Thrombosis In COVID-19 Research Articles

302. Using Antiphospholipid Antibody Presence as an Additional Biomarker to Identify COVID-19 Positive Patients with High Risk for Thrombosis

BackgroundPatients who are hospitalized with Coronavirus 2019 (COVID-19) are known to have increased risk for thrombosis. Several mechanisms have been proposed for increased thrombogenesis, including antiphospholipid antibodies (APLs). We sought to better understand the relationship between a commonly used marker of thrombosis, D-dimer, and antiphospholipid antibodies in relation to thrombosis in COVID-19. MethodsThis was a single-center prospective cohort study. Participants were adults admitted to the hospital with COVID-19 between March and December of 2020. Included patients required a positive COVID-19 nasopharyngeal nucleic acid amplification testing (NAAT), coagulation studies, and regular assessment of D-dimer levels. Patients who were excluded were pregnant adults, use of oral anticoagulants prior to admission, and absence of a positive COVID-19 nasopharyngeal NAAT. We tested 52 patients for antiphospholipid antibodies (APLs), including lupus anticoagulant (LA), anti-beta-2 glycoprotein antibodies (B2GP), and anti-cardiolipin antibodies (aCL). The endpoint for analysis was hospital discharge or development of a confirmed thrombosis. ResultsTwenty-nine of fifty-two patients (55.7%) with COVID-19 had non-negative APLs. Of these patients, twenty-seven (93.1%) had non-negative aCLs, the majority of which were IgM antibodies. There was a total of 7 thrombotic events in our cohort. The sensitivity of D-dimer alone was 85% and the sensitivity of APLs alone was 71%. In patients with an intermediate D-dimer level (i.e., greater than 2 milligrams per liter (mg/L) but less than 5 mg/L), the addition of non-negative APLs increased the sensitivity of D-dimer to 100%. In patients with a high D-dimer (i.e., greater than 5), the combined sensitivity of D-dimer and APLs was 60%. Out of the 7 thrombotic events in our cohort, two patients had negative APLs, however both patients had a D-dimer of greater than 5 mg/L. ConclusionThe use of APLs can assist in risk-stratifying patients in an intermediate-risk D-dimer group to consider prophylactic anticoagulation if APLs are negative and to consider therapeutic anticoagulation if APLs are non-negative. In the high-risk group (i.e., a D-dimer greater than 5 mg/dL), a therapeutic anticoagulation approach may be more appropriate. Disclosures All Authors: No reported disclosures

Evolution and transformation of JVS-CIT

Evolution and transformation of JVS-CIT

High levels of Von Willebrand factor markers in COVID-19: a systematic review and meta-analysis.

The SARS-CoV-2 virus has spread to all corners of the world. Thrombosis is the cause of organ failure and subsequent death in COVID-19. The pathophysiology of thrombosis in COVID-19 needs to be further explored to shed light on its downside. For this reason, this meta-analysis of Von Willebrand Factor profile (VWF: Ag, VWF: activity, VWF: RCo), ADAMTS-13, and factor VIII levels in COVID-19 was performed. To obtain data on the status of the aforementioned hemostatic factors, a systematic literature review and meta-analysis were performed on COVID-19. After reviewing the evaluation of 348 papers, 28 papers included in the meta-analysis, which was performed using STATA. The analysis showed an increase in VWF: Ag levels in COVID‐19 patients. VWF: Ac was higher in all COVID-19 patients, while it was lower in the COVID‐19 ICU patients. The pooled mean of VWF: RCO in all patients with COVID-19 was 307.94%. In subgroup analysis, VWF: RCO was significantly higher in ICU patients than in all COVID-19 patients. The pooled mean of ADAMTS-13 activity was 62.47%, and 58.42% in ICU patients. The pooled mean of factor VIII level was 275.8%, which was significantly higher in ICU patients with COVID-19 than all patients with COVID-19. Levels of VWF: Ag, VWF: activity, VWF: ristocetin, and factor VIII are increased in patients with COVID-19. The elevated levels in ICU patients with COVID-19 suggest that these markers may have prognostic value in determining the severity of COVID-19. New therapeutic programs can be developed as a result.

