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1.
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.

2.
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.

3.
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.

4.
Research and Practice in Thrombosis and Haemostasis ; 5(SUPPL 2), 2021.
Article in English | EMBASE | ID: covidwho-1509187

ABSTRACT

Background: High von Willebrand factor (VWF)/ADAMTS13 fraction might reflect endothelial dysfunction observed in serious COVID-19. Aims: 1) To compare VWF/ADAMTS13 fraction by care setting and explore correlation of this parameter with some routine blood parameters;2) To prospectively evaluate whether and to what extent variations in VWF/ADAMTS13 fraction can be predictive of fatalities. Methods: VWF/ADAMTS13 fraction were compared by care setting (Intensive Care Unit -ICU-vs. Medical Ward -MW-). The study included 22 and 52 patients admitted to ICU and MW, respectively. For 54 patients, we collected also a blood sample at an interval of five days from the first one and prospectively investigated relationship in dynamic changes between VWF/ADAMTS13 fraction and routine blood parameters. Continuous variables were reported as median (IQR). Parametric and non-parametric tests were used according to value distribution and χ2 test to compare variables in a contingency table. The Area-Under-Curve (AUC) was calculated. The p values < 0.05 set the statistical significance. Results: Patients admitted to the ICU were significantly younger [63.0 (15.2) vs. 69.0 (19.7), P = 0.03 ] and mostly males (M/F: 17/5 vs. 26/29). Fatalities were similar in the two care settings (45.5% in ICU vs. 30.7% in MW, Fisher's Test: P = 0.19). Moreover, VWF:RCo/ ADAMTS13 fraction of 5.7 was predictive of ICU admission [AUC = 0.81 (0.70-0.92), p<0.001 ]. Overall, at admission, VWF:RCo/ ADAMTS13 fraction directly correlated with C-reactive protein (CRP) (Spearman r: 0.51, P < 0.0001 ). This relationship was observed also in the prospective cohort ( n = 54) (Spearman r: 0.54, P = 0.0014 ) and independently of the care setting (in ICU: P = 0.006 in MW: P = 0.02 ) and was maintained throughout the entire period of hospitalization. Cut-off of 6.5 in VWF:RCo/ADAMTS13 was associated with in-hospital death (AUC: 0.71, P = 0.003 ). Conclusions: VWF:RCo/ADAMTS13 fraction seems to be a good predictor of ICU admission and in-hospital mortality. This study also shows that during COVID-19, CRP directly correlates with endothelial dysfunction.

5.
Research and Practice in Thrombosis and Haemostasis ; 5(SUPPL 2), 2021.
Article in English | EMBASE | ID: covidwho-1508976

ABSTRACT

Background : COVID-19 (Coronavirus Disease 2019) is associated with High rates of thrombosis in hospitalized patients leading to varying pharmacologic thromboprophylaxis use based on rapidly changing societal guidance, institutional protocols from local expertise, and geographic patterns of practice. Aims : To assess the efficacy and safety of enoxaparin in hospitalized patients with moderate to severe COVID-19 infection. Methods : Phase II single-arm interventional prospective study including all patients treated with the study drug and an observational prospective cohort study including all patients screened for receiving the study drug but not included in the phase II study. Each patient was followed-up for a minimum of 90 days after COVID19 diagnosis. Patients included in the interventional study received subcutaneous enoxaparin in a single daily dose of:60 mg once daily in case of body weight of 45 to 60 kg 80 mg per day in case of weight from 61 to 100 kg or 100 mg once daily in case of bodyweight >100 kg for 14 days, with dose adjustments on the basis of anti-factor Xa activity monitoring. Patients included in the observational cohort received standard thrombo-prophylaxis with subcutaneous enoxaparin 40 mg/die. Primary outcomes were all-cause in-hospital 30-day and 90 mortality rates. Secondary outcomes were the proportion of patients in the severe or critical stage of disease at the end of treatment, proportion of patients who developed major and non-major bleeding events and thromboembolic complications, time to first negative RT-PCR on nasofaringeal swab, reduction of viral load in blood. Results : Recruitment of 100 patients enrolled phase II single-arm interventional prospective study has been completed, while the recruitment of 200 patients in the observational prospective cohort study is ongoing. Conclusions : Full results will be available by June 2021.

6.
Eur Rev Med Pharmacol Sci ; 25(10): 3886-3897, 2021 May.
Article in English | MEDLINE | ID: covidwho-1264765

ABSTRACT

OBJECTIVE: Platelets, blood coagulation along with fibrinolysis are greatly involved in the pathophysiology of infectious diseases induced by bacteria, parasites and virus. This phenomenon is not surprising since both the innate immunity and the hemostatic systems are two ancestral mechanisms which closely cooperate favoring host's defense against foreign invaders. However, the excessive response of these systems may be dangerous for the host itself. MATERIALS AND METHODS: We searched and retrieved the articles, using the following electronic database: MedLine and Embase. We limited our search to articles published in English, but no restrictions in terms of article type, publication year, and geography were adopted. RESULTS: The hemostatic phenotype of the infectious diseases is variable depending on the points of attack of the different involved pathogens. Infectious diseases which show a prothrombotic phenotype are bacterial sepsis, SARS-CoV-2 and malaria. However, among the bacterial sepsis, Yersinia Pestis is characterized by a profibrinolytic behavior. On the contrary, the hemorrhagic fevers, due to Dengue and Ebola virus, mainly exploit the activation of fibrinolysis secondary to a huge endothelial damage which can release a large amount of t-PA in the early phase of the diseases. CONCLUSIONS: Blood coagulation and fibrinolysis are greatly activated based on the strategy of the different infectious agents which exploit the excess of response of both systems to achieve the greatest possible virulence.


Subject(s)
Blood Coagulation , COVID-19/pathology , Fibrinolysis , COVID-19/complications , COVID-19/virology , Endothelial Cells/cytology , Endothelial Cells/metabolism , Endothelial Cells/virology , Erythrocytes/cytology , Erythrocytes/metabolism , Erythrocytes/parasitology , Humans , Monocytes/cytology , Monocytes/metabolism , Monocytes/virology , SARS-CoV-2/isolation & purification , Thromboplastin/metabolism , Viruses/pathogenicity
7.
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
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