Clinical significance of assessing ADAMTS-13 and von Willebrand factor level in COVID-19 convalescent pregnant women.

Introduction. Coronavirus infection is associated with severe endotheliopathy, thromboinflammation and immunothrombosis leading to excessive release of von Willebrand factor (vWF) multimers from Weibel-Palade bodies, which can affect activity of ADAMTS-13 metalloproteinase (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and the ADAMTS-13/vWF axis previously shown by us to be altered in non-pregnant women with severe COVID-19. Aim(s): to study a clinical role of hemostasis activation particularly ADAMTS-13/vWF axis in pregnant women after COVID-19. Materials and Methods. A prospective case-control study was conducted with pregnant women (n = 135) divided into 3 groups: group 1 included 45 women with prior COVID-19 during pregnancy, group 2 - 45 women in the acute phase of the infection during pregnancy, group 3 - 45 healthy pregnant women. The level of vWF and ADAMTS-13 was assessed in all patients. Results. The concentration of vWF antigen (vWF:Ag) in the acute period of the disease in pregnant women with COVID-19 was significantly higher compared to the control group (p < 0.001). ADAMTS-13 level in pregnant women after COVID-19 did not differ from that of in control group, while vWF level was significantly higher in 66.7 % (30/45). The ADAMTS-13/vWF ratio was increased and significantly differed both in pregnant patients during the acute period of the disease (p < 0.001) and pregnant women after infection (p = 0.0002) compared with the control group. Conclusion. Our results show that endotheliopathy was prominently manifested in pregnant women with COVID-19 and persisted for several months after disease. The ADAMTS-13/vWF ratio determines the pathway functioning, the risk of microcirculation disorders and clinical complications.Copyright © 2023 Vestnik Sankt-Peterburgskogo Universiteta, Yazyk i Literatura. All rights reserved.

Functioning of the ADAMTS-13/vWF axis and its clinical significance

Advances in biology have allowed us to substantially deepen our knowledge about hemostasis functioning both in health and disease. ADAMTS-13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and von Willebrand factor (vWF) are components of the hemostasis system, which physiological interaction holds an important place in maintaining homeostasis. ADAMTS-13 is a metalloproteinase mainly acting to release vWF fragments into the blood plasma, as well as regulating its activity by cleaving ultra-large vWF multimers (UL-vWF) into smaller and less active forms. The study of such factors is of great clinical importance, since a decrease in ADAMTS-13 activity and an increase in vWF level can be predictors of microcirculatory disorders that play an important role in developing multiple organ failure. However, very few and fully contradictory studies devoted to the physiological aspects of the ADAMTS-13/vWF axis functioning in the mother-fetus system are available, therefore requiring to be further investigated.Copyright © 2023 Russian Journal of Forensic Medicine. All rights reserved.

Clinical significance of assessing ADAMTS-13 and von Willebrand factor level in COVID-19 convalescent pregnant women

Introduction. Coronavirus infection is associated with severe endotheliopathy, thromboinflammation and immunothrombosis leading to excessive release of von Willebrand factor (vWF) multimers from Weibel-Palade bodies, which can affect activity of ADAMTS-13 metalloproteinase (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and the ADAMTS-13/vWF axis previously shown by us to be altered in non-pregnant women with severe COVID-19. Aim: to study a clinical role of hemostasis activation particularly ADAMTS-13/vWF axis in pregnant women after COVID-19. Materials and Мethods. A prospective case-control study was conducted with pregnant women (n = 135) divided into 3 groups: group 1 included 45 women with prior COVID-19 during pregnancy, group 2 - 45 women in the acute phase of the infection during pregnancy, group 3 - 45 healthy pregnant women. The level of vWF and ADAMTS-13 was assessed in all patients. Results. The concentration of vWF antigen (vWF:Ag) in the acute period of the disease in pregnant women with COVID-19 was significantly higher compared to the control group (p < 0.001). ADAMTS-13 level in pregnant women after COVID-19 did not differ from that of in control group, while vWF level was significantly higher in 66.7 % (30/45). The ADAMTS-13/vWF ratio was increased and significantly differed both in pregnant patients during the acute period of the disease (p < 0.001) and pregnant women after infection (p = 0.0002) compared with the control group. Conclusion. Our results show that endotheliopathy was prominently manifested in pregnant women with COVID-19 and persisted for several months after disease. The ADAMTS-13/vWF ratio determines the pathway functioning, the risk of microcirculation disorders and clinical complications. © 2023 Vestnik Sankt-Peterburgskogo Universiteta, Yazyk i Literatura. All rights reserved.