Biomarkers for Thrombosis in COVID-19: A Role for High Sensitivity Troponin-I and Immature Platelet Fraction?

Biomarkers for Thrombosis in COVID-19: A Role for High Sensitivity Troponin-I and Immature Platelet Fraction?IntroductionCoronavirus disease 2019 (COVID-19) is associated with increased risk of thrombosis with both venous and arterial thromboembolism observed. While d-dimer elevation has been shown to be associated with thrombosis, this elevation is present in over 50% of COVID-19 infections demonstrating a clear need for more specific biomarkers of thrombosis in this population. While there are a variety of theories to explain the increased risk for thrombosis: all center on Virchow's triad, specifically hypercoagulability and inflammation. Platelets play a significant role in hypercoagulability. Immature platelets, which are thought to be hyper-reactive, may specifically be associated with thrombosis in COVID-19. It would thus be reasonable to expect immature platelet fraction (IPF) and immature platelet count (IPC) to be predictive biomarkers of thrombosis in this population. Beyond hypercoagulability, High-Sensitivity (HS) Cardiac troponin-I can be a biomarker of inflammation and may also be predictive of thrombotic events in COVID-19. The aim of this study was to evaluate the relationship between IPF, IPC, HS cardiac troponin-I and thrombotic events in COVID-19.MethodsUsing a single center COVID-19 data registry, we extracted all patients with COVID-19 at our single center between May 1, 2020 and January 1, 2021. Patients were stratified into two groups based on thrombotic events during hospitalization, the thrombosis and no thrombosis groups. Biomarker values, including IPF, IPC, platelet counts, d-dimer, and HS cardiac troponin I were extracted. Two-sided Wilcoxon rank test was conducted to test group differences in IPF, IPC, platelet, d-dimer, and HS cardiac troponin-I values.ResultsThere were no significant differences in measurements of IPF at admission, peak IPF , platelet count at admission, peak platelet count, IPC at admission, and peak IPC between the thrombosis and no thrombosis groups. Minimum platelet count values were significantly lower in the thrombosis group compared to the no thrombosis group. D-dimer and troponin values were significantly higher in the thrombosis group than the no thrombosis group. (Table 1)DiscussionTo our knowledge this is the first study assessing the relationship between IPF, IPC, HS cardiac troponin-I and thrombosis in COVID-19. HS cardiac troponin did appear to be a predictive biomarker for thrombosis in COVID-19. This may be related to vascular inflammation playing a significant role in thrombosis. It may also be secondary to myocardial inflammation associated with severe disease in COVID-19.3 Patients with more severe disease are more prone to thrombosis. Unsurprisingly, our study corroborates evidence in the literature that d-dimer is associated with thrombotic events in COVID-19. On the other hand, IPF and IPC do not appear to be predictive biomarkers for thrombosis in this cohort. This appears consistent with the limited data assessing the relationship between IPF, IPC, and thrombosis outside of COVID-19. This does not dispel the importance of immature platelets in COVID-19, however. IPF and IPC are increased in patients with COVID-19, and our published data indicates they are predictors of COVID-19 severity. However, the relationship between immature platelets and outcomes in acute illness can be complex, as in sepsis, where the trend of IPC is associated with mortality, rather than the initial value. Future studies should delineate the relationship between trends in IPF or IPC and outcomes in COVID-19. Furthermore, it is crucial to define biomarkers of thrombosis and disease severity and mortality in COVID-19 which can potentially guide therapeutic interventions. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Thrombocytopenia with and without Thrombosis Following COVID-19 Vaccination

