis. Aim: to evaluate a pathogenetic role and predictive significance for serum markers of inflammation, endothelial dysfunction and hemostatis activation such as vWF, ADAMTS-13 and MPO for in-hospital mortality in severe COVID-19 patients requiring mechanical lung ventilation. Materials and Methods. There was performed a single-center observational study with 129 severe COVID-19 patients on mechanical lung ventilation at the intensive care unit, by assessing serum in all subjects vWF, ADAMTS-13 as well as in 79 patients MPO level along with other potential predictors for in-hospital mortality. Results. A multivariate analysis revealed that increased serum level for vWF antigen (vWF:Ag) and MPO antigen (MPO:Ag) were significantly and independently related to high mortality probability: vWF:Ag (IU/ml) - adjusted odds ratio (OR) = 3.360;95 % confidence interval (95 % Cl) = 1.562-7,228 (р = 0,0019);MPO:Ag (ng/ml) - adjusted OR = 1.062;95 % = 1.024-1.101 (p = 0.0011). Such data allowed to obtained a simplified mortality score for categorizing patients as those having a higher or lower score compared with the median score level: a high score was associated with lower cumulative survival rate (p < 0.0001), with 50 % of the cases linked to lethal outcome on day 13 post-hospital admission. Conclusion. Severe COVID-19 patients requiring mechanical lung ventilation were found to have elevated level of serum MPO activity and vWF correlating with poor survival.

2.
Obstetrics, Gynecology and Reproduction ; 16(2):204-212, 2022.
Article in Russian | EMBASE | ID: covidwho-1957619

ABSTRACT

The main role of platelets is traditionally assigned to participation in hemostasis reactions. In recent years, the data have appeared on the non-hemostatic platelet-related role and their active participation in inflammatory reactions. These platelet functions are predetermined by their ability to activate and secrete various immunomodulatory cytokines and chemokines. In addition, activated platelets can directly interact with viral receptors. Recently, there has been growing the knowledge regarding platelet-related regulation of diverse cell types. The result of this interaction is, among others, the formation of platelet-leukocyte aggregates, the focusing of neutrophils at the sites of injury, and generation of a scaffold for developing extracellular traps. Thus, platelets are not only participants in coagulation processes, but also important players in the inflammatory process. This lecture details the issues of platelets controlling and modulating host response to viral infection, as well as potential targets for therapeutic intervention.

3.
Obstetrics, Gynecology and Reproduction ; 16(2):158-175, 2022.
Article in Russian | EMBASE | ID: covidwho-1957618

ABSTRACT

These days, anticoagulants are in great demand. They are used as a prophylaxis for thromboembolic complications in various diseases and conditions in general therapeutic practice, cardiology, neurology, as well as obstetrics to manage high-risk pregnancies. The relevance of anticoagulants competent use has come to the fore in connection with the emergence of a new disease – COVID-19 and its serious complications such as developing thrombotic storm, in which the timely applied anticoagulant therapy is the key to the success of therapy. The risk of bleeding should be considered when using any anticoagulant. Age, impaired renal function and concomitant use of antiplatelet agents are common risk factors for bleeding. Moreover, only vitamin K antagonists and heparin have specific antidotes – vitamin K and protamine, respectively. Inhibitors of other anticoagulants are universal presented as inactivated or activated prothrombin complex concentrate and recombinant factor VIIa. Hemodialysis effectively reduces dabigatran concentration, activated charcoal is effective in the case of recent oral administration of lipophilic drugs. Research on new antidotes of currently available anticoagulants is under way, similar to testing of new types of anticoagulants that are sufficiently effective in preventing and treating thromboembolic complications with minimal risk of hemorrhagic. The main contraindication to anticoagulants use is the doctor's ignorance of the mechanisms of drug action and opportunities for suppressing its effect.

4.
J Matern Fetal Neonatal Med ; 35(16): 3044-3048, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1908605

ABSTRACT

There is a global problem of increment of the number of children with clinical features that mimic Kawasaki Disease (KD) during the ongoing Coronavirus Disease 2019 (COVID-19) pandemic. The disease was first reported by Tomisaku Kawasaki, a Japanese pediatrician, in a four-year-old child with a rash and fever at the Red Cross Hospital in Tokyo in January 1961. Now Kawasaki disease is recognized worldwide. The complexity of symptoms was defined as an «acute febrile mucocutaneous lymphnode syndrome". At the moment, it is still unclear whether the coronavirus itself can lead to development of mucocutaneous lymph node syndrome. However, it is believed that COVID-19 virus infection worsens the course of Kawasaki disease, and in some cases, children affected by SARS-V-2 may develop a disease that has a clinical picture similar to Kawasaki disease.


