scholarly journals The Compass-COVID19-ICU Study: Identification of Factors to Predict the Risk of Intubation and Mortality in Patients with Severe COVID-19

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2121-2121
Author(s):  
Patrick Van Dreden ◽  
Douglas D Fraser ◽  
Guillaume Voiriot ◽  
Aurélie Rousseau ◽  
Ismail Elalamy ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Research Funding ◽  
Cell Activation ◽  
Prognostic Score ◽  
Unmet Need ◽  
High Sensitivity ◽  
Protein S ◽  
Clinical Predictors ◽  
Endothelial Cell Activation ◽  
D Dimer

Abstract Background: In some patients, SARS-CoV-2 infection induces cytokine storm, hypercoagulability and endothelial cell activation leading to worsening of COVID-19, intubation and death. Prompt identification of patients at risk of intubation or death is un unmet need. Objective: To derive a prognostic score for the risk of intubation or death in patients with critical COVID-19 by assessing biomarkers of hypercoagulability, endothelial cell activation and inflammation and a large panel of clinical analytes. Methods: We conducted a prospective, observational monocentric study enrolling 118 patients with COVID-19 admitted in the intensive care unit. At the 1st day of ICU admission all patients were assessed for the following biomarkers : protein C, protein S, antithrombin, D-Dimer, fibrin monomers, factors VIIa, V, XII, XII, VIII, von Willebrand antigen, fibrinogen, procoagulant phospholipid dependent clotting time, TFPI, thrombomodulin, P-selectin, heparinase, microparticles exposing tissue factor, IL-6, complement C3a, C5a, thrombin generation, prothrombin time, activated partial thromboplastin time, hemogram, platelet count) and clinical predictors. The clinical outcomes were intubation and mortality during hospitalization in ICU. Results: The intubation and mortality rate were 70 % and 18% respectively. Multivariate analysis led to the derivation of the COMPASS- COVID19-ICU score composed of P-Selectin, D-Dimer, free TFPI, TF activity, IL-6 and FXII, age and duration of hospitalization. The score predicted the risk of intubation or death with high sensitivity and specificity (0.90 and 0.92, respectively). Conclusions and Relevance: Critical COVID-19 is related with severe endothelial cell activation and hypercoagulability orchestrated in the context of inflammation. The COMPASS-COVID19-ICU score is an accurate predictive model for the evaluation of the risk of mechanical ventilation and death in patients with critical COVID-19. The assessment with the COMPASS- COVID-19-ICU score is feasible in tertiary hospitals. In this context it could be placed in the diagnostic procedure of personalized medical management and prompt therapeutic intervention. Disclosures Terpos: Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding. Dimopoulos: Amgen: Honoraria; BMS: Honoraria; Takeda: Honoraria; Beigene: Honoraria; Janssen: Honoraria.

scholarly journals Prospective Assessment of Biomarkers of Hypercoagulability in Oncological Patients and Healthcare Workers Following Vaccination Against Sars-Cov-2 with the mRNA Vaccine. the Roadmap-COVID-19-Vaccin Study

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3207-3207
Author(s):  
Patrick Van Dreden ◽  
Joseph Gligorov ◽  
Evangelos Terpos ◽  
Mathieu Jamelot ◽  
Michele Sabbah ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Tissue Factor ◽  
Platelet Activation ◽  
Research Funding ◽  
Thrombin Generation ◽  
Cell Activation ◽  
Control Group ◽  
Clotting Time ◽  
Endothelial Cell Activation ◽  
Active Cancer

