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.

Factor Vila and other Haemostatic Variables following Bone Marrow Transplantation

1994 ◽  
Vol 72 (01) ◽  
pp. 028-032 ◽  
Author(s):  
P Collins ◽  
A Roderick ◽  
D O’Brien ◽  
E Tuddenham ◽  
A O’Driscoll ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Endothelial Cell ◽  
Bone Marrow Transplantation ◽  
Tissue Factor ◽  
Marrow Transplantation ◽  
General Circulation ◽  
Cell Activation ◽  
Convincing Evidence ◽  
Endothelial Cell Activation

SummaryHepatic venocclusive disease causes considerable morbidity and mortality following bone marrow transplantation. There are two hypotheses regarding the aetiology of this syndrome; firstly that changes in plasma coagulation factors and natural anticoagulants lead to a prothrombotic state and secondly that endothelial cell activation stimulates intravascular deposition of fibrin. We have investigated these mechanisms by measuring the changes in proteins C and S and factors VII and X in the post transplant period and by using the plasma concentration of factor Vila as an in vivo marker of potential endothelial cell tissue factor expression. Protein C fell in both allograft and autograft patients but more so in the allografts. Similar results were found for factors VII and X. These changes were predominantly due to hepatic dysfunction induced by the chemo-radiotherapy. Factor Vila levels were unchanged in both the allograft and autograft patients. We conclude that there is no convincing evidence for a procoagulant state following BMT as there are both anticoagulant and procoagulant changes. The absence of any changes in factor Vila levels suggests that tissue factor was not exposed to the general circulation following BMT but does not exclude focal expression at the sites of thrombosis.

Profile of Thrombin Generation Assay and Thromboelastometry in Women with Moderate and Severe Preeclampsia. the Roadmap-Preeclampsia Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 37-38
Author(s):  
Patrick Van Dreden ◽  
Elmina Lefkou ◽  
Aurélie Rousseau ◽  
Grigorios T. Gerotziafas
Keyword(s):  
Endothelial Cell ◽  
Thrombin Generation ◽  
Cell Activation ◽  
Lag Time ◽  
Clot Formation ◽  
Endothelial Cell Activation ◽  
Thrombin Generation Assay ◽  
Formation Kinetics ◽  
The Mean ◽  
Α Angle

Introduction: Preeclampsia is a frequent vascular complication of pregnancy and figures among the major causes of maternal and neonatal morbidity and mortality. Early diagnosis and prompt, targeted treatment remain a unmet need. Hypercoagulability and endothelial cell activation are among the principal pathogenetic mechanisms in patients with preeclempsia. Development of diagnostic algorithms including clinically relevant biomarkers of hypercoagulability is expect to improve the management of preeclampsia. Among the numerous coagulation test, Global Coagulation Assays (GCA) such as thrombogram and thromboelastometry, could be of potential value for the evaluation of blood hypercoagulability. They provide information, on thrombin generation process, clot formation kinetics, clot firmness and even fibrinolysis potential. Aim: In this study we investigated the clinical accuracy of whole blood thromboelastometry (ROTEM®), and thrombin generation assay (calibrated automated thrombography: CAT® assay) to identify women with preeclampsia and we tried to compare their sensitivity. Methods: An observational retrospective case-control study was conducted. Plasma samples were collected from 84 women divided into three groups, the healthy pregnant (HP) group (n=35), the mild preeclampsia (MP) group (n=34) and the severe preeclampsia (SP) group (n=15). Thromboelastometry in whole blood was performed on ROTEM delta instrument (Tem Innovations GmbH, Werfen, Munich, Germany) with INTEM reagent. Thrombin generation triggered by PPP reagent low® (1 pM TF and 4µM phospholipid) was measured in platelet poor plasma. Thrombogram was also assessed in the presence or absence of thrombomodulin and the corresponding ration was calculated. Blood was collected at the diagnosis of preeclampsia (groups MP and SP) or at the equivalent months of pregnancy in the control group (HP). Statistical analysis was performed using the PASW Statistics 17.0.2 (SPSS Inc.) for Windows. Results: Thromboelastometry analysis showed that the clotting time (CT) was significantly longer in SP group as compared to MP and HP group. Both preeclampsia groups had longer clot formation time (CFT as compared to HP-group. MP-group had longer CFT as compared to SP-group. The α angle was significantly lower in SP-group as compared to the HP and MP groups. The maximum clot firmness was significantly higher in MP groups as compared to either HP or SP-group. The mean lysis (ML) was lower in both preeclampsia groups as compared to the HP group (Table 1). Thrombogram analysis showed that the lag-time of thrombin generation was significantly longer in both MP and SP groups as compared to HP group. Moreover, SP group showed significantly longer lag -time as compared to MP-group. Peak and the endogenous thrombin potential (ETP) were significantly higher in MP group as compared to either HP or SP groups. The mean rate index of the propagation phase of thrombin generation was not significantly different among the three groups whereas the thrombomodulin ratio for the ETP was significantly shorter in the SP-group (Table 2). Both tests showed a significant prolongation of the initiation phase of blood coagulation (reflected on CT and lag-time) in SP. The levels of clotting factors and fibrinogen were normal in all patients and none was on anticoagulant treatment. Thus, this prolongation reflects changes at the levels of TFPI and Thrmbomodulin reflecting an endothelial cell activation. ROTEM showed a decrease of the α-angle and MCF in SP group which is related with a lower platelet count in these patients. ROTEM showed enhanced fibrinolysis in both MP and SP groups Women with MP showed higher Peak and ETP than SP, MP showed higher ratio of ETP (TM+/TM-) than SP. Conclusion: The two GCA proved complementary information on the status of blood coagulation in pregnant women with preeclampsia. ROTEM provides information on clot formation kinetics and clot firmness as well as on fibrinolysis activation, which allow to differentiate SP from HP. However, the capacity of the assay for identification of patients with MP is limited. Thrombin generation assay showed a distinct profile between the three groups, which allowed differentiating the MP from HP as well as from SP. Disclosures No relevant conflicts of interest to declare.