Subject(s)
COVID-19 , Mucocutaneous Lymph Node Syndrome , COVID-19/complications , Child , Child, Preschool , Fever , Humans , Mucocutaneous Lymph Node Syndrome/complications , Mucocutaneous Lymph Node Syndrome/diagnosis , Mucocutaneous Lymph Node Syndrome/epidemiology , Pandemics , SARS-CoV-2
5.
Obstetrics, Gynecology and Reproduction ; 15(6):639-657, 2021.
Article in Russian | Scopus | ID: covidwho-1698694

ABSTRACT

As shown by numerous studies conducted during the pandemic, the severe course of COVID-19 is accompanied by multiple organ failure. Cytokine storm, hypercoagulation, complement hyperactivation and other arms comprise the overall picture of the pathogenesis of the severe disease course. The frequent diagnosis of multiple microvascular thrombosis in lung, heart, and kidneys, as well as the presence of platelet-fibrin thrombi there and signs of terminal organ damage, suggest a possible involvement of thrombotic microangiopathy (TMA) in the development of multiple organ failure. In this regard, it is especially important to timely diagnose TMA and start pathogenetic therapy. These measures can significantly reduce mortality due to the novel disease. Heparins and direct oral anticoagulants are the mainstay for prevention and treatment of venous thromboembolism in patients with COVID-19, but their effectiveness in the presence of TMA is questionable. It has been proven that anticoagulants use in critically ill patients with COVID-19 for prevention of large vessel thrombosis is effective, but their role in the prevention of microthrombosis is not clear. Here we review the currently available information on thrombotic microangiopathy, as well as a review of literature data describing TMA-like conditions in COVID-19, discuss potential pathophysiology of the condition development and proposed therapeutic approaches. © Obstetrics, Gynecology and Reproduction 2021.

6.
Obstetrics, Gynecology and Reproduction ; 15(5):562-572, 2021.
Article in English | Scopus | ID: covidwho-1551950

ABSTRACT

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 AstraZeneca (ChAdOx1) and J&J/Janssen adenovirus vector vaccines. The syndrome called VITT (vaccine-induced immune thrombotic thrombocytopenia) is manifested as thrombosis simultaneously with decreased platelet count, significantly increased D-dimer levels and detected anti-factor 4 platelet (PF4) antibodies. We present a detailed review on the epidemiology, pathogenesis, clinical picture, diagnostics and treatment of VITT, which by its nature is 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 able to reduce the incidence of severe cases, stop the spread of COVID-19 infection and 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 abnormal immune response to some variants of vaccines against COVID-19, cannot be translated to other vaccines (including those registered in the Russian Federation) and, moreover, cannot be a reason to refuse their administration. © 2021 Obstetrics, Gynecology and Reproduction. All rights reserved.

7.
Obstetrics, Gynecology and Reproduction ; 15(5):499-514, 2021.
Article in English | Scopus | ID: covidwho-1551949

ABSTRACT

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 increased 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. © 2021 Obstetrics, Gynecology and Reproduction. All rights reserved.

8.
Obstetrics, Gynecology and Reproduction ; 15(3):313-320, 2021.
Article in English | EMBASE | ID: covidwho-1527054

ABSTRACT

The novel coronavirus epidemic is characterized by high rates of morbidity and relatively high mortality. Laboratory test results in patients include leukopenia, an increase in liver function tests and ferritin levels reaching hundreds, and sometimes thousands of units. These data remind us about the macrophage activation syndrome (MAC). Secondary hemophagocytic lymphohistiocytosis syndrome, MAC, which pathogenesis is based on a defect in the mechanisms of T-cell cytotoxicity and decreased level of natural killer cells associated with the defect in the perforin-encoding gene as well as hyperproduction of a number of cytokines - interleukin (IL)-1β, tumor necrosis factor-α, etc. by T-lymphocytes and histiocytes, indirectly leading to the activation of macrophages and production of proinflammatory cytokines, in particular IL-6 hyperproduction. MAC is one of "hyperferritinemic syndromes". These disorders have similar clinical and laboratory manifestations, and they also respond to similar treatments, suggesting that hyperferritinemia may be involved in the overall pathogenesis and is characterized by elevated ferritin level and cytokine storm. Despite the fact that data on the immune and inflammatory status in patients with COVID-19 have only started to appear, it is already clear that hyperinflammation and coagulopathy affect the disease severity and increase the risk of death in patients infected with SARS-CoV-2. Hence, understanding the pathogenesis of the novel coronavirus infection can help in its early diagnostics and treatment.