Introduction: Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) were rapidly developed during the COVID-19 pandemic. There is emerging evidence of adverse hematologic effects including thrombocytopenia, for recipients of both mRNA and adenovirus-vector vaccines. We report findings in 9 patients diagnosed with thrombocytopenia following administration of an approved COVID-19 vaccine and managed according to the ASH COVID-19 Thrombosis with Thrombocytopenia Syndrome (TTS) recommendations [https://www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia].Methods: The study population included adults >18 years of age presenting to a large Canadian tertiary care centre, between April 1 st, 2021 and May 31 st, 2021, with new-onset thrombocytopenia within 31 days of receiving COVID-19 vaccination. Vaccines approved during this time period in Canada included BNT162b2 (Pfizer-BioNTech, mRNA) vaccine, mRNA-1273 (Moderna, mRNA) vaccine, and ChAdOx1-S (AstraZeneca (AZ), adenovirus vector-based) vaccine. We report on the initial presentation, management and 90-day outcomes.Results: Among 9 patients with thrombocytopenia included in this cohort, the median age was 55 years (range 24 to 73), and 5 patients (56%) were female. Seven patients received AZ and 2 had Pfizer vaccines. All events occurred after the first dose of COVID-19 vaccine with a median of 11 days between vaccination and presentation to hospital (range 2 to 31). All patients admitted to hospital tested negative for COVID-19 by PCR.Four patients developed TTS, as confirmed on both HIT ELISA and serotonin release assay, following AZ vaccination. Two patients presented with headaches and were diagnosed with cerebral vein thrombosis (CVT); and 2 presented with dyspnea and were diagnosed with venous thromboembolism (VTE). Platelet counts at presentation ranged 14-136 and D-dimer ranged 4000 to >44,000. HIT ELISA optical densities were persistently elevated. Three patients were admitted to hospital and received non-heparin parenteral anticoagulation, IVIG, and steroids. One patient had refractory thrombocytopenia with extension of CVT prompting use of therapeutic plasma exchange. Two patients had recurrent thrombocytopenia within 30 days of discharge and responded to repeat IVIG treatment.Five patients developed immune thrombocytopenic purpura (ITP), four without associated thrombosis and one patient with history of ITP and splenectomy, maintained on Revolade, presented with ITP flare and deep vein thrombosis. Presenting complaints included petechial rash and minor bleeding such as epistaxis. Platelet counts ranged from undetectable to 67; D-dimer levels were normal in all at presentation. Four patients were admitted to hospital and received IVIG +/- steroids. Two patients had recurrent severe thrombocytopenia within 14 days of discharge, requiring repeat steroid pulse. See Table for summary of all patients.Conclusion: In summary, application of the ASH TTS guidance to patients presenting with thrombocytopenia, with and without thrombosis, following COVID-19 vaccination was instrumental in the early identification and successful management of these complications. [Display omitted] DisclosuresCarrier: Sanofi: Honoraria; Pfizer: Honoraria, Research Funding; Servier: Honoraria; Bayer: Honoraria; Leo Pharma: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Le Gal: BMS: Honoraria; Aspen: Honoraria; Bayer: Honoraria; LEO Pharma: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria. Castellucci: BMS: Honoraria; Pfizer: Honoraria; Amag Pharmaceuticals: Honoraria; The Academy: Honoraria.

Venous Thromboembolism in COVID-19 Compared to Non-COVID-19 Cohorts: A Systematic Review with Meta-Analysis

Background: A high incidence of venous thromboembolism (VTE) is reported in hospitalized COVID-19 patients, in particular in patients admitted to the intensive care unit (ICU). In patients with respiratory tract infections, including influenza A (H1N1), many studies have demonstrated an increased incidence of thromboses, but evidence is lacking regarding the risk difference (RD) of the occurrence of VTE between COVID-19 and non-COVID-19 patients. Methods: In this systematic review with meta-analysis, we evaluated the RD of the occurrence of VTE, pulmonary embolism (PE), and deep venous thrombosis (DVT) between COVID-19 and other pulmonary infection cohorts, in particular H1N1, and in an ICU setting. We searched for all studies comparing COVID-19 vs. non-COVID-19 regarding VTE, PE, and DVT. Results: The systematic review included 12 studies and 1,013,495 patients. The RD for VTE in COVID-19 compared to non-COVID-19 patients was 0.06 (95% CI 0.11–0.25, p = 0.011, I2 = 97%), and 0.16 in ICU (95% CI 0.045–0.27, p = 0.006, I2 = 80%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.03 (95% CI, 0.006–0.045, p = 0.01, I2 = 89%). The RD for PE between COVID-19 and non-COVID-19 patients was 0.021 in retrospective studies (95% CI 0.00–0.04, p = 0.048, I2 = 92%) and 0.11 in ICU studies (95% CI 0.06–0.16, p < 0.001, I2 = 0%). Conclusions: The growing awareness and understanding of a massive inflammatory response combined with a hypercoagulable state that predisposes patients to thrombosis in COVID-19, in particular in the ICU, may contribute to a more appropriate strategy of prevention and earlier detection of the thrombotic events.