scholarly journals Laser-induced endothelial cell activation supports fibrin formation

Blood ◽  
2010 ◽  
Vol 116 (22) ◽  
pp. 4675-4683 ◽  
Author(s):  
Ben T. Atkinson ◽  
Reema Jasuja ◽  
Vivien M. Chen ◽  
Prathima Nandivada ◽  
Bruce Furie ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Tissue Factor ◽  
Cell Activation ◽  
Umbilical Vein ◽  
Calcium Mobilization ◽  
Endothelial Cell Activation ◽  
Human Umbilical Vein ◽  
Laser Injury ◽  
Umbilical Vein Endothelial Cells

Laser-induced vessel wall injury leads to rapid thrombus formation in an animal thrombosis model. The target of laser injury is the endothelium. We monitored calcium mobilization to assess activation of the laser-targeted cells. Infusion of Fluo-4 AM, a calcium-sensitive fluorochrome, into the mouse circulation resulted in dye uptake in the endothelium and circulating hematopoietic cells. Laser injury in mice treated with eptifibatide to inhibit platelet accumulation resulted in rapid calcium mobilization within the endothelium. Calcium mobilization correlated with the secretion of lysosomal-associated membrane protein 1, a marker of endothelium activation. In the absence of eptifibatide, endothelium activation preceded platelet accumu-lation. Laser activation of human umbilical vein endothelial cells loaded with Fluo-4 resulted in a rapid increase in calcium mobilization associated cell fluorescence similar to that induced by adenosine diphosphate (10μM) or thrombin (1 U/mL). Laser activation of human umbilical vein endothelial cells in the presence of corn trypsin inhibitor treated human plasma devoid of platelets and cell microparticles led to fibrin for-mation that was inhibited by an inhibitory monoclonal anti–tissue factor antibody. Thus laser injury leads to rapid endothelial cell activation. The laser activated endothelial cells can support formation of tenase and prothrombinase and may be a source of activated tissue factor as well.

scholarly journals Extracellular Vesicles Derived from HT-29 Colorectal Cancer Cells Induce Endothelial Cell Activation and Procoagulant Activity

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3456-3456
Author(s):  
Yun Tian ◽  
Meifang Wu ◽  
Alok A. Khorana ◽  
Keith R. McCrae
Keyword(s):  
Colorectal Cancer ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Board Of Directors ◽  
Tissue Factor ◽  
Cell Activation ◽  
Endothelial Cell Activation ◽  
Advisory Committees ◽  
Cell Monolayers ◽  
Ht 29

