Fondaparinux Sodium: Recent Advances in the Management of Thrombosis.

Fondaparinux sodium is a chemically synthesized selective factor Xa inhibitor approved for the prevention and treatment of venous thromboembolic events, that is, deep vein thrombosis, pulmonary embolism, and superficial vein thrombosis, in acutely ill (including those affected by COVID-19 or cancer patients) and those undergoing surgeries. Since its approval in 2002, the efficacy and safety of fondaparinux is well demonstrated by many clinical studies, establishing the value of fondaparinux in clinical practice. Some of the advantages with fondaparinux are its chemical nature of synthesis, minimal risk of contamination, 100% absolute bioavailability subcutaneously, instant onset of action, a long half-life, direct renal excretion, fewer adverse reactions when compared with direct oral anticoagulants, and being an ideal alternative in conditions where oral anticoagulants are not approved for use or in patients intolerant to low molecular weight heparins (LMWH). In the last decade, the real-world use of fondaparinux has been explored in other conditions such as acute coronary syndromes, bariatric surgery, in patients developing vaccine-induced immune thrombotic thrombocytopenia (VITT) and in pregnant women with heparin-induced thrombocytopenia (HIT), or those intolerant to LMWH. The emerging data from these studies have culminated in recent updates in the guidelines that recommend the use of fondaparinux under various conditions. This paper aims to review the recent data and the subsequent updates in the recommendations of various guidelines on the use of fondaparinux sodium.

The Effectiveness of Bevacizumab in COVID-19 Pneumonia Among Critically Ill Patients

Background:Bevacizumab, an antiangiogenic drug, is being evaluated for the management of novel coronavirus disease (COVID-19) pneumonia among critically ill patients. The objective of this study was to assess the effectiveness of bevacizumab in severe COVID-19 pneumonia. Methods:This was a retrospective, observational study performed in 111 patients diagnosed with COVID-19 pneumonia. Bevacizumab was administered intravenously at 7.5 mg/kg along with standard care in a non-randomly selected subset of patients (n = 29) with evidence of acute respiratory distress syndrome (ARDS) within 72 hours of worsening of oxygenation. The primary outcome measure was intensive care unit (ICU)-related mortality. Results:Bevacizumab was administered for a median of 9.4 (4-24) days from the onset of symptoms and 2.2 (1-3) days from the day of ICU admission. Bevacizumab-treated patients showed a statistically significant improvement in PF ratio and reduction in radiological severity score. In the bevacizumab group, 13 (44.8%) of 29 patients died in ICU, and in the standard-of-care group, 37 (45.1%) of 82 patients died. The difference in clinical status assessed using the World Health Organization 7-category Ordinary Scale at 28 days between the bevacizumab group and the standard-of-care group was not statistically significant (odds ratio 1.02, 95% confidence interval 0.44-2.4, P = .94). Conclusion:Bevacizumab plus standard care was not superior to standard care alone in reducing mortality and improving clinical outcomes at day 28.

Characterising the treatment of thromboembolic events after COVID-19 vaccination in 4 European countries and the US: An international network cohort study.

Background: Thrombosis with thrombocytopenia syndrome (TTS) has been identified as a rare adverse event following some COVID-19 vaccines. Various guidelines have been issued on the treatment of TTS. We aimed to characterize the treatment of TTS and other thromboembolic events (venous thromboembolism (VTE), and arterial thromboembolism (ATE) after COVID-19 vaccination and compared to historical (pre-vaccination) data in Europe and the US. Methods: We conducted an international network cohort study using 8 primary care, outpatient, and inpatient databases from France, Germany, Netherlands, Spain, The United Kingdom, and The United States. We investigated treatment pathways after the diagnosis of TTS, VTE, or ATE for a pre-vaccination (background) cohort (01/2017-11/2020), and a vaccinated cohort of people followed for 28 days after a dose of any COVID-19 vaccine recorded from 12/2020 onwards). Results: Great variability was observed in the proportion of people treated (with any recommended therapy) across databases, both before and after vaccination. Most patients with TTS received heparins, platelet aggregation inhibitors, or direct Xa inhibitors. The majority of VTE patients (before and after vaccination) were first treated with heparins in inpatient settings and direct Xa inhibitors in outpatient settings. In ATE patients, treatments were also similar before and after vaccinations, with platelet aggregation inhibitors prescribed most frequently. Inpatient and claims data also showed substantial heparin use. Conclusion: TTS, VTE, and ATE after COVID-19 vaccination were treated similarly to background events. Heparin use post-vaccine TTS suggests most events were not identified as vaccine-induced thrombosis with thrombocytopenia by the treating clinicians.