The use of combined hormonal contraception in the context of the COVID-19 pandemic

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) was declared the cause of a global pandemic in early 2020. Patients with COVID-19 are at high risk for thrombotic occlusions of the arteries and veins. There are many ways that explain the high risk of thrombosis in COVID-19, they are conditionally divided into two main categories: mechanisms in which the renin-angiotensinaldosterone system is involved and mechanisms that affect the regulation of the immune response. It is assumed that the uncomplicated course of the disease is characterized by endothelial dysfunction, but if the process progresses with a pronounced immune response, plasma coagulation factors may also be involved, which significantly increases the risks of thromboembolic complications. The use of combined hormonal contraception (CHC) in the current conditions raises a number of concerns. According to some researchers, disorders of the hemostasis system observed in patients with COVID-19 may worsen while taking CHC and increase the risk of thromboembolic complications, which is especially important in severe disease with prolonged immobilization. However, with the use of CHC, the increase in thrombotic risks is explained primarily by changes in the plasma component of the hemostasis sys tem. At first glance, the recommendations to stop hormone therapy with confirmed COVID-19 seem logical, but they are based only on the procoagulant activity of estrogens, and not on real evidence. In patients with COVID-19, the increase in coagulation is associ ated with massive damage to the vascular endothelium (the so-called «external» coagulation pathway) and the immune response, and not with a primary increase in the level of coagulation factors per se. At the same time, stopping the intake of estrogens deprives the patient of their important protective effect. Thus, it became necessary to develop clinical guidelines for the management of women using contraception in the context of the COVID-19 pandemic.

Atypical visual impairment associated to cerebral sinus stenosis related to COVID-19 thrombosis

Cerebralvenoussinus stenosis (CVSS) may further complicate cerebral venous thrombosis(CVT) which is a rare thromboembolic complications in COVID-19 patients. We report a case of post COVID 19 CVT-related CVSS associated to intracranial hypertension (ICH). We discuss the possible mechanisms of highly asymmetric visual repercussions of ICH.

Fatal pulmonary thromboembolism in asymptomatic COVID-19

BackgroundCoronavirus disease 2019 (COVID-19) has claimed the lives of millions of people globally.AimsThis study aims to identify the pathological findings at autopsy of asymptomatic COVID-19 death, to compare the incidence of acute bilateral pulmonary thromboembolism (ABPTE) in asymptomatic COVID-19 deaths versus non-COVID-19 deaths and to explore the possible pathogenesis of thrombosis in COVID-19. We also consider the place of COVID-19 in the death certification of 4 cases who died from ABPTE.MethodsThis study primarily reviewed post-mortem reports of 6 asymptomatic COVID-19 deaths. Post-mortem reports for the years 2019 and 2020 were also reviewed to establish the incidence of ABPTE. Each post-mortem report was reviewed for gross examination, histology and toxicology findings. A literature review on COVID-19 autopsy findings, COVID-19 pathogenesis, thrombosis in COVID-19 and asymptomatic SARS-CoV-2 infection was also conducted using PubMed.ResultsOf the 6 asymptomatic COVID-19 deaths, 4 died as a result of ABPTE, 1 died of ischaemic and hypertensive cardiac disease caused by coronary artery disease and ventricular hypertrophy and the remaining case died of heart failure due to dilated cardiomyopathy caused by subendocardial fibrosis. There were 2 cases of bilateral pulmonary thromboembolism (BPTE) in 2019 out of 140 post-mortems. Excluding the 4 cases of ABPTE described already, there was 1 case of ABPTE in 2020 out of 156 post-mortems. A literature review on the pathogenesis of thrombosis in COVID-19 highlighted the significant role that the endothelium plays.ConclusionsMassive pulmonary thromboembolism may be a significant cause of death in asymptomatic COVID-19 infection.