Clinical significance of assessing ADAMTS-13 and von Willebrand factor level in COVID-19 convalescent pregnant women.

Introduction. Coronavirus infection is associated with severe endotheliopathy, thromboinflammation and immunothrombosis leading to excessive release of von Willebrand factor (vWF) multimers from Weibel-Palade bodies, which can affect activity of ADAMTS-13 metalloproteinase (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) and the ADAMTS-13/vWF axis previously shown by us to be altered in non-pregnant women with severe COVID-19. Aim(s): to study a clinical role of hemostasis activation particularly ADAMTS-13/vWF axis in pregnant women after COVID-19. Materials and Methods. A prospective case-control study was conducted with pregnant women (n = 135) divided into 3 groups: group 1 included 45 women with prior COVID-19 during pregnancy, group 2 - 45 women in the acute phase of the infection during pregnancy, group 3 - 45 healthy pregnant women. The level of vWF and ADAMTS-13 was assessed in all patients. Results. The concentration of vWF antigen (vWF:Ag) in the acute period of the disease in pregnant women with COVID-19 was significantly higher compared to the control group (p < 0.001). ADAMTS-13 level in pregnant women after COVID-19 did not differ from that of in control group, while vWF level was significantly higher in 66.7 % (30/45). The ADAMTS-13/vWF ratio was increased and significantly differed both in pregnant patients during the acute period of the disease (p < 0.001) and pregnant women after infection (p = 0.0002) compared with the control group. Conclusion. Our results show that endotheliopathy was prominently manifested in pregnant women with COVID-19 and persisted for several months after disease. The ADAMTS-13/vWF ratio determines the pathway functioning, the risk of microcirculation disorders and clinical complications.Copyright © 2023 Vestnik Sankt-Peterburgskogo Universiteta, Yazyk i Literatura. All rights reserved.

Prognostic value of von Willebrand factor in clinical practice

The von Willebrand factor (vWF) is a multimeric plasma glycoprotein, which quantification has important prognostic value. The current literature review demonstrates a relationship between the disease severity and vWF level. For example, von Willebrand disease is characterized by a quantitative/qualitative genetic vWF deficiency resulting in potentially developed massive bleeding, which knowledge can prevent development of formidable complications. We should also not forget about an opportunity of developing acquired Willebrand syndrome most often occurring in response to autoimmune diseases. A marked vWF increase during pregnancy may evidence about developing preeclampsia, whereas in newborns exposed to additional risk factors, it can lead to thrombosis. In cancer patients, a substantially elevated vWF level correlates with low survival, especially in those with ovarian cancer, glioblastomas, esophageal and lung cancer. The emergence of a novel coronavirus infection COVID-19 allowed us to take a fresh look at prognostic value of vWF, because numerous studies show that increased blood plasma vWF:Ag is associated with more adverse outcome in patients with COVID-19. Here, we demonstrate an importance of determining vWF level, because early diagnostics and treatment can improve the outcomes of all such patients. Copyright © 2022 Obstetrics, Gynecology and Reproduction. All rights reserved.

Von Willebrand Factor and Myeloperoxidase as Laboratory Predictive Markers of In-Hospital Survival in Severe COVID-19 Patients

Background. The severe acute respiratory syndrome of the SARS-CoV-2 virus-mediated coronavirus disease 2019 (COVID-19) highlighted the central role of immunothrombosis. Severe endothelial damage with the release of unusually large multimers of von Willebrand factor (vWF) and subsequent consumption of ADAMTS-13 is described during severe COVID-19. The activation of innate immune cells among which neutrophils contribute to the formation of extracellular neutrophil traps (NETs) and to the release of myeloperoxidase (MPO) potentially contributing to the spread of inflammation and microvascular thrombosis. Objective - to evaluate the ability of vWF, ADAMTS-13 and MPO to predict in-hospital mortality in severe COVID-19 patients needing mechanical ventilation. Methods. We performed a one-center observational study of 79 severe COVID-19 patients entering intensive care unit for mechanical ventilation, examining vWF, ADAMTS-13 and MPO among other potential predictors for in-hospital death. Results. After multivariate analysis, vWF antigen (vWF:Ag) and MPO antigen (MPO:Ag) were finally the single two parameters which increasing values were independently associated with non-survival;vWF:Ag (U/dL): adjusted OR 3.360, 95% CI 1.562-7.228, p = 0.0019;MPO:Ag (ng/ml): adjusted OR 1.062, 95% CI 1.024-1.101, p = 0.0011. From these results a simplified mortality score was derived and patients categorized as having a score value higher or lower that the median value of the score: a high score value was associated with a lower cumulative survival rate (p < 0.0001), 50% of the cases being dead at day 13 post-hospital admission. Conclusions. In severe COVID-19 necessitating mechanical ventilation, increasing values of MPO activity and of vWF antigen tested at admission are associated with poor survival. Copyright © 2022 Izdatel'stvo Meditsina. All rights reserved.