A Mini-Review on Cardiovascular and Hematological Complications of COVID-19

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is named as the coronavirus disease of 2019 (COVID-19). Patients with SARS-CoV-2 infection experience a wide range of symptoms and they are at the risk of various systemic complications. Besides the pulmonary complications, COVID-19 cases may develop cardiovascular and hematological complications. This study aimed to review the most important hematological and cardiovascular complications caused by SARS-CoV-2 infection. Method(s): The English databases, including Pubmed, ScienceDirect, Cochrane Library, Scopus, and Google Scholar, were searched. The published papers were selected and reviewed based on the subject of this study. Result(s): The review of the literature showed that several cardiovascular complications related to COVID-19, including acute myocardial infarction, cardiomyopathy, acute heart failure, and venous thromboembolic events due to coagulation abnormalities, have been reported. COVID-19 associated hematological complications include elevated levels of hematological factors including C-reactive pro-tein, lactate dehydrogenase, procalcitonin, and ferritin. Furthermore, the levels of blood cells, including lymphocytes and thrombocytes, can be reduced. Conclusion(s): This study reviewed COVID-19-associated cardiovascular and hematopoietic complica-tions. In conclusion, the patients may experience a wide range of cardiovascular and hematological is-sues during the illness. These complications are often associated with the need for ICU support and care which imposes further costs to the healthcare system. So the healthcare team must consider the possible complications when treating COVID-19 patients to reduce the treatment costs and mortality of patients.Copyright © 2021 Bentham Science Publishers.

Association between thromboembolic events and COVID-19 infection within 30 days: a case-control study among a large sample of adult hospitalized patients in the United States, March 2020-June 2021.

The association between thromboembolic events (TE) and COVID-19 infection is not completely understood at the population level in the United States. We examined their association using a large US healthcare database. We analyzed data from the Premier Healthcare Database Special COVID-19 Release and conducted a case-control study. The study population consisted of men and non-pregnant women aged ≥ 18 years with (cases) or without (controls) an inpatient ICD-10-CM diagnosis of TE between 3/1/2020 and 6/30/2021. Using multivariable logistic regression, we assessed the association between TE occurrence and COVID-19 diagnosis, adjusting for demographic factors and comorbidities. Among 227,343 cases, 15.2% had a concurrent or prior COVID-19 diagnosis within 30 days of their index TE. Multivariable regression analysis showed a statistically significant association between a COVID-19 diagnosis and TE among cases when compared to controls (adjusted odds ratio [aOR] 1.75, 95% CI 1.72-1.78). The association was more substantial if a COVID-19 diagnosis occurred 1-30 days prior to index hospitalization (aOR 3.00, 95% CI 2.88-3.13) compared to the same encounter as the index hospitalization. Our findings suggest an increased risk of TE among persons within 30 days of being diagnosed COVID-19, highlighting the need for careful consideration of the thrombotic risk among COVID-19 patients, particularly during the first month following diagnosis.

Serious adverse event following immunization and thromboembolic events associated with COVID19 vaccination: An analysis of nationwide causality assessment from India.

