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human thrombomodulin duoset elisa  (R&D Systems)


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    R&D Systems human thrombomodulin duoset elisa
    Assessments of mechanisms leading to increased sTM levels following stimulation with S. aureus proteins. HUVEC monolayers were stimulated for 22 h with supernatant of overnight cultures of clinically isolated strains of S. aureus (M37, P08) and α-toxin. sTM was assessed in the host cell culture supernatant of stimulated cells (A). <t>Thrombomodulin</t> gene (THBD) expression in HUVECs after stimulation was assessed by qPCR (B) and total TM levels were measured after cell lysis of stimulated cells (C). LDH and TM were measured in cell culture supernatants after stimulations, with and without addition of 1300 nM broad-spectrum MMP inhibitor Marimastat (MMPI) or 10,6 µM ADAM10 selective inhibitor GI254023X (A10I) (D-E). LDH release measurements indicate cytotoxicity. Quantification of sTM and LDH are given in corrected optical density values. Asterisks indicate statistically significant differences (* = p < 0.05, ** = p < 0.01, *** = p < 0.001) according to ANOVA followed by Fisher’s least significant difference (LSD) post hoc test (A, B, C) or student t-test (D, E). Colors indicate different stimuli and symbols indicate different biological replicates. Direct cleavage of 40 ng rTM by 100 ng rADAM10 (rA10) was evaluated by western blot after 2 h incubation at 37 °C, with or without MMPI or A10I (F). Cleavage products are indicated by arrows at approximately 60 and 40 kDa.
    Human Thrombomodulin Duoset Elisa, supplied by R&D Systems, used in various techniques. Bioz Stars score: 93/100, based on 10 PubMed citations. ZERO BIAS - scores, article reviews, protocol conditions and more
    https://www.bioz.com/product/dy3947/Human+Thrombomodulin%2FBDCA-3+DuoSet+ELISA/pmc12721087-80-1-5
    Average 93 stars, based on 10 article reviews
    human thrombomodulin duoset elisa - by Bioz Stars, 2026-09
    93/100 stars

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    1) Product Images from "Staphylococcus aureus toxins mediate endothelial Thrombomodulin release during severe invasive infections"

    Article Title: Staphylococcus aureus toxins mediate endothelial Thrombomodulin release during severe invasive infections

    Journal: Virulence

    doi: 10.1080/21505594.2025.2605767

    Assessments of mechanisms leading to increased sTM levels following stimulation with S. aureus proteins. HUVEC monolayers were stimulated for 22 h with supernatant of overnight cultures of clinically isolated strains of S. aureus (M37, P08) and α-toxin. sTM was assessed in the host cell culture supernatant of stimulated cells (A). Thrombomodulin gene (THBD) expression in HUVECs after stimulation was assessed by qPCR (B) and total TM levels were measured after cell lysis of stimulated cells (C). LDH and TM were measured in cell culture supernatants after stimulations, with and without addition of 1300 nM broad-spectrum MMP inhibitor Marimastat (MMPI) or 10,6 µM ADAM10 selective inhibitor GI254023X (A10I) (D-E). LDH release measurements indicate cytotoxicity. Quantification of sTM and LDH are given in corrected optical density values. Asterisks indicate statistically significant differences (* = p < 0.05, ** = p < 0.01, *** = p < 0.001) according to ANOVA followed by Fisher’s least significant difference (LSD) post hoc test (A, B, C) or student t-test (D, E). Colors indicate different stimuli and symbols indicate different biological replicates. Direct cleavage of 40 ng rTM by 100 ng rADAM10 (rA10) was evaluated by western blot after 2 h incubation at 37 °C, with or without MMPI or A10I (F). Cleavage products are indicated by arrows at approximately 60 and 40 kDa.
    Figure Legend Snippet: Assessments of mechanisms leading to increased sTM levels following stimulation with S. aureus proteins. HUVEC monolayers were stimulated for 22 h with supernatant of overnight cultures of clinically isolated strains of S. aureus (M37, P08) and α-toxin. sTM was assessed in the host cell culture supernatant of stimulated cells (A). Thrombomodulin gene (THBD) expression in HUVECs after stimulation was assessed by qPCR (B) and total TM levels were measured after cell lysis of stimulated cells (C). LDH and TM were measured in cell culture supernatants after stimulations, with and without addition of 1300 nM broad-spectrum MMP inhibitor Marimastat (MMPI) or 10,6 µM ADAM10 selective inhibitor GI254023X (A10I) (D-E). LDH release measurements indicate cytotoxicity. Quantification of sTM and LDH are given in corrected optical density values. Asterisks indicate statistically significant differences (* = p < 0.05, ** = p < 0.01, *** = p < 0.001) according to ANOVA followed by Fisher’s least significant difference (LSD) post hoc test (A, B, C) or student t-test (D, E). Colors indicate different stimuli and symbols indicate different biological replicates. Direct cleavage of 40 ng rTM by 100 ng rADAM10 (rA10) was evaluated by western blot after 2 h incubation at 37 °C, with or without MMPI or A10I (F). Cleavage products are indicated by arrows at approximately 60 and 40 kDa.