Abstract MP03: Histone-mediated Platelet Activation And Microvesicle-induced Thrombin Generation In COVID-19

Background: Severe COVID-19 leads to inflammation and coagulopathy with progression to multiple organ failure. Several prothrombotic mechanisms have been proposed, including NETosis with release of citrullinated histones, platelet hyperactivation, and generation of procoagulant microvesicles. Aims: We hypothesized that histones derived from NETosis promote platelet activation and release of microvesicles that mechanistically contribute to thrombin generation and thrombosis in COVID-19. Methods: Platelet poor plasma (PPP) was prepared from 136 COVID-19 patients enrolled in a multicenter randomized clinical trial comparing standard prophylactic dose to intermediate dose enoxaparin in hospitalized patients with COVID-19 (NCT04360824). We also prepared PPP and washed platelets from 53 healthy subjects. We measured citrullinated histone H3 (H3Cit) by ELISA, microvesicles by flow cytometry, and thrombin generation using the Calibrated Automated Thrombogram. Ex vivo platelet adhesion and thrombus growth on collagen was measured in a microfluidic chamber. Results: Compared to healthy subjects, COVID-19 patients had elevated plasma levels of H3Cit and platelet-derived microvesicles. When PPP was triggered with exogenous tissue factor and phospholipids, higher endogenous thrombin potential, peak thrombin, and velocity index were observed in COVID-19 patients compared to healthy subjects. Increased thrombin generation with COVID-19 PPP was evident even when triggered without added phospholipids, suggesting the presence of procoagulant microvesicles in COVID-19 plasma. Enhanced thrombin generation also was observed after transfer of microvesicles isolated from COVID-19 patient plasma to control PPP. Incubation of control platelets with PPP from COVID-19 patients but not healthy subjects caused increased platelet-dependent thrombin generation and larger platelet-thrombi under venous shear stress. These effects of COVID-19 plasma on platelet-dependent thrombin generation and platelet-thrombi formation were inhibited by a histone aptamer. Conclusions: We conclude that histone-mediated platelet activation promotes thrombosis in COVID-19 in part via increased thrombin generation driven by microvesicles.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial

BackgroundThe devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis.DesignThis study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria.SummaryThe MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1

Incidence of Thrombotic Complications in COVID-19: On Behalf of ICODE: The International COVID-19 Thrombosis Biomarkers Colloquium

High rates of both venous and arterial thromboembolic events were observed early during the global COVID-19 pandemic, with severity of illness and need for intensive care unit admission correlating with increased thrombotic risk.

Anti-Phospholipid Antibodies and COVID-19 Thrombosis: A Co-Star, Not a Supporting Actor.

Background: COVID-19 clinical features include a hypercoagulable state that resembles the antiphospholipid syndrome (APS), a disease characterized by thrombosis and presence of antiphospholipid antibodies (aPL). The relationship between aPL-presence and the appearance of thrombi as well as the transience or permanence of aPL in COVID-19 patients is not sufficiently clear. Methods: A group of 360 COVID-19 patients were followed-up for 6 months. Classic aPL, anti-B2GPI IgA, anti-phosphatidylserine/prothrombin IgG/M and anti-SARS-CoV-2 antibodies were determined at acute phase and >12 weeks later. The reference group included 143 healthy volunteers of the same age-range distribution. Results: aPL prevalence was similar in COVID-19 patients and the reference population. aPL presence in both determinations was significantly associated with thrombosis (OR: 2.33 and 3.71), strong agreement being found for classic aPL and anti-B2GPI IgA (Weighted kappa: 0.85–0.91). Thrombosis-associated aPL occurred a median of 17 days after hospital admission (IQR: 6–28) vs. 4 days for the rest (IQR: 3–7). Although anti-SARS-CoV-2 antibodies levels increased during convalescence, aPL hardly changed. Conclusions: Most COVID-19 patients would carry these aPL before the infection. At least two mechanisms could be behind thrombosis, early immune-dysregulation-mediated thrombosis after infection and belated-aPL-mediated thrombosis, with SARS-CoV-2 behaving as a second hit.