BACKGROUND: Vaccines against the COVID-19 pandemic were introduced in late 2020. The present study has been conducted to study the serious Adverse Events Following Immunization (AEFIs) reported for COVID-19 vaccines from India. METHODS: Secondary data analysis of the causality assessment reports for the 1112 serious AEFIs published by the Ministry of Health & Family Welfare, Government of India, was conducted. For the current analysis, all the reports published till 29.03.2022 were included. The primary outcome variables analyzed were the consistent causal association and the thromboembolic events. RESULTS: The majority of the serious AEFIs assessed were either coincidental (578, 52%) or vaccine product related (218, 19.6%). All the serious AEFIs were reported among the Covishield (992, 89.2%) and COVAXIN (120, 10.8%) vaccines. Among these, 401 (36.1%) were deaths, and 711 (63.9%) were hospitalized and recovered. On adjusted analysis, females, the younger age group and non-fatal AEFIs showed a statistically significant consistent causal association with COVID-19 vaccination. Thromboembolic events were reported among 209 (18.8%) of the analyzed participants, with a significant association with higher age and case fatality rate. CONCLUSION: Deaths reported under serious AEFIs were found to have a relatively lower consistent causal relationship with the COVID-19 vaccines than the recovered hospitalizations in India. No consistent causal association was found between the thromboembolic events and the type of COVID-19 vaccine administered in India.

Comparison of coagulation profile and thromboembolic events among patients undergoing spinal surgery before and after COVID-19 pandemic.

BACKGROUND: Impairment of coagulation parameters and increased rate of thromboembolism are known complications of COVID-19 infection. In this study the coagulation profile and rate of thromboembolic events between two groups of patients who underwent spinal surgery before and after the COVID-19 pandemic was compared. PATIENTS AND METHOD: Clinically and laboratory negative for COVID-19 elective patients before (n: 211) and during COVID- 19 pandemic (n: 294) with spinal surgeries were included in this retrospective study. Surgical characteristics, Physiologic parameters, coagulation parameters and thromboembolic events were compared between the two study groups. RESULTS: Preoperative coagulation parameters, including PT, PTT, and INR were significantly increased during the COVID-19 pandemic (P < 0.001. P = 0.001, and P < 0.001, respectively), while the platelet count was significantly reduced (P = 0.04). The same differences were observed between the two study groups after the spinal surgery. In addition, respiratory rate and postoperative bleeding of the first postoperative 24 h was significantly more in patients who were operated on during COVID-19 outbreak (P = 0.03 and P = 0.002, respectively). The rate of thromboembolic events was 3.1% during the COVID-19 pandemic (seven PE, one DVT, and one MI) and 0% before that. This difference was statistically significant (P = 0.043). CONCLUSION: The rate of thromboembolic events seems to be increased during the COVID-19 pandemic. These findings urge more stringent monitoring of the patients' coagulation parameters during the COVID-19 outbreak.

Increased Reporting of Venous and Arterial Thromboembolic events reported with Tixagevimab-Cilgavimab for COVID-19.

OBJECTIVES: Since in two phase 3 clinical trials, there were a disproportion of number of thromboembolic events in the tixagevimab/cilgavimab group than in placebo group, there is a cardiovascular safety concerns with the use of this Anti-SARS-COV-2 Monoclonal Antibody. Whether tixagevimab/cilgavimab use in real life context increases the risk for of thromboembolic events is unclear. METHODS: We used VigiBase, the World Health Organization's individual case safety reports database, to assess the risk of reporting arterial or venous thromboembolic events in COVID-19 patients (≥12 years) exposed to tixagevimab/cilgavimab compared with COVID-19 patients exposed to other anti-SARS-CoV-2 mAbs, including casirivimab/imdevimab, bamlanivimab/etesevimab and sotrovimab. RESULTS: Among the 8,952 reports of patients with an anti-SARS-CoV-2 mAb, 31 reports of thromboembolic events associated with tixagevimab/cilgavimab, mainly deep vein thrombosis (10), pulmonary embolism (8) and myocardial infarction (7). Compared with other anti-SARS-CoV-2 mAbs, the use of tixagevimab/cilgavimab was associated with an increased risk of reporting arterial thromboembolic events (Reporting Odds Ratio (ROR) 3.25; 95%CI 1.73, 6.10). Concerning venous thromboembolic events, a significant increase in the risk of reporting was observed with use of tixagevimab/cilgavimab (ROR 3.59; 95%CI 2.16, 5.96). CONCLUSIONS: This observational study corroborate in a real-world setting, the cardiovascular safety signal already found with tixagevimab/cilgavimab in two clinical trials. Owing these thromboembolic safety concerns and considering the lack of clinical trials supporting a protection against the omicron variant, there is an urgent need to improve knowledge on the effectiveness of tixagevimab/cilgavimab with new COVID-19 variants.