    Techniques Used: Isolation, Cell Culture, Expressing, Lysis, Western Blot, Incubation

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    Concentration Assay:

    Article Title: Biomarkers for Predicting Malignant Pleural Mesothelioma in a Mexican Population
    Article Snippet: For mesothelin determination, sandwich ELISAs were performed according to the manufacturer ́s instructions (DY3265, R&D Systems, Minneapolis, MN). .. Thrombomodulin concentration was determined according to the manufacturer ́s instructions (DY3947, R&D Systems). ..

    Clinical Proteomics:

    Article Title: Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children
    Article Snippet: 33 Samples were immediately frozen at −80 ° C. Coagulation tests were determined on an MDA180 analyzer (Stago, France) and activated protein C (aPC) levels by enzyme-capture. .. 33 Plasma and CSF antigens were determined using commercial enzyme-linked immunosorbent assay kits: intracellular adhesion molecule-1 (ICAM-1, DY720; R&D), TM (DY3947; R&D), EPCR (0264; Stago, France), albumin (E80-129; Bethyl Laboratories), F1+2 (Enzygnost F1+2; Dade Behring, Germany), and TATs (Enzygnost TAT micro; Dade Behring). table ft1 table-wrap mode="anchored" t5 caption a7 Healthy controls Mild febrile illness Uncomplicated malaria Febrile controls (CSF samples) Nonmalarial coma Retinopathy-negative CM Retinopathy-positive CM (n = 30) (n = 32) (n = 31) (n = 14) (n = 16) (n = 41) (n = 161) Age, median years (IQR) 4.8 (2.7-8) 3.1 (1.8-5.4)* 5.4 (3.1-6.8) 4.0 (2.3-5.5) 4.4 (2.6-5.2) 3.8 (2.5-5.2) 4.2 (2.7-5.2) Female sex, n (%) 12 (40) 13 (41) 15 (48) 3 (21) 8 (50) 19 (45) 89 (55) HIV-positive, n (%) † 0 (0) 0 (0) 1 (3) 2 (14) 0 (0) 4 (9.5) 11 (6.7) Findings at presentation, median (IQR) Axillary temperature 36.6 (36.2-37) 38.5 (38-38.9)*** 38.7 (38.1-39.5)*** 39.2 (38.4-40.0)*** 38.8 (38.2-39.6)*** 39 (38.1-39.8)*** 38.8 (38-39.5)*** Pulse rate, beats/min 108 (102-119) 132 (105-156)* 128 (107-152)* 108 (95-151) 147 (122-160)** 153 (133.5-166)*** 152 (138-171)*** Systolic blood pressure, mm Hg 105 (97-116) 113 (106-122) 108 (102-120) 116 (111-126)* 98 (91-108) 99 (90-107)* 98 (89-109)* Respiratory rate, breaths/min 28 (26-36) 32 (28-36) 29 (26-32) 32 (28-37) 40 (36-59)*** 43 (38-52)*** 44 (36-52)*** Blood glucose, mmol/L 4.9 (4.6-5.6) 4.8 (4.3-5.4) 5.5 (4.6-6.3) 5.4 (5-5.9)* 6.4 (5.1-7.5)* 6.5 (5.7-10.5)*** 6.4 (5.1-7.9)*** Blood lactate, mmol/L 1.8 (1.4-2) 1.4 (1.1-2.1)* 2 (1.3-3) 1.9 (1.6-2.3) 3.5 (2.8-5.5)** 4.2 (2.7-7.3)*** 6.2 (3.7-10.5)*** Hb, g/dL 10.2 (9.0-10.8) 11.6 (11.0-12.3)** 10.2 (9.1-11.6) 10.4 (9.8-11.7) 9.2 (7.6-9.9) 8.9 (7.5-10.5)* 6.5 (5.5-7.8)*** Platelets, ×10 9 /L 435 (309-476) 327 (237-387)** 112 (75-144)*** 270 (157-309)** 254 (119-680)* 138 (56-290)*** 57 (28-92)*** Parasitemia, parasites ×10 3 /μL 0 0 37 (2.9-201)*** 0 0 52 (11-254)*** 73 (14-280)*** Open in a separate window IQR, interquartile range; Hb, hemoglobin. ..