Catheter directed thrombolysis for acute deep vein and arterial thrombosis in COVID-19: report of two cases from Sulaymaniyah, Kurdistan-Iraq

Abstract &#x0D; As one year elapsed since COVID-19 outbreak, venous and arterial thromboses are increasingly reported in different vascular territories. Once accessed by the virus, the endothelial cells, abundant in angiotensin converting enzyme-2 (ACE-2) protein, will be activated by the inflammatory process leading to coagulopathy and vascular lesions. Herein, we describe a case of extensive thrombosis of the infra-renal inferior vena cava and iliac femoral vein in a man of 62 and a case of acute superficial femoral artery thrombosis in a lady of 55. Both were COVID-19 confirmed cases with severe pneumonia, high D-Dimer levels and risk factors for severe disease or death. Despite presentation 1-2 weeks after the onset of thromboses, they were successfully managed by catheter directed thrombolysis (CDT) using tissue plasminogen activator (tPA). Owing to the increased morbidity and mortality of vascular thrombosis, there is a need to identify COVID-19 patients who need prophylaxis and prescribe them the right prophylactic drug (s). The excellent outcome of CDT in these two patients, from Sulaymaniyah/Iraq, supports the use of this treatment modality as a valid, safe and effective option for acute arterial and venous thromboses.&#x0D;

Hypercoagulability and thrombosis in COVID-19: a modifiable cause for mortality?

Hypercoagulability and thrombosis in COVID-19: a modifiable cause for mortality?

Pulmonary Thrombosis and Thromboembolism in COVID-19.

COVID-19, the disease responsible for the devastating pandemic that began at the end of 2019, has been associated with a significantly increased risk of pulmonary thrombosis, even in patients receiving prophylactic anticoagulation. The predilection for thrombosis in COVID-19 may be driven by at least two distinct, but interrelated, processes: a hypercoagulable state responsible for large-vessel thrombosis and thromboembolism and direct vascular and endothelial injury responsible for in situ microvascular thrombosis. The presence of pulmonary thrombosis may explain why hypoxemia is out of proportion to impairment in lung compliance in some patients with COVID-19 pneumonia. Because pulmonary embolism (PE) and COVID-19 pneumonia share many signs and symptoms, diagnosing PE in patients with COVID-19 can be challenging. Given the high mortality and morbidity associated with severe COVID-19 and the concern that aspects of the disease may be driven by thrombosis, many hospital systems have instituted aggressive anticoagulation protocols above standard VTE prophylaxis. In this review, the epidemiologic and pathophysiologic features, diagnosis, and treatment of COVID-19 pulmonary thrombosis and thromboembolism are discussed.

Low-Grade Endotoxemia and Thrombosis in COVID-19.

INTRODUCTION:Patients with community-acquired pneumonia display enhanced levels of lipopolysaccharides (LPS) compared with controls, suggesting that low-grade endotoxemia may be implicated in vascular disturbances. It is unknown whether this occurs in patients with coronavirus 2019 (COVID-19) and its impact on thrombotic complications.METHODS:We measured serum levels of zonulin, a marker of gut permeability, LPS, and D-dimer in 81 patients with COVID-19 and 81 healthy subjects; the occurrence of thrombotic events in COVID-19 during the intrahospital stay was registered.RESULTS:Serum LPS and zonulin were higher in patients with COVID-19 than in control subjects and, in COVID-19, significantly correlated (R = 0.513; P < 0.001). Among the 81 patients with COVID-19, 11 (14%) experienced thrombotic events in the arterial (n = 5) and venous circulation (n = 6) during a median follow-up of 18 days (interquartile range 11–27 days). A logistic regression analysis showed that LPS (P = 0.024) and D-dimer (P = 0.041) independently predicted thrombotic events.DISCUSSION:The study reports that low-grade endotoxemia is detectable in patients with COVID-19 and is associated with thrombotic events. The coexistence of low-grade endotoxemia with enhanced levels of zonulin may suggest enhanced gut permeability as an underlying mechanism.