9.
Obstetrics, Gynecology and Reproduction ; 15(4):335-350, 2021.
Article in English | EMBASE | ID: covidwho-1449369

ABSTRACT

Numerous studies have proven a close relationship between inflammatory diseases and the state of hypercoagulability. In fact, thromboembolic complications represent one of the main causes of disability and mortality in acute and chronic inflammatory diseases, cancer and obstetric complications. Despite this, the processes of hemostasis and immune responses have long been considered separately;currently, work is underway to identify the molecular basis for a relationship between such systems. It has been identified that various pro-inflammatory stimuli are capable of triggering a coagulation cascade, which in turn modulates inflammatory responses. Neutrophil extracellular traps (NETs) are the networks of histones of extracellular DNA generated by neutrophils in response to inflammatory stimuli. The hemostasis is activated against infection in order to minimize the spread of infection and, if possible, inactivate the infectious agent. Another molecular network is based on fibrin. Over the last 10 years, there has been accumulated a whole body of evidence that NETs and fibrin are able to form a united network within a thrombus, stabilizing each other. Similarities and molecular cross-reactions are also present in the processes of fibrinolysis and lysis of NETs. Both NETs and von Willebrand factor (vWF) are involved in thrombosis as well as inflammation. During the development of these conditions, a series of events occurs in the microvascular network, including endothelial activation, NETs formation, vWF secretion, adhesion, aggregation, and activation of blood cells. The activity of vWF multimers is regulated by the specific metalloproteinase ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13). Studies have shown that interactions between NETs and vWF can lead to arterial and venous thrombosis and inflammation. In addition, the contents released from activated neutrophils or NETs result in decreased ADAMTS-13 activity, which can occur in both thrombotic microangiopathies and acute ischemic stroke. Recently, NETs have been envisioned as a cause of endothelial damage and immunothrombosis in COVID-19. In addition, vWF and ADAMTS-13 levels predict COVID-19 mortality. In this review, we summarize the biological characteristics and interactions of NETs, vWF, and ADAMTS-13, the effect of NETs on hemostasis regulation and discuss their role in thrombotic conditions, sepsis, COVID-19, and obstetric complications.

10.
Vestnik Rossiiskoi Akademii Meditsinskikh Nauk ; 75(1):83-92, 2020.
Article in Russian | EMBASE | ID: covidwho-1244381

ABSTRACT

The rapid spread of COVID-19 and the large number of cases put a significant burden on the health systems of any developed country. Specialists in natural disasters and military medicine should be involved in the provision of medical care and observance of anti-epidemic measures. In some countries, including Italy, they were involved only after the situation was dramatically worsening with many clinical units and hospitals overloaded by infected patients. To curb the spread of COVID-19, most countries declared a state of emergency, and unprecedented measures have been taken to strengthen quarantine in suspected or positive symptomatic subjects. Nevertheless, the crisis associated with the unexpectedly global scale and tragedy of the pandemic and the inconsistency of actions of both society and individuals and specialized medical services, lead to insufficient effectiveness of the measures taken in a number of regions. In the present day, it is vital for every person to change its mindset ― relying on personal responsibility to comply with all recommendations of quarantine and anti-epidemic measures, and to reorganize departments and resources of medical institutions at all levels in order to withstand the spread of infection and at the same time provide all those in need with the necessary and appropriate medical care. Particular attention should be paid to the obstetric care service, given that even in “normal” times, the obstetric hospital is an area of increased responsibility for the life and health of mother and child and future mankind. Fulfillment of existing orders, instructions of national and regional committees, international and national protocols and clinical protocols should undoubtedly lead to a positive result, but this requires additional training of medical personnel at all levels. The purpose of this review is to propose quick key strategies for reassessing the maternity and neonatal wards/ hospitals based on the experience of health systems and organizations which faced the spread of this new coronavirus;this advice may be applied along with binding tight instructions in obstetric hospitals in order to proactively respond to a likely wave of growth in COVID-19.