    Enzyme-linked Immunosorbent Assay:

    Article Title: Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children
    Article Snippet: 33 Samples were immediately frozen at −80 ° C. Coagulation tests were determined on an MDA180 analyzer (Stago, France) and activated protein C (aPC) levels by enzyme-capture. .. 33 Plasma and CSF antigens were determined using commercial enzyme-linked immunosorbent assay kits: intracellular adhesion molecule-1 (ICAM-1, DY720; R&D), TM (DY3947; R&D), EPCR (0264; Stago, France), albumin (E80-129; Bethyl Laboratories), F1+2 (Enzygnost F1+2; Dade Behring, Germany), and TATs (Enzygnost TAT micro; Dade Behring). table ft1 table-wrap mode="anchored" t5 caption a7 Healthy controls Mild febrile illness Uncomplicated malaria Febrile controls (CSF samples) Nonmalarial coma Retinopathy-negative CM Retinopathy-positive CM (n = 30) (n = 32) (n = 31) (n = 14) (n = 16) (n = 41) (n = 161) Age, median years (IQR) 4.8 (2.7-8) 3.1 (1.8-5.4)* 5.4 (3.1-6.8) 4.0 (2.3-5.5) 4.4 (2.6-5.2) 3.8 (2.5-5.2) 4.2 (2.7-5.2) Female sex, n (%) 12 (40) 13 (41) 15 (48) 3 (21) 8 (50) 19 (45) 89 (55) HIV-positive, n (%) † 0 (0) 0 (0) 1 (3) 2 (14) 0 (0) 4 (9.5) 11 (6.7) Findings at presentation, median (IQR) Axillary temperature 36.6 (36.2-37) 38.5 (38-38.9)*** 38.7 (38.1-39.5)*** 39.2 (38.4-40.0)*** 38.8 (38.2-39.6)*** 39 (38.1-39.8)*** 38.8 (38-39.5)*** Pulse rate, beats/min 108 (102-119) 132 (105-156)* 128 (107-152)* 108 (95-151) 147 (122-160)** 153 (133.5-166)*** 152 (138-171)*** Systolic blood pressure, mm Hg 105 (97-116) 113 (106-122) 108 (102-120) 116 (111-126)* 98 (91-108) 99 (90-107)* 98 (89-109)* Respiratory rate, breaths/min 28 (26-36) 32 (28-36) 29 (26-32) 32 (28-37) 40 (36-59)*** 43 (38-52)*** 44 (36-52)*** Blood glucose, mmol/L 4.9 (4.6-5.6) 4.8 (4.3-5.4) 5.5 (4.6-6.3) 5.4 (5-5.9)* 6.4 (5.1-7.5)* 6.5 (5.7-10.5)*** 6.4 (5.1-7.9)*** Blood lactate, mmol/L 1.8 (1.4-2) 1.4 (1.1-2.1)* 2 (1.3-3) 1.9 (1.6-2.3) 3.5 (2.8-5.5)** 4.2 (2.7-7.3)*** 6.2 (3.7-10.5)*** Hb, g/dL 10.2 (9.0-10.8) 11.6 (11.0-12.3)** 10.2 (9.1-11.6) 10.4 (9.8-11.7) 9.2 (7.6-9.9) 8.9 (7.5-10.5)* 6.5 (5.5-7.8)*** Platelets, ×10 9 /L 435 (309-476) 327 (237-387)** 112 (75-144)*** 270 (157-309)** 254 (119-680)* 138 (56-290)*** 57 (28-92)*** Parasitemia, parasites ×10 3 /μL 0 0 37 (2.9-201)*** 0 0 52 (11-254)*** 73 (14-280)*** Open in a separate window IQR, interquartile range; Hb, hemoglobin. ..