Abstract Background: COVID-19 has been associated with hypercoagulability, endothelial cell injury and frequent thrombotic complications resulting both from direct effects of the virus on the endothelium and from the 'cytokine storm' resulting from the host's immune response. Since the COVID-19 vaccines have been shown to effectively prevent symptomatic infection including hospital admissions and severe disease, the risk of COVID-19-related thrombosis should be expected to (almost) disappear in vaccinated individuals. However, some rare cases of venous thrombosis have been reported in individuals vaccinated with mRNA vaccines. Thus, there is a sharp contrast between the clinical or experimental data reported in the literature on COVID-19 and on the rare thrombotic events observed after the vaccination with these vaccines. This phenomenon raised some scepticism of even some fear about the safety of these vaccines which could compromise the adhesion of the citizens in the vaccination program. Aims: We conducted a prospective observational study, to explore the impact of vaccination with the BNT162b2 (Pfizer/BioNTech) on blood hypercoagulability and endothelial cell activation and to investigate if this is modified by the presence of active cancer. Methods: In total 229 subjects were prospectively included in the study from April to June 2021. Subjects were stratified in three predefined groups: 127 vaccinated patients with active cancer (VOnco group), 72 vaccinated health care workers (VHcw group) and 30 non vaccinated health individuals (Control group). Blood samples were obtained 2 days after the administration of the first dose of BNT162b2 vaccine and collected in Vacutainer® tubes (0.109 mol/L trisodium citrate). Platelet poor plasma (PPP) was prepared by double centrifugation at 2000 g for 20 minutes at room temperature and plasma aliquots were stored at -80°C until assayed. Samples of PPP were assessed for thrombin generation (TG) with PPP-Reagent® (Thrombogram-Thrombinoscope assay with PPP-Reagent®TF 5pM), E-selectin, D-dimers, (D-Di), Tissue Factor (TFa), procoagulant phospholipid-dependent clotting time (Procag-PPL) and von Willebrand factor (vWF), thrombomodulin (TM), tissue factor pathway inhibitor (TFPI), and platelet factor 4 (PF4). All assays were from Diagnostica Stago (France). The upper and lower normal limits (UNL and LNL) for each biomarker were calculated by the mean±2SD for the control group. Results: All vaccinated subjects showed significantly increased levels of PF4 (71% >UNL, p<0.001), D-Dimers (74% >UNL, p<0.01), vWF (60% >UNL, p<0.01), FVIII (62% >UNL, p<0.01) and shorter Procoag-PPL clotting time (96% <LNL, p<0.001), as compared to controls. Thrombin generation showed significantly higher Peak (60% >UNL, p<0.01), ETP (38% >UNL, p<0.01) and MRI (66% >UNL, p<0.01) but no differences in lag-time in vaccinated subjects as compared to the control group. Vaccinated subjects did not show any increase at the levels of TFa, TFPI, TM and E-selectin in comparison with the control group. The studied biomarkers were not significantly different between the VOnco and VHcw groups. Conclusion: The ROADMAP-COVID-19-Vaccine study shows that administration of the first dose of the BNT162b2 vaccine induced significant platelet activation documented by shorter Procoag-PPL associated with increased levels of PF4. Plasma hypercoagulability was less frequent in vaccinated individuals whereas there was no evidence of significant endothelial cells activation after vaccination. Interestingly, the presence of active cancer was not associated with an enhancement of platelet activation, hypercoagulability, or endothelial cell activation after the vaccination. Probably, the generated antibodies against the spike protein or lead to platelet activation in a FcyRIIa dependent manner that results in PF4 release. The implication of the mild inflammatory reaction triggered by the vaccination could be another possible pathway leading to platelet activation. Nevertheless, vaccination does not provoke endothelial activation even in patients with cancer. The findings of the ROADMAP-COVID-19-Vaccine study support the concept administration of mRNA based vaccines does not directly cause a systematic hypercoagulability. Disclosures Gligorov: Roche-Genentech: Research Funding; Novartis: Research Funding; Onxeo: Research Funding; Daichi: Research Funding; MSD: Research Funding; Eisai: Research Funding; Genomic Heatlh: Research Funding; Ipsen: Research Funding; Macrogenics: Research Funding; Pfizer: Research Funding. Terpos: Novartis: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding. Dimopoulos: Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria; Beigene: Honoraria; Takeda: Honoraria.

Age-Related Reference Values of Molecular Markers in Endothelial Cell Activation, Coagulation and Fibrinolysis in Thai Children Versus Adults.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4040-4040
Author(s):  
Darintr Sosothikul ◽  
Jeanne M. Lusher
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Reference Values ◽  
Cell Activation ◽  
Age Groups ◽  
Factor Vii ◽  
Endothelial Cell Activation ◽  
Hemostatic System ◽  
Pai 1 ◽  
D Dimer