Abstract Introduction: Hypercoagulability leading to thromboembolic complications is associated with significant morbidity and mortality in patients with colorectal cancer, however the underlying mechanisms are not well understood. Elevated levels of extracellular vesicles (EV), both microparticles (> 100 nm) and exosomes (< 100 nm), circulate in patients with colorectal cancer. While some studies suggest that EV-expressed tissue factor is associated with thrombosis in patients with cancer, overall results are inconsistent. However, EV contain many other mediators such as inflammatory cytokines and microRNAs (miRNA) that may be transferred to other cells and induce phenotypic changes. We hypothesized that EV derived from colorectal cancer cells in vitro would induce endothelial cell activation and promote endothelial cell procoagulant activity. Methods: Human colorectal adenocarcinoma cells (HT-29) were cultured at a density of 1.0×107 cells per T75 flask in EV-free media containing 2% FBS, and after removal of floating cells and cell debris, microparticles were collected by centrifugation at 20,000 x G for 15 minutes; each flask contained approximately 4.0 x 106 annexin V+ microparticles. Exosomes were collected by additional centrifugation of the supernatant at 100,000 x G for 90 minutes. Microparticles and exosomes, at different dilutions, were separately co-cultured with confluent endothelial cell monolayers in 6 or 96-well plates, for 6 hours, using TNF-α (4 ng/ml) as a positive control. Endothelial cell activation was assessed by measuring expression of E-selectin, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), Il-1β and tissue factor by quantitative RT-PCR (qPCR) and immunoblotting. We also analyzed the effects of microparticles and exosomes on endothelial cell procoagulant activity by layering plasma over confluent endothelial cell monolayers. Briefly, after incubating endothelial cell monolayers with microparticles or exosomes (or 4 ng/ml TNFα as a positive control) for 6 hours, monolayers were washed three times with 20mM HEPES buffer (pH 7.4) containing 5mM calcium chloride and then overlaid with 100 µl per well of pooled normal human plasma. Plasma was re-calcified by the addition of 11 ul 200 mM calcium chloride, and plates were then placed in a kinetic microtiter-plate reader (Synergy HT) maintained at 37°C, and fibrin formation measured as an increase in the optical density at 405 nm. Results: Microparticles and exosomes constitutively released by HT-29 cells induced activation of endothelial cells in a concentration-dependent manner. Significant increases in the expression of E-selectin, ICAM-1, VCAM-1, tissue factor and IL-1β mRNA and protein were observed (Figure 1). In general, microparticles were more potent in inducing endothelial cell activation than exosomes when the EV were derived from the same number of HT-29 cells, though quantification of small exosomes is imprecise. Interestingly, while the response of endothelial cells to microparticles and exosomes was generally similar to that of 4 ng/ml TNFα, both types of EV appeared more potent in the induction of endothelial cell tissue factor, particularly at the mRNA level. HT-29 cell-derived EV, both microparticles and exosomes, also significantly shortened the clotting time of recalcified plasma added to endothelial cell monolayers (Figure 2). Conclusions: EV constitutively released from HT-29 cells, both microparticles and exosomes, directly activate cultured endothelial cells leading to increased expression of cell adhesion molecules, elaboration of IL-1β, and expression of tissue factor. The change in endothelial phenotype is not due to simple transfer of biomolecules since EV stimulated changes at the mRNA and protein level. While responses to microparticles and exosomes were similar, some differences were observed, suggesting that different underlying mechanisms may contribute. Endothelial cell activation in response to EV leads to accelerated clotting of plasma on the endothelial cell monolayer. These findings suggest a novel effect of cancer cell-derived EV that may contribute to the hypercoagulability present in patients with malignancy. Disclosures Khorana: Daiichi Sankyo: Consultancy, Honoraria; Boehringer-Ingelheim: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; sanofi: Consultancy, Honoraria. McCrae:Momenta: Consultancy; Halozyme: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Syntimmune: Consultancy.

Platelet degranulation and glycoprotein IIbIIIa opening are not related to bleeding phenotype in severe haemophilia A patients

2014 ◽  
Vol 111 (06) ◽  
pp. 1022-1030 ◽  
Author(s):  
Roger E. G. Schutgens ◽  
Kathelijn Fischer ◽  
Philip G. de Groot ◽  
Mark Roest ◽  
Esther R. van Bladel
Keyword(s):  
Endothelial Cell ◽  
Platelet Activation ◽  
Cell Activation ◽  
Clinical Phenotype ◽  
Platelet Reactivity ◽  
Joint Damage ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Endothelial Cell Activation ◽  
Bleeding Score