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    Assessments of mechanisms leading to increased sTM levels following stimulation with S. aureus proteins. HUVEC monolayers were stimulated for 22 h with supernatant of overnight cultures of clinically isolated strains of S. aureus (M37, P08) and α-toxin. sTM was assessed in the host cell culture supernatant of stimulated cells (A). Thrombomodulin gene (THBD) expression in HUVECs after stimulation was assessed by qPCR (B) and total TM levels were measured after cell lysis of stimulated cells (C). LDH and TM were measured in cell culture supernatants after stimulations, with and without addition of 1300 nM broad-spectrum MMP inhibitor Marimastat (MMPI) or 10,6 µM ADAM10 selective inhibitor GI254023X (A10I) (D-E). LDH release measurements indicate cytotoxicity. Quantification of sTM and LDH are given in corrected optical density values. Asterisks indicate statistically significant differences (* = p < 0.05, ** = p < 0.01, *** = p < 0.001) according to ANOVA followed by Fisher’s least significant difference (LSD) post hoc test (A, B, C) or student t-test (D, E). Colors indicate different stimuli and symbols indicate different biological replicates. Direct cleavage of 40 ng rTM by 100 ng rADAM10 (rA10) was evaluated by western blot after 2 h incubation at 37 °C, with or without MMPI or A10I (F). Cleavage products are indicated by arrows at approximately 60 and 40 kDa.

    Journal: Virulence

    Article Title: Staphylococcus aureus toxins mediate endothelial Thrombomodulin release during severe invasive infections

    doi: 10.1080/21505594.2025.2605767

    Figure Lengend Snippet: Assessments of mechanisms leading to increased sTM levels following stimulation with S. aureus proteins. HUVEC monolayers were stimulated for 22 h with supernatant of overnight cultures of clinically isolated strains of S. aureus (M37, P08) and α-toxin. sTM was assessed in the host cell culture supernatant of stimulated cells (A). Thrombomodulin gene (THBD) expression in HUVECs after stimulation was assessed by qPCR (B) and total TM levels were measured after cell lysis of stimulated cells (C). LDH and TM were measured in cell culture supernatants after stimulations, with and without addition of 1300 nM broad-spectrum MMP inhibitor Marimastat (MMPI) or 10,6 µM ADAM10 selective inhibitor GI254023X (A10I) (D-E). LDH release measurements indicate cytotoxicity. Quantification of sTM and LDH are given in corrected optical density values. Asterisks indicate statistically significant differences (* = p < 0.05, ** = p < 0.01, *** = p < 0.001) according to ANOVA followed by Fisher’s least significant difference (LSD) post hoc test (A, B, C) or student t-test (D, E). Colors indicate different stimuli and symbols indicate different biological replicates. Direct cleavage of 40 ng rTM by 100 ng rADAM10 (rA10) was evaluated by western blot after 2 h incubation at 37 °C, with or without MMPI or A10I (F). Cleavage products are indicated by arrows at approximately 60 and 40 kDa.

    Article Snippet: The Human Thrombomodulin DuoSet ELISA (R&D Systems, DY3947) was used according to the manufacturer’s instructions to measure sTM levels.

    Techniques: Isolation, Cell Culture, Expressing, Lysis, Western Blot, Incubation

    Comparison of plasma markers of endothelial cell dysfunction (ICAM 1, Thrombomodulin, P-Selectin). (A) shows results for patients with positive (+) or negative (-) COVID-19 PCR test results. (B) further stratifies results based on low (<1.0 ug/ml FEU) or high (>1.0 ug/ml FEU) D-dimer concentration. Numerical results are summarized in (C) .

    Journal: Frontiers in Immunology

    Article Title: Thromboinflammation Supports Complement Activation in Cancer Patients With COVID-19

    doi: 10.3389/fimmu.2021.716361

    Figure Lengend Snippet: Comparison of plasma markers of endothelial cell dysfunction (ICAM 1, Thrombomodulin, P-Selectin). (A) shows results for patients with positive (+) or negative (-) COVID-19 PCR test results. (B) further stratifies results based on low (<1.0 ug/ml FEU) or high (>1.0 ug/ml FEU) D-dimer concentration. Numerical results are summarized in (C) .