11.
Obstetrics, Gynecology and Reproduction ; 14(3):374-383, 2020.
Article in Russian | EMBASE | ID: covidwho-903106

ABSTRACT

An issue of habitual miscarriage poses a high social importance especially during COVID-19 pandemic. Meanwhile, healthcare workers faced a mass media campaign against using micronized progesterone upon habitual miscarriage, which, as viewed by us, displays signs of prejudiced data manipulation and may disorient practitioners. In this Letter we provide objective information on accumulated data regarding gestagenes efficacy and safety. We invoke healthcare professionals to make decisions deserving independent primary source trust presented by original scientific papers published in peer-reviewed journals, clinical recommendations proposed by professional medical communities as well as treatment standards and protocols.

12.
Obstetrics, Gynecology and Reproduction ; 14(3):314-326, 2020.
Article in Russian | EMBASE | ID: covidwho-903105

ABSTRACT

Recently, it has been increasingly apparent that sepsis and septic shock become a pressing issue. Over the last decade, incidence rate of sepsis in obstetrics and gynecology has been increased by more than 2-fold. Here we review clinical forms of septic conditions, risk factors, pathogenesis of sepsis and septic shock, as well as major pathogens resulting in septic conditions. Special attention is paid to neonatal sepsis. The relationship between septic shock and viral infections is considered in the context of the novel coronavirus infection (COVID-19) pandemic caused by SARS-CoV-2. Impaired hemostasis is discussed in patients with septic shock, including those with disseminated intravascular coagulation (DIC). An importance of assessing ADAMTS-13 level to refine disease prognosis is discussed.

13.
Obstetrics, Gynecology and Reproduction ; 14(2):132-147, 2020.
Article in English | EMBASE | ID: covidwho-842276

ABSTRACT

The pandemic of a novel coronavirus infection COVID-19 has become a real challenge to the mankind and medical community and has raised a number of medical and social issues. Based on the currently available information on COVID-19 clinical cases, it follows that COVID-19 patients in critical condition exhibit a clinical picture of disseminated intravascular coagulation (DIC), septic shock with developing multiple organ failure, which justifies use of anticoagulant therapy in COVID-19 patients. In addition to isolating virus RNA from biological material and polymerase chain reaction diagnostics, use of simple and easily accessible laboratory blood markers is necessary for management of COVID-19 patients. If the activation of coagulation processes is sufficient enough, consumption of platelets and blood clotting factors can be diagnosed by laboratory methods as prolongation of routine blood clotting tests and increasing thrombocytopenia. Hyperfibrinogenemia, increased D-dimer level, prolonged prothrombin time, thrombocytopenia, lymphopenia, leukocytopenia, increased concentration of interleukin-6 and ferritin are observed in most COVID-19 patients. The degree of increase in these changes correlates with severity of the inflammatory process and serves as a prognostically unfavorable sign. Here we discuss value of laboratory monitoring playing an essential role in such pathological crisis that contributes to patient screening, diagnosis as well as further monitoring, treatment and rehabilitation.

14.
Obstetrics, Gynecology and Reproduction ; 14(2):229-238, 2020.
Article in Russian | Scopus | ID: covidwho-831744

ABSTRACT

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the genus Flavivirus and the Flaviviridae family. In 1947 and 1948 ZIKV was first isolated from a nonhuman primate as well as from mosquitoes in Africa, respectively. For half a century, ZIKV infections in human were sporadic prior to 2015-2016 pandemic spreading. Transmission of ZIKV from mother to fetus can occur in any trimester of pregnancy, even if mother was an asymptomatic carrier. The clinical signs of ZIKV infection are nonspecific and can be misdiagnosed as some other infectious diseases, especially those caused by arboviruses such as Dengue and Chikungunya. ZIKV infection was solely associated with mild illness prior to the large French Polynesian and Brazil outbreaks, when severe neurological complications, Guillain-Barre syndrome and dramatically increased rate of severe congenital malformations (including microcephaly) were reported. The adaptation of ZIKV to an urban cycle in endemic areas suggests that the incidence of ZIKV infections may be underestimated. The pandemic of novel coronavirus infection (COVID-19) demonstrates that lessons from ZIKV pandemic propagation has not been learned properly. © 2020 Universidad de Antioquia. All rights reserved.