Abstract Introduction: The hemostatic system is a developing and changing process relative to age. Although advances in the knowledge of hemostatic mechanisms have led to the development of new methods for measuring peptides or enzyme-inhibitor complexes, there are very limited data concerning normal reference values for these in children. Objectives: The aim of this study is to distinguish the difference(s) in various endothelial cell activation and hemostatic parameters between children and adults, and to establish the normal range of these parameters in normal children in different age groups. Materials and Methods: Blood was obtained from 96 normal Thai children and adults whose screening coagulation tests were normal. All children were categorized into 3 age groups: 1–5 yrs, 6–10 yrs, and 11–18 yrs. Endothelial cell activation parameters: von Willebrand Factor Antigen and Activity (VWF:Ag and VWF:Ac) and soluble thrombomodulin (sTM); coagulation parameters: activated Factor VII (FVIIa:C), tissue factor (TF), and Thrombin-Antithrombin Complex (TAT); and fibrinolytic parameters: tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1), D-dimer, thrombin activatable fibrinolysis inhibitor (TAFIa) and Protein C activity (PC:Ac) were measured. Tests Children’s Age Range Adults (Mean ± SD) 1–5 yr (n=19) 6–10 yr (n=26) 11–18 yr (n=25) (n=25) ANOVA *p ≤ 0.05 compared with adults; **p ≤ 0.001 compared with adults VWF:Ag (%) 93.3 ± 25.7 110.3 ± 27.1 98.4 ± 31.0 100.5 ± 25.2 VWF:Ac (%) 72.1 ± 18.9 91.1 ± 20.6 82.0 ± 24.2 84.7 ± 21.8 sTM (ng/mL) 3.9 ± 1.6** 3.1 ± 0.9 3.1 ± 1.3 2.4 ± 1.1 Fibrinogen (mg/dL) 360.7 ± 56.9 384.4 ± 78.9 410.1 ± 109.4 360.7 ± 51.0 FVIIa:C (%) 68.0 ± 23.8 69.9 ± 23.1 75.0 ± 22.9 75.6 ± 19.7 TF (pg/mL) 218.8 ± 57.8** 152.7 ± 38.2 144.5 ± 46.7 126.6 ± 42.2 TAT (ug/L) 4.5 ± 3.3 2.2 ± 0.7 2.4 ± 1.2 3.7 ± 4.9 t-PA (ng/mL) 1.32 ± 0.56 1.19 ± 0.48 1.16 ± 0.28 1.27 ± 0.32 PAI-1 (ng/mL) 22.8 ± 13.2 29.4 ± 14.2* 27.3 ± 18.3 18.8 ± 11.9 D-dimer (mg/L) 0.52 ± 0.42* 0.44 ± 0.46 0.28 ± 0.33 0.21 ± 0.09 TAFIa μg/mL) ( 40.6 ± 9.7 44.4 ± 6.9 46.1 ± 6.1 42.2 ± 5.7 Protein C:Ac (%) 87.2 ± 18.3* 101.7 ± 15.6 101.1 ± 22.5 102.4 ± 17.4 As seen in the Table, children in all age groups showed no significant difference in mean levels of VWF:Ag and Ac, fibrinogen, FVIIa:C, TAT, t-PA and TAFIa compared to adults. However, compared to adults, children aged 1–5 had significantly higher mean values of sTM (p=0.001), TF (p=< 0.001), and D-dimer (p = 0.015) whereas they had significantly lower mean levels of PC:Ac (p=0.023). The mean levels of PAI-1 in children of all groups were high, especially in children in the 6–10 yr age group (p = 0.032). These data indicate a physiologic difference in endothelial cell activation and hemostatic system between children and adults. Our data will serve as a useful reference guide in interpreting test results from children with suspected bleeding disorders.

scholarly journals Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria

2020 ◽  
Vol 14 (7) ◽  
pp. e0007656
Author(s):  
João Conrado Khouri Dos-Santos ◽  
João Luiz Silva-Filho ◽  
Carla C. Judice ◽  
Ana Carolina Andrade Vitor Kayano ◽  
Júlio Aliberti ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Plasmodium Vivax Malaria

scholarly journals Signs of sympathetic and endothelial cell activation in the skin of patients with restless legs syndrome

2021 ◽  
Author(s):  
Melanie Bergmann ◽  
Anna Heidbreder ◽  
Ambra Stefani ◽  
Cecilia Raccagni ◽  
Elisabeth Brandauer ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Restless Legs Syndrome ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Restless Legs

OR17 Heme oxygenase-1 modulates HLA class I antibody-dependent endothelial cell activation

2015 ◽  
Vol 76 ◽  
pp. 15
Author(s):  
Eva Zilian ◽  
Hendry Saragih ◽  
Oliver Hiller ◽  
Abid Aljabri ◽  
Constanca Figueiredo ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Heme Oxygenase ◽  
Cell Activation ◽  
Hla Class I ◽  
Class I ◽  
Heme Oxygenase 1 ◽  
Endothelial Cell Activation

scholarly journals Dengue Virus Induces the Expression and Release of Endocan from Endothelial Cells by an NS1–TLR4-Dependent Mechanism