The Efficacy and Safety of Prolonged Oral Anticoagulation for the Prevention of Thromboembolic Events in Patients Recovered From COVID-19 1 Year After Hospital Discharge: The SARCOV-19 Prospective Registry.

Our objective in this study is to know the predictors of thromboembolic events 1 year after hospitalization for severe COVID-19 and the benefit of preventive oral anticoagulation for 1 month to placebo after release. We conducted a prospective study to determine the benefit of preventive anticoagulation upon discharge from the hospital and to determine the predictive factors of thromboembolic events. We included 720 patients in the SARCOV-19 Registry, with a mean age of 62.07 (±18.11), and 61.1% male. After 1 year, 60 thromboembolic events were observed, 45 in patients on a placebo, and 15 in patients on a direct oral anticoagulant. The predictive factors determined for these events were the presence of cardiac disease, elevation of D-dimer during hospitalization, myocardial damage defined by elevation of troponins more than 6 times normal, and the use of mechanical ventilation. However, the use of preventive anticoagulation protects against thrombotic events and reduces the risk of a thromboembolic event at 1 year with a relative risk of 0.49 compared to a placebo. The prolongation of the preventive anticoagulation at the exit will protect with a decrease of almost 50% of the risk against thrombotic events and this without increasing the risk of bleeding.

An overview of prophylaxis and treatment indications for COVID-19-related thrombotic complications

In 2020, a coronavirus-related disease (COVID-19) became a pandemic. The disease was recognized as a viral respiratory illness caused by SARS-CoV-2. Histologic analysis of pulmonary vessels in severely affected patients revealed a microangio-pathic thrombosis. It was rapidly recognized that the disease could behave as a thrombotic disease, both in the venous and arterial circulations and affecting multiple organs. Anticoa-gulant treatments were immediately considered to prevent or control the underlying coagulopathy. The emergency of the situation and the limited knowledge in the early months accounted for variable success of the anticoagulation regi-mens. The benefit/bleeding risk ratio of anticoagulant treat-ments depended on the severity and evolution of the disease in different subgroups of patients. This review aims to provide a synthesized guide on how anticoagulant protocols indicated for the prophylaxis and treatment of COVID-19-related hyper -coagulable state have evolved and have been successfully adapted to specific scenarios throughout the pandemic.

Prophylaxis of Venous Thromboembolism in Patients Who Recovered from COVID-19

Background: Although COVID-19 has been mainly identified as a viral respiratory tract infection, studies have reported that severe COVID-19 is often complicated with coagulopathy resulting in high risk of venous thromboembolism (VTE) and mortality. In addition, COVID-19 has been regarded as a risk factor for thromboembolic events. Accumulating evidence indicates the necessity of diagnostic and prophylactic strategies against thromboembolic events in COVID-19. Currently, subcutaneous injectable drugs such as enoxaparin are widely used for prophylaxis of thromboembolic events. However, although these drugs are recommended to be used for 6 months, they are usually discontinued after 7-10 days because of administration difficulties. On the other hand, new generation anticoagulants are oral form of these drugs and can be safely used for a longer time. Since there is still not an indication of these drugs for the prophylaxis of thromboembolic events following COVID-19, they are not routinely used in clinical practice. Method(s): COVID-19 patients discharged from inpatient clinic between 01.06.2021 and 01.12.2021 were referred to our outpatient clinic due to regulation of anticoagulant medication. We administered new generation oral anticoagulants for prophylaxis against thromboembolic events in 50 patients. For this purpose, we used 30 mg 1x1 edoxaban, 15 mg 1x1 rivaroxaban or 2.5 mg 2x1 apixaban for 6 months. On the other hand, it was noticed from hospital medical records that 100 patients followed-up in inpatient clinic during that period received enoxaparin injections for 10 days during hospitalization and no further anticoagulant medication was given. short term or long term Results: In general, we obtained successful outcomes in patients who were administered oral anticoagulants.On the contrary, some of the patients who did not use these drugs developed thromboembolic events following COVID-19 disease. None of the patients receiving oral anticoagulants developed thromboembolic events during 6-month followup. On the other hand, among the patients who received enoxaparin injections, three patients developed venous thromboembolism(deep vein thrombosis in two patients and pulmonary embolism in one patient, all of them nearly one month later), and two patients arterial thromboembolism Method of prophylaxis Conclusion(s): We compared long-term oral anticoagulant medications and short term injections and found that thromboembolic events were not encountered in longterm oral medication. We suggest routine use of new anticoagulants as prophylactic agents against thromboembolic events following COVID-19 disease..