    Article Snippet: Selected biomarkers of endothelial cell dysfunction, including ICAM-1 (Quantikine ELISA, Human ICAM-1/CD54 -specific immunoassay, R&D Systems, Inc., Minneapolis, MN), and thrombomodulin (Quantikine ELISA, Human Thrombomodulin/BDCA-3 immunoassay, R&D Systems, Inc., Minneapolis, MN), as well as platelet and endothelial cell activation, P-selectin (Quantikine ELISA, Human P-Selectin/CD62P immunoassay, R&D Systems, Inc., Minneapolis, MN), were evaluated.

    Techniques: Comparison, Clinical Proteomics, Concentration Assay

    Biomarkers of endothelial cell activation in SARS-CoV-2 infection and controls. (A) vWF:Ag, (B) vWF:RCo, (C) ADAMTS13, (D) thrombomodulin, (E) sEPCR, (F) TFPI, (G) Angiopoietin-1, (H) Angiopoietin-2 and (I) P -selectin plasma concentrations were determined by ELISA in healthy controls and COVID-19 patients. Each symbol correspond one patient. Shaded bars indicate the means, and the lines show the SEM. NS, non-significant; * p < 0.05; ** p < 0.01, *** p < 0.001, **** p < 0.0001 (Kruskall-Wallis test, or Mann-Whitney U test).

    Journal: EClinicalMedicine

    Article Title: Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection

    doi: 10.1016/j.eclinm.2021.101069

    Figure Lengend Snippet: Biomarkers of endothelial cell activation in SARS-CoV-2 infection and controls. (A) vWF:Ag, (B) vWF:RCo, (C) ADAMTS13, (D) thrombomodulin, (E) sEPCR, (F) TFPI, (G) Angiopoietin-1, (H) Angiopoietin-2 and (I) P -selectin plasma concentrations were determined by ELISA in healthy controls and COVID-19 patients. Each symbol correspond one patient. Shaded bars indicate the means, and the lines show the SEM. NS, non-significant; * p < 0.05; ** p < 0.01, *** p < 0.001, **** p < 0.0001 (Kruskall-Wallis test, or Mann-Whitney U test).

    Article Snippet: DUOSet ELISA (enzyme-linked immunosorbent assay) was performed for human angiopoietin-1 (DY623), angiopoietin-2 (DY923), elastase (DY9167), P-selectin/CD62P (DY137), soluble endothelial protein C receptor (sEPCR, DY2245), plasminogen activation inhibitor-1 (PAI-1, DY1786), Tissue Factor Pathway Inhibitor (TFPI, DY2974), thrombomodulin (DY3947), tissue-type plasminogen activator (t-PA, DY7449) (R&D, Minneapolis, MN).

    Techniques: Activation Assay, Infection, Clinical Proteomics, Enzyme-linked Immunosorbent Assay, MANN-WHITNEY

    Univariate and multivariate logistic regression of association of covariates with severe disease.

    Journal: EClinicalMedicine

    Article Title: Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection

    doi: 10.1016/j.eclinm.2021.101069

    Figure Lengend Snippet: Univariate and multivariate logistic regression of association of covariates with severe disease.

    Article Snippet: DUOSet ELISA (enzyme-linked immunosorbent assay) was performed for human angiopoietin-1 (DY623), angiopoietin-2 (DY923), elastase (DY9167), P-selectin/CD62P (DY137), soluble endothelial protein C receptor (sEPCR, DY2245), plasminogen activation inhibitor-1 (PAI-1, DY1786), Tissue Factor Pathway Inhibitor (TFPI, DY2974), thrombomodulin (DY3947), tissue-type plasminogen activator (t-PA, DY7449) (R&D, Minneapolis, MN).

    Techniques:

    Tissue Factor (TF), thrombomodulin and EPCR in the lung of SARS-CoV-2 infection and controls. (A) Control case #1. H&E shows preserved alveolar structures. (B) COVID-19 case #1. H&E shows loss of normal lung architecture and changes associated with the disease. (C) Control case #1. TF expression is minimally detected in the alveolar epithelium. (D) COVID-19 case #1. Marked upregulation of TF in epithelial cells. (E) Control case #1. Preserved thrombomodulin expression in the endothelial cells of alveolar capillaries. (F) COVID-19 case #1. Markedly attenuated staining of thrombomodulin. (G) Control case#1. Preserved EPCR expression in the endothelial cells of larger vessels. (H) COVID-19 case #1. Variable/preserved staining of EPCR in large vessels. The yellow arrows show 3 vessels in consecutive sections of COVID-19 case #1, allowing comparison of similar areas for all immunostains. The red arrows indicate expression of the proteins of interest. All images (x200). Bar represents 100 μm (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).