2021 ◽  
Vol 9 (6) ◽  
pp. 1305
Author(s):  
Carlos Alonso Domínguez-Alemán ◽  
Luis Alberto Sánchez-Vargas ◽  
Karina Guadalupe Hernández-Flores ◽  
Andrea Isabel Torres-Zugaide ◽  
Arturo Reyes-Sandoval ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Mrna Expression ◽  
Cell Lines ◽  
Cell Activation ◽  
Dengue Infection ◽  
Elevated Serum ◽  
Fold Increase ◽  
Endothelial Cell Activation ◽  
Stimulation Of

A common hallmark of dengue infections is the dysfunction of the vascular endothelium induced by different biological mechanisms. In this paper, we studied the role of recombinant NS1 proteins representing the four dengue serotypes, and their role in promoting the expression and release of endocan, which is a highly specific biomarker of endothelial cell activation. We evaluated mRNA expression and the levels of endocan protein in vitro following the stimulation of HUVEC and HMEC-1 cell lines with recombinant NS1 proteins. NS1 proteins increase endocan mRNA expression 48 h post-activation in both endothelial cell lines. Endocan mRNA expression levels were higher in HUVEC and HMEC-1 cells stimulated with NS1 proteins than in non-stimulated cells (p < 0.05). A two-fold to three-fold increase in endocan protein release was observed after the stimulation of HUVECs or HMEC-1 cells with NS1 proteins compared with that in non-stimulated cells (p < 0.05). The blockade of Toll-like receptor 4 (TLR-4) signaling on HMEC-1 cells with an antagonistic antibody prevented NS1-dependent endocan production. Dengue-infected patients showed elevated serum endocan levels (≥30 ng/mL) during early dengue infection. High endocan serum levels were associated with laboratory abnormalities, such as lymphopenia and thrombocytopenia, and are associated with the presence of NS1 in the serum.

scholarly journals Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways

Blood ◽  
1990 ◽  
Vol 76 (12) ◽  
pp. 2520-2526 ◽  
Author(s):  
SJ van Deventer ◽  
HR Buller ◽  
JW ten Cate ◽  
LA Aarden ◽  
CE Hack ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Plasminogen Activator ◽  
Cell Activation ◽  
Plasminogen Activator Inhibitor ◽  
Contact System ◽  
Initial Increase ◽  
Cytokine Release ◽  
Endothelial Cell Activation ◽  
System A ◽  
Von Willebrand

Abstract Endotoxemia was evoked by bolus injection of Escherichia coli endotoxin (2 ng/kg body weight) in six healthy subjects to investigate the early kinetics of cytokine release in relation to the development of clinical and hematologic abnormalities frequently seen in gram-negative septicemia. The plasma concentration of tumor necrosis factor (TNF) increased markedly after 30 to 45 minutes, and reached a maximal level after 60 to 90 minutes. In each volunteer, the initial increase of plasma interleukin 6 (IL-6) concentrations occurred 15 minutes after the initial TNF increase, and maximal IL-6 concentrations were reached at 120 to 150 minutes. A transient increase in body temperature and pulse rate occurred simultaneously with the initial TNF and IL-6 increases, whereas a significant decrease in blood pressure occurred after 120 minutes. These changes were proportional to the changes in TNF and IL-6 concentrations. Coagulation activation, as assessed by a rise of prothrombin fragments and thrombin-antithrombin III complexes, was noted after 120 minutes, in the absence of activation of the contact system. A two- to sixfold increase in the concentrations of tissue plasminogen activator (t-PA) and von Willebrand factor antigen indicated endothelial cell activation. This increase started at 120 and 90 minutes, respectively. The release of t-PA coincided with activation of the fibrinolytic pathway, as measured by plasmin-alpha 2-antiplasmin complexes. The fibrinolytic activity of t-PA was subsequently offset by release of plasminogen activator inhibitor, observed 150 minutes after the endotoxin injection, and reaching a peak at 240 minutes. No complement activation was detected. These results show that in humans endotoxin induces an early, rapidly counteracted fibrinolytic response, and a more long-lasting activation of thrombin by a mechanism other than contact system activation. In addition, our data suggest that endotoxin-induced leukopenia and endothelial cell activation are mediated by TNF.

Sign in / Sign up

Export Citation Format

Share Document