Pulmonary Embolism in Post-CoviD-19 Patients, a Literature Review: Red Flag for Increased Awareness?

Although COVID-19 was primarily considered a respiratory illness, rapidly accumulating data suggest that COVID-19 is associated with a high incidence of venous thromboembolic complications. The primary objective of this review article was to reveal whether we need to increase awareness of pulmonary embolism in the period following the COVID-19 infection given that the epidemiologic facts are still poor. A literature search and a critical review of the collected studies were conducted. An electronic search of PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EMBASE) from June 2020 until June 2022. The long-term health consequences of COVID-19 remain largely unclear. This review highlights the importance of awareness of the potentially increased incidence of venous thromboembolism in post-COVID-19 patients, even those with mild or asymptomatic disease. Further research is required to establish appropriate clinical management guidelines for the prevention of thromboembolic complications in the post-COVID-19 period.

Increased Susceptibility for Thromboembolic Events versus High Bleeding Risk Associated with COVID-19.

The infection with the SARS-CoV-2 virus is associated with numerous systemic involvements. Besides the severe respiratory injuries and cardiovascular complications, it became obvious early on that this disease carries an increased risk of thromboembolic events, but a higher propensity for bleedings as well. We researched the medical literature over significant PubMed published articles debating on the prevalence, category of patients, the moment of occurrence, and evolution of venous thromboembolism (VTE), but also of venous and arterial "in situ" thrombosis (AT), and hemorrhagic events as well. Most researchers agree on an increased prevalence of thromboembolic events, ranging between 25 and 31% for VTE, depending on the analyzed population. For AT and hemorrhagic complications lower rates were reported, namely, about 2-3%, respectively, between 4.8 and 8%, occurring mostly in older patients, suffering from moderate/severe forms of COVID-19, with associated comorbidities. It is important to mention that patients suffering from hemorrhages frequently received thromboprophylaxis with anticoagulant drugs. As a consequence of thromboembolic and hemorrhagic complications which are both important negative prognostic factors, the evolution of patients infected with the SARS-CoV-2 virus is aggravated, determining an augmented morbidity and mortality of this population.

Thromboembolic events and hemorrhagic stroke after mRNA (BNT162b2) and inactivated (CoronaVac) covid-19 vaccination: A self-controlled case series study.

Background: This study aims to evaluate the association between thromboembolic events and hemorrhagic stroke following BNT162b2 and CoronaVac vaccination. Methods: Patients with incident thromboembolic events or hemorrhagic stroke within 28 days of covid-19 vaccination or SARS-CoV-2 positive test during 23 February to 30 September 2021 were included. The incidence per 100,000 covid-19 vaccine doses administered and SARS-CoV-2 test positive cases were estimated. A modified self-controlled case series (SCCS) analysis using the data from the Hong Kong territory-wide electronic health and vaccination records. Seasonal effect was adjusted by month. Findings: A total of 5,526,547 doses of BNT162b2 and 3,146,741 doses of CoronaVac were administered. A total of 334 and 402 thromboembolic events, and 57 and 49 hemorrhagic stroke cases occurred within 28 days after BNT162b2 and CoronaVac vaccination, respectively. The crude incidence of thromboembolic events and hemorrhagic stroke per 100,000 doses administered for both covid-19 vaccines were smaller than that per 100,000 SARS-CoV-2 test positive cases. The modified SCCS detected an increased risk of hemorrhagic stroke in BNT162b2 14-27 days after first dose with adjusted IRR of 2.53 (95% CI 1.48-4.34), and 0-13 days after second dose with adjusted IRR 2.69 (95% CI 1.54-4.69). No statistically significant risk was observed for thromboembolic events for both vaccines. Interpretation: We detected a possible safety signal for hemorrhagic stroke following BNT162b2 vaccination. The incidence of thromboembolic event or hemorrhagic stroke following vaccination is lower than that among SARS-CoV-2 test positive cases; therefore, vaccination against covid-19 remains an important public health intervention. Funding: This study was funded by a research grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (reference COVID19F01).