15.
J Matern Fetal Neonatal Med ; 35(13): 2536-2544, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-632431

ABSTRACT

For last months, humanity has faced a formidable unknown enemy, which is presented as a new coronavirus infection. Despite the fact that the causative agents of new diseases appear at a certain frequency and that the virus SARS-CoV-2 has certain common properties with its predecessors, at the moment we are dealing with a new unknown pathogenesis of the development of severe complications in patients with risk factors. A final understanding of pathological process mechanisms is the goal of the scientific community. Summarizing research data from different countries, it became obvious that in severe cases of viral infection, we are dealing with a combination of the systemic inflammatory response syndrome, disseminated intravascular coagulation and thrombotic microangiopathy (TMA). Thrombotic microangiopathy is represented by a group of different conditions in which thrombocytopenia, hemolytic anemia, and multiple organ failure occur. The article reflects the main types of TMA, pathogenesis and principles of therapy. The main participants in the process are described in detail, including the von Willebrand factor and ADAMTS-13. Based on the knowledge available, as well as new data obtained from patients with COVID-19, we proposed possible models for the implementation of conditions such as sepsis, TMA, and DIC in patients with severe new coronavirus infection. Through a deeper understanding of pathogenesis, it will be possible to develop more effective diagnosis and therapy.


Subject(s)
COVID-19 , Disseminated Intravascular Coagulation , Thrombotic Microangiopathies , COVID-19/complications , Dacarbazine , Disseminated Intravascular Coagulation/diagnosis , Female , Humans , Pregnancy , SARS-CoV-2 , Thrombotic Microangiopathies/diagnosis , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/therapy
16.
Annals of the Russian academy of medical sciences / Вестник Российской академии медицинских наук ; 75(1):83-92, 2020.
Article | WHO COVID | ID: covidwho-71763

ABSTRACT

The rapid spread of COVID-19 and the large number of cases put a significant burden on the health systems of any developed country. Specialists in natural disasters and military medicine should be involved in the provision of medical care and observance of anti-epidemic measures. In some countries, including Italy, they were involved only after the situation was dramatically worsening with many clinical units and hospitals overloaded by infected patients. To curb the spread of COVID-19, most countries declared a state of emergency, and unprecedented measures have been taken to strengthen quarantine in suspected or positive symptomatic subjects. Nevertheless, the crisis associated with the unexpectedly global scale and tragedy of the pandemic and the inconsistency of actions of both society and individuals and specialized medical services, lead to insufficient effectiveness of the measures taken in a number of regions. In the present day, it is vital for every person to change its mindset ― relying on personal responsibility to comply with all recommendations of quarantine and anti-epidemic measures, and to reorganize departments and resources of medical institutions at all levels in order to withstand the spread of infection and at the same time provide all those in need with the necessary and appropriate medical care. Particular attention should be paid to the obstetric care service, given that even in normal times, the obstetric hospital is an area of increased responsibility for the life and health of mother and child and future mankind. Fulfillment of existing orders, instructions of national and regional committees, international and national protocols and clinical protocols should undoubtedly lead to a positive result, but this requires additional training of medical personnel at all levels. The purpose of this review is to propose quick key strategies for reassessing the maternity and neonatal wards/ hospitals based on the experience of health systems and organizations which faced the spread of this new coronavirus;this advice may be applied along with binding tight instructions in obstetric hospitals in order to proactively respond to a likely wave of growth in COVID-19. ;Актуальность. Быстрое распространение COVID-19 и большое количество заболевших накладывает значительную нагрузку на системы здравоохранения развитых государств. Ð’ ряде стран к оказанию медицинской помощи и соблюдению противоэпидемических мероприятий привлекаются специалисты по стихийным бедствиям и военной медицине, однако в некоторых странах, в том числе в Италии, они были задействованы после того, как многие клинические подразделения и стационары были перегружены. Для сдерживания распространения COVID-19 большинство стран объявили чрезвычайное положение, были приняты беспрецедентные меры по усилению карантинных мероприятий. Тем не менее кризис, связанный с неожиданно глобальным масштабом и трагичностью пандемии, и несогласованность действий как общества и отдельных граждан, так и специализированных медицинских служб приводят к недостаточной эффективности проводимых мероприятий в ряде регионов. Особое внимание следует уделить службе родовспоможения, учитывая, что и в спокойное время акушерский с ‚ационар является зоной повышенной ответственности за жизнь и здоровье матери и ребенка. Исполнение действующих приказов, указаний национальных и региональных комитетов, международных/национальных и клинических протоколов, несомненно, приведет к положительному результату, но требует дополнительного обучения и тренировки медицинского персонала всех уровней. Цель обзора ― предложить ключевые стратегии, основываясь на опыте регионов, ранее столкнувшихся с распространением нового коронавируса, которые могут быть быстро применены наряду с обязательными к исполнению действующими приказами и распоряжениями в акушерских стационарах, чтобы превентивно отреагировать на вероятную волну роста заболеваемости и носительства COVID-19.

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