SummaryRecently we reported data suggesting that platelets could compensate for the bleeding phenotype in severe haemophilia A (HA). The aim of this study was to confirm these results in a larger population with a detailed characterisation of clinical phenotype. Patients with diagnostic severe HA (FVIII:C <1%) were scored for clinical phenotype by integrating data on age at first joint bleed, joint damage, bleeding frequency and FVIII consumption. Phenotype was defined as onset of joint bleeding-score + arthropathy-score + joint bleeding-score + (2* treatment intensity-score). After a washout period of three days, blood was collected for measurement of basal level of platelet activation, platelet reactivity, endothelial cell activation and presence of procoagulant phospholipids in plasma. Thirty-three patients with severe HA were included, 13 patients with a mild, 12 patients with an average and eight patients with a severe clinical phenotype. No relevant differences in basal level of platelet activation, platelet reactivity, endothelial cell activation and procoagulant phospholipids between all three groups were observed. The mean annual FVIII consumption per kg did not correlate with the platelet P-selectin expression and glycoprotein (GP)IIbIIIa activation on platelets. In conclusion, variability in clinical phenotype in patients with diagnostic severe HA is not related to platelet activation or reactivity, measured as platelet degranulation and platelet GPIIbIIIa opening.

Polyethylene Glycol Modification of Adenovirus Reduces Platelet Activation, Endothelial Cell Activation, and Thrombocytopenia

2007 ◽  
Vol 18 (9) ◽  
pp. 837-848 ◽  
Author(s):  
Sean E. Hofherr ◽  
Hoyin Mok ◽  
Francisca C. Gushiken ◽  
Jose A. Lopez ◽  
Michael A. Barry
Keyword(s):  
Polyethylene Glycol ◽  
Endothelial Cell ◽  
Platelet Activation ◽  
Cell Activation ◽  
Endothelial Cell Activation

scholarly journals Biomarkers of Hypercoagulability and Endothelial Cell Activation in Patients with Severe COVID-19 Admitted at the Intensive Care Unit. the Roadmap-COVID-19 Prospective Observational Study

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Patrick Van Dreden ◽  
Guillaume Voiriot ◽  
Alexandre Alabbadi ◽  
Ismail Elalamy ◽  
Loula Papageorgiou ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Thrombin Generation ◽  
Cell Activation ◽  
Moderate Increase ◽  
Healthy Individuals ◽  
Coagulation Activation ◽  
Endothelial Cell Activation ◽  
High Increase ◽  
Cellular Origin ◽  
Screening Algorithm

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) characterized by acute pneumonia which may progress to respiratory failure and life-threatening complications, including acute respiratory distress syndrome (ARDS) and multisystem organ failure with fatal outcome. COVID-19 should be regarded as a systemic disease involving multiple systems. COVID-19 is associated with excessive inflammation, platelet activation, endothelial dysfunction, blood coagulation activation and fibrin formation. The development of a screening algorithm for the evaluation of endothelial and blood coagulation activation is an urgent need for the optimisation of the management of the patients with severe COVID-19. To this aim biomarkers of endothelial cell activation and hypercoagulability have central place Aim: The prospective observational monocentric cohort study ROADMAP-COVID-19 study aimed to evaluate the biomarkers of hypercoagulability and endothelial cell activation which they could be used in the development of a screening algorithm in patients with COVID-19 Methods: The ROADMAP-COVID-19 study enrolled 90 consecutive patients hospitalized at Tenon University Hospital (AP-HP, Paris) between March 18th and April 30th, 2020 with confirmed SARS-CoV-2 infection admitted to the ICU with clinically deteriorated severe COVID-19 (ICU- group). Patients were assessed upon the first day to the ICU admission. The control group consisted 30 healthy individuals (C-group). All patients and controls were evaluated for, clotting times (PT and aPTT), fibrinogen, D-Dimers, antithrombin (AT), protein C (PC) and protein S (Ps) activity, clotting factors V (FV), VIII (FVIII) and XII (FXII), high molecular weight kininogen (HK), von Willebrand factor (FvW), thrombin generation assay (TG) using TF 20 pM-PPP-Reagent® (Thrombogram-Thrombinoscope from Stago), fibrin monomers (FM), free TFPI and TF activity, thrombomodulin activity (TM), TF expressing microparticles (the ratio TF/TFPI was also calculated) and Heparanase. The IL-6 levels were also measured. All patients hospitalized in conventional medical department or in ICU routinely received thromboprophylaxis with body weight adapted enoxaparin. The ratio of the mean values of each studied biomarker in the ICU and the C-group was calculated. Biomarkers were classified in four clusters (Decrease, Stable, Slight Increase, Moderate Increase and High Increase). Results :The ICU-group consisted of 102 patients; 87% of these patients were admitted to the ICU directly from the emergency department. Males were 76 out of 102 patients. Age ranged from 30 to 93 years in the W-group. The changes of the biomarkers in patients with COVID-19 admitted at the ICU as compared to healthy individuals with are shown in Table 1. The ICU patients with COVID-19 were characterized by marked increase of IL-6 followed by increase of heparanase and D-dimers. The PPL-ct showed the most important decrease. Patients showed a significant decrease in FXII levels which was associated with a moderate increase of kininogen levels. The levels of the natural coagulation inhibitors as well as the clotting times (PT and aPTT) did not significantly modify in patients as compared to the controls. The rate of the propagation phase of thrombin generation (MRI) and the Peak of thrombin were significantly decrease and the lag-time was prolonged reflecting the antithrombotic effect of treatment with LMWH. Heparanse, free TFPI, and TM showed moderate or high increase. The decreased Ratio of TF/TFPI indicated that the free TFPI release dominated over the release of soluble TF activity. Conclusion: Patients with severe COVID-19 requiring ICU admission showed inhaled inflammatory reaction, hyperocoagulability and endothelial cell activation whereas platelet activation appeared to be secondary. Among the studied biomarkers the PPL-ct D-dimers and heparanase followed by TFPI, FvW, FM and TM levels appear to be mandatory for hypercoagulability of cellular origin. Interestingly patients with severe COVID-19 showed consumption of FXII indicating intrinsic clotting pathway activation and high levels of HK which also indicates endothelial cell activation. The clinical relevance of these biomarkers for early detection of hypercoagulability of cellular origin in patients with COVID-19 is being evaluated in prospective study. Disclosures No relevant conflicts of interest to declare.