[Coronavirus infection and risk of postoperative venous thromboembolic events]. / Koronavirusnaya infektsiya i risk posleoperatsionnykh venoznykh tromboembolicheskikh sobytii u khirurgicheskikh bol'nykh.

OBJECTIVE: To determine whether patients with perioperative or previous coronavirus infection (CVI) have a greater risk of venous thromboembolic events (VTE). MATERIAL AND METHODS: A multiple-center regional prospective retrospective cohort study included elective and emergency patients who underwent surgery in November 2020. The primary endpoint was VTE (PE/DVT) within 30 days after surgery. CVI was stratified as perioperative (7 days before surgery - 30 days after surgery), recent (1-6 weeks before surgery) and remote (≥7 weeks before surgery) infection. There was no information about prevention or preoperative anticoagulation at baseline data collection. RESULTS: Incidence of postoperative VTE was 1.5% (10/650) in patients without CVI, 33.3% (3/9) in patients with perioperative CVI, 18.1% (2/11) in patients with recent CVI and 8.3% (1/12) in patients with remote CVI. After adjusting the confounders, patients with perioperative and recent CVI remained at a higher risk of VTE. In general, VTEs were independently associated with 30-day mortality. In patients with CVI, mortality rate among ones without VTE was 21.7% (5/23), with VTE - 44.4% (4/9). CONCLUSION: Patients with perioperative CVI have a higher risk of postoperative VTE compared to those without CVI and patients with previous CVI and no residual symptoms. Mortality in this group is also higher than in other cohorts.

Real-Time Prediction of Mortality, Cardiac Arrest, and Thromboembolic Complications in Hospitalized Patients With COVID-19.

Background: COVID-19 infection carries significant morbidity and mortality. Current risk prediction for complications in COVID-19 is limited, and existing approaches fail to account for the dynamic course of the disease. Objectives: The purpose of this study was to develop and validate the COVID-HEART predictor, a novel continuously updating risk-prediction technology to forecast adverse events in hospitalized patients with COVID-19. Methods: Retrospective registry data from patients with severe acute respiratory syndrome coronavirus 2 infection admitted to 5 hospitals were used to train COVID-HEART to predict all-cause mortality/cardiac arrest (AM/CA) and imaging-confirmed thromboembolic events (TEs) (n = 2,550 and n = 1,854, respectively). To assess COVID-HEART's performance in the face of rapidly changing clinical treatment guidelines, an additional 1,100 and 796 patients, admitted after the completion of development data collection, were used for testing. Leave-hospital-out validation was performed. Results: Over 20 iterations of temporally divided testing, the mean area under the receiver operating characteristic curve were 0.917 (95% confidence interval [CI]: 0.916-0.919) and 0.757 (95% CI: 0.751-0.763) for prediction of AM/CA and TE, respectively. The interquartile ranges of median early warning times were 14 to 21 hours for AM/CA and 12 to 60 hours for TE. The mean area under the receiver operating characteristic curve for the left-out hospitals were 0.956 (95% CI: 0.936-0.976) and 0.781 (95% CI: 0.642-0.919) for prediction of AM/CA and TE, respectively. Conclusions: The continuously updating, fully interpretable COVID-HEART predictor accurately predicts AM/CA and TE within multiple time windows in hospitalized COVID-19 patients. In its current implementation, the predictor can facilitate practical, meaningful changes in patient triage and resource allocation by providing real-time risk scores for these outcomes. The potential utility of the predictor extends to COVID-19 patients after hospitalization and beyond COVID-19.