Pathogenetic and prognostic significance of inflammation and altered ADAMTS-13/vWF axis in patients with severe COVID-19

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.

Macrophage activation syndrome in COVID-19

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.

Features of nervous system damage in antiphospholipid syndrome

Antiphospholipid syndrome (APS) is an autoimmune process that increases the risk of arterial and venous thrombosis. The mechanism of damage to the central nervous system (CNS) can be not only due to thrombosis, but also antiphospholipid antibodies (APA) circulating in the peripheral blood. The latter can damage the cerebral vascular endothelium, alter the resistance of the blood-brain barrier and penetrate into the central nervous system, exerting a damaging effect on astroglia and neurons, as evidenced by the release of neurospecific proteins into the peripheral bloodstream. The role of APS in developing cerebral ischemia, migraine, epilepsy, chorea, transverse myelitis, multiple sclerosis, cognitive impairment and mental disorders, as well as the peripheral nervous system is described. It should also be noted about a role of APS for emerging neurological disorders in COVID-19, enabled apart from thrombogenesis due to APA via 2 potential mechanisms - molecular mimicry and neoepitope formation. Further study of the APS pathogenesis and interdisciplinary interaction are necessary to develop effective methods for patient management.

Antiviral activity of benzydamine hydrochloride against SARS-CoV-2 in vitro model

Due to the emergence of a new coronavirus infection COVID-19, scientists around the world are actively working on a vaccine against the SARS-CoV-2 coronavirus. At the same time, it is possible that existing medications can help in the fight against this disease. The local antiseptic drug benzidamine hydrochloride in the early stages of illness can prevent the virus from entering the lower respiratory tract and potentially reduce the severe illness associated with pneumonia and, as a result, reduce COVID-19-related hospitalizations, which can significantly reduce the burden on the health care system. The aim: to evaluate the antiviral activity of benzidamine hydrochloride against SARS-CoV-2 in vitro. Material and methods. Antiviral properties of benzidamine hydrochloride were studied in vitro in non-toxic concentrations on monolayer of Vero-E6 cells infected with pandemic strain of SARS-CoV-2 coronavirus in treatment and prophylactic scheme of the compound and virus administration. Results. Benzidamine hydrochloride has antiviral activity (15,0 mcg/ml), the efficiency of its antiviral action is directly proportional to the concentration of the substance. Conclusions. Taking into account very limited range of antiviral drugs with direct action on SARS-CoV-2 virus, the studied preparation can be used in complex therapy at early stages of the disease, which can prevent virus penetration into lower respiratory tract and potentially reduce the number of complications. © 2021, Numikom. All rights reserved.

Regarding the evidence-based use of micronized progesterone

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.

Septic shock

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.

Laboratory monitoring of COVID-19 patients and importance of coagulopathy markers

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.

Novel coronavirus infection (COVID-19) and risk groups in obstetrics and gynecology

Dear editors of Obstetrics, Gynecology and Reproduction Journal! Due to the particular urgency of the problem of managing patients with a new coronavirus infection (COVID-19), we are sending a letter outlining our position on this issue.

Coronavirus disease (COVID-19) and disseminated intravascular coagulation

COVID-19 is an infectious disease caused by the beta-coronavirus SARS-CoV-2 that in 2020 has spread worldwide. In most severe patients, the clinical picture begins with respiratory failure further deteriorating up to multiple organ failure. Development of coagulopathy is the most adverse prognostic. Analyzing currently available clinical data revealed that 71.4 % and 0.6 % of survivors and fatal cases, respectively, demonstrated signs of overt disseminated intravascular coagulation (DIC). Monitoring D-dimer level, prothrombin time, platelet count and fibrinogen content is important for determining indications for treatment and hospitalization in COVID-19 patients. In case such parameters deteriorate, a more pro-active “aggressive” intensive care should be applied. Low molecular weight heparin (LMWH) should be administered to all patients with diagnosed COVID-19 infection (including non-critical patients) requiring hospitalization, but having no contraindications to LMWH.

Pregnancy and Zika virus

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.