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.

The Origin of P-selectin as a Circulating Plasma Protein

1997 ◽  
Vol 77 (06) ◽  
pp. 1081-1085 ◽  
Author(s):  
R Fijnheer ◽  
C J M Frijns ◽  
J Korteweg ◽  
H Rommes ◽  
J H Peters ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Platelet Count ◽  
Endothelial Cell ◽  
Cell Activation ◽  
Control Group ◽  
Healthy Controls ◽  
Healthy Individuals ◽  
Endothelial Cell Activation ◽  
Bone Marrow Aplasia ◽  
Thrombocytopenic Purpura

SummaryP-selectin is a 140 kD protein found in the α-granules of platelets and the Weibel-Palade bodies of endothelial cells. On cell activation it is expressed on the cell surface and also secreted into plasma. Whether the circulating soluble P-selectin (sP-selectin) originates from platelets, endothelial cells, or both, is not known. We studied the level of sP-selectin in diseases with different platelet counts, with or without evidence of endothelial cell activation. Endothelial cell activation was confirmed by the detection of sE-selectin and EDl-fibronectin. A significant positive correlation between platelet count and sP-selectin concentration was observed in healthy controls, and in patients with thrombocytopenia due to bone marrow aplasia, or with thrombocytosis (r = 0.85; n = 47; p <0.001). In patients with idiopathic thrombocytopenic purpura (ITP) the sP-selectin concentration was 110 ± 39 ng/ml (n = 10), compared to 122 ± 38 ng/ml in healthy controls (n = 26). However, their mean platelet count was lower (58 X 109/1 versus 241 X 109/1 in the control group). Accordingly, the levels of sP-selectin expressed per platelet increased to significantly higher levels (2.0 ± 1.2 versus 0.6 ± 0.2 fg/platelet in the control group-; p <0.0001). This suggests increased platelet turnover in patients with ITP. High levels of sP-selectin were found in patients with sepsis (398 ± 203 ng/ml; n = 15) and with thrombotic thrombocytopenic purpura (TTP; 436 ± 162 ng/ml; n = 12). Compared with patients with ITP, the concentration of sP-selectin per platelet was higher in patients with sepsis (4.8 ± 4.3 fg/platelet; p <0.005) or TTP (17.1 ± 9.5 fg/platelet; p <0.001). Endothelial cells are very likely to be the source in these patients and the presence of endothelial cell activation was confirmed by increased levels of circulating E-selectin and ED 1 -fibronectin.This study suggests that platelets are the major source of circulating sP-selectin in healthy individuals. Endothelial cell activation is associated with an increased sP-selectin concentration per platelet.

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