Major coagulation disorders and parameters in COVID-19 patients.

Coronavirus disease 2019 (COVID-19), with a high prevalence rate, has rapidly infected millions of people around the world. Since viral infections can disrupt the coagulation and homeostasis cascades, various inflammatory and coagulation problems occur due to COVID-19 infection, similar to coronavirus epidemics in 2003 and 2004. According to multiple previous studies, in the present research, we reviewed the most commonly reported problems of COVID-19 patients, such as venous thromboembolism, pulmonary embolism, disseminated intravascular coagulation, etc. and investigated the causes in these patients. Coagulation and inflammatory markers, such as platelets and fibrinogen, C-reactive protein, lactate dehydrogenase, d-dimer, prothrombin time, etc., were also discussed, and the treatment options were briefly reviewed. In addition to coagulation treatments, regular examination of coagulation parameters and thrombotic complications can be helpful in the timely treatment of patients. Therefore, it is helpful to review the coagulation problems in COVID-19 patients. Although all mentioned problems and markers are important in COVID-19, some of them are more valuable in terms of diagnosis and prognosis.

Calcium Signaling Pathway Is Involved in the Shedding of ACE2 Catalytic Ectodomain: New Insights for Clinical and Therapeutic Applications of ACE2 for COVID-19.

The angiotensin-converting enzyme 2 (ACE2) is a type I integral membrane that exists in two forms: the first is a transmembrane protein; the second is a soluble catalytic ectodomain of ACE2. The catalytic ectodomain of ACE2 undergoes shedding by a disintegrin and metalloproteinase domain-containing protein 17 (ADAM17), in which calmodulin mediates the calcium signaling pathway that is involved in ACE2 release, resulting in a soluble catalytic ectodomain of ACE2 that can be measured as soluble ACE2 plasma activity. The shedding of the ACE2 catalytic ectodomain plays a role in cardiac remodeling and endothelial dysfunction and is a predictor of all-cause mortality, including cardiovascular mortality. Moreover, considerable evidence supports that the ACE2 catalytic ectodomain is an essential entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Additionally, endotoxins and the pro-inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor-alpha (TNFα) all enhanced soluble catalytic ectodomain ACE2 shedding from the airway epithelia, suggesting that the shedding of ACE2 may represent a mechanism by which viral entry and infection may be controlled such as some types of betacoronavirus. In this regard, ACE2 plays an important role in inflammation and thrombotic response, and its down-regulation may aggravate COVID-19 via the renin-angiotensin system, including by promoting pathological changes in lung injury. Soluble forms of ACE2 have recently been shown to inhibit SARS-CoV-2 infection. Furthermore, given that vitamin D enhanced the shedding of ACE2, some studies reported that vitamin D treatment is associated with prognosis improvement in COVID-19. This is an updated review on the evidence, clinical, and therapeutic applications of ACE2 for COVID-19.

Approach to a child with pediatric inflammatory multisystem syndrome with covid-19 recommendations by the Polish pediatric society expert group update february 2021

Pediatric inflammatory multisystem syndrome associated with COVID-19 (PIMS) is a new entity, occurring in children and young adults, associated with the SARS-CoV-2 infection. The first cases of PIMS were found in Poland in May 2020. Since October 2020, a signi-ficant increase in this new disease incidence has been observed in Poland, reflecting the increased incidence of COVID-19 in the pediatric population. PIMS development results from dysregulation of the immune system occurring after ca. 4 weeks after the SARS-CoV-2 infection. Diagnosis is based on criteria: a set of clinical features (including fever and features of multiple organ damage) and elevated inflammatory markers, excluding other cau-ses. The most common complications involve the cardiovascular system: heart damage with decreased left ventricular ejection fraction, shock, and coronary artery abnormalities. Mortality is around 2%. Appropriate management, including vital functions support and immunomodulating treatment, allows for a quick recovery of the vast majority of patients. The following document is a guideline for the diagnostic and therapeutic management of children with suspected PIMS in Poland. © 2021, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.