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19.

Previous studies have shown that COVID-19 leads to thrombotic complications, which have been associated with high morbidity and mortality rates. Neutrophils are the largest population of white blood cells and play a pivotal role in innate immunity. During an infection, neutrophils migrate from circulation to the infection site, contributing to killing pathogens. This mechanism is regulated by chemokines such as IL-8. Moreover, it was shown that neutrophils play an important role in thromboinflammation. Through a diverse repertoire of mechanisms, neutrophils, apart from directly killing pathogens, are able to activate the formation of thrombi. In COVID-19 patients, neutrophil activation promotes neutrophil extracellular trap (NET) formation, platelet aggregation, and cell damage. Furthermore, neutrophils participate in the pathogenesis of endothelitis. Overall, this review summarizes recent progress in research on the pathogenesis of COVID-19, highlighting the role of the prothrombotic action of neutrophils in NET formation.

THROMBOSIS OF THE LEFT ILIAC ARTERY IN COVID-19: A CLINICAL CASE

The incidence of arterial thrombosis in patients with COVID-19 is about 11 %. Currently, the pathogenesis of these complications has not been fully studied. Purpose: present the course of COVID-19 Associated thrombosis of the left iliac artery on a clinical example. Material and methods. Patient with Covid-19 developed thrombosis the iliac artery. Results. A clinical example demonstrates that a patient with risk factors - coronary heart disease, type 2 diabetes mellitus, obesity, smoking, against the background of a new coronavirus infection, an iliac artery thromboembolism developed. Conservative treatment of thrombosis with antithrombotic drugs was not successful. In this connection, the patient was hospitalized in a socialized medical institution, where a thromboectomy was performed from the iliac, femoral, popliteal artery on the right. The patient's condition improved during the therapy. However, on the 3rd day, a pneumonia clinic developed, which was the reason for transferring him to a covid hospital. Despite the etiotropic and antithrombotic therapy, repeated arterial thrombosis of the vessels of the lower limb progressed, which required surgical intervention (amputation of the lower leg). The cause of death of the patient was a progressive multiple organ. A clinical example shows that the pathogenesis of thrombosis in COVID-19 has not been fully studied (not established), and treatment regimens with antithrombotic drugs require further revision.

A network-informed analysis of SARS-CoV-2 and hemophagocytic lymphohistiocytosis genes' interactions points to Neutrophil extracellular traps as mediators of thrombosis in COVID-19.

Abnormal coagulation and an increased risk of thrombosis are features of severe COVID-19, with parallels proposed with hemophagocytic lymphohistiocytosis (HLH), a life-threating condition associated with hyperinflammation. The presence of HLH was described in severely ill patients during the H1N1 influenza epidemic, presenting with pulmonary vascular thrombosis. We tested the hypothesis that genes causing primary HLH regulate pathways linking pulmonary thromboembolism to the presence of SARS-CoV-2 using novel network-informed computational algorithms. This approach led to the identification of Neutrophils Extracellular Traps (NETs) as plausible mediators of vascular thrombosis in severe COVID-19 in children and adults. Taken together, the network-informed analysis led us to propose the following model: the release of NETs in response to inflammatory signals acting in concert with SARS-CoV-2 damage the endothelium and direct platelet-activation promoting abnormal coagulation leading to serious complications of COVID-19. The underlying hypothesis is that genetic and/or environmental conditions that favor the release of NETs may predispose individuals to thrombotic complications of COVID-19 due to an increase risk of abnormal coagulation. This would be a common pathogenic mechanism in conditions including autoimmune/infectious diseases, hematologic and metabolic disorders.