    Journal: EClinicalMedicine

    Article Title: Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection

    doi: 10.1016/j.eclinm.2021.101069

    Figure Lengend Snippet: Tissue Factor (TF), thrombomodulin and EPCR in the lung of SARS-CoV-2 infection and controls. (A) Control case #1. H&E shows preserved alveolar structures. (B) COVID-19 case #1. H&E shows loss of normal lung architecture and changes associated with the disease. (C) Control case #1. TF expression is minimally detected in the alveolar epithelium. (D) COVID-19 case #1. Marked upregulation of TF in epithelial cells. (E) Control case #1. Preserved thrombomodulin expression in the endothelial cells of alveolar capillaries. (F) COVID-19 case #1. Markedly attenuated staining of thrombomodulin. (G) Control case#1. Preserved EPCR expression in the endothelial cells of larger vessels. (H) COVID-19 case #1. Variable/preserved staining of EPCR in large vessels. The yellow arrows show 3 vessels in consecutive sections of COVID-19 case #1, allowing comparison of similar areas for all immunostains. The red arrows indicate expression of the proteins of interest. All images (x200). Bar represents 100 μm (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).

    Article Snippet: DUOSet ELISA (enzyme-linked immunosorbent assay) was performed for human angiopoietin-1 (DY623), angiopoietin-2 (DY923), elastase (DY9167), P-selectin/CD62P (DY137), soluble endothelial protein C receptor (sEPCR, DY2245), plasminogen activation inhibitor-1 (PAI-1, DY1786), Tissue Factor Pathway Inhibitor (TFPI, DY2974), thrombomodulin (DY3947), tissue-type plasminogen activator (t-PA, DY7449) (R&D, Minneapolis, MN).

    Techniques: Infection, Control, Expressing, Staining, Comparison

    Immunothrombosis and Virchow`s triad in SARS-CoV-2 infection. Multiple mechanisms ( e.g. viral cytopathic, complement activation, NETs, hypoxia, pyroptosis, “cytokine storm”) lead to TF expression in the epithelial cells and possibly other cell types. It also promotes activation of endothelial cells resulting in immunothrombosis with release of NETs (Netosis). Given the tropism of SARS-CoV-2, these events are particularly intense in (but not restricted to) the lungs and creates a marked inflammatory response. This process is dysregulated resulting in an exacerbated coagulation-inflammation-angiogenesis cycle. Excessive thrombin generation overcomes inhibition by local anticoagulants whose functions are impaired due to endothelial cell damage with loss of thrombomodulin and TFPI. As a result fibrin deposition and platelet thrombi occur. Accordingly, 3 component of the Virchow's triad, namely hypercoagulability, endothelium activation, and blood stasis are present in most patients and may predispose to thrombosis. Excess thrombin in the lung may also reach the systemic circulation and is likely neutralized by natural anticoagulants, preventing a consumption coagulopathy, unless superimposed with bacterial sepsis and/or liver dysfunction. This process is typical of a compensated coagulopathy (non-overt DIC) [ , ], with compensatory fibrinolysis explaining elevated D -dimers secondary to plasmin degradation of fibrin. In extreme conditions, impaired microcirculation results in organ failure, high morbidity and mortality.

    Journal: EClinicalMedicine

    Article Title: Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection

    doi: 10.1016/j.eclinm.2021.101069

    Figure Lengend Snippet: Immunothrombosis and Virchow`s triad in SARS-CoV-2 infection. Multiple mechanisms ( e.g. viral cytopathic, complement activation, NETs, hypoxia, pyroptosis, “cytokine storm”) lead to TF expression in the epithelial cells and possibly other cell types. It also promotes activation of endothelial cells resulting in immunothrombosis with release of NETs (Netosis). Given the tropism of SARS-CoV-2, these events are particularly intense in (but not restricted to) the lungs and creates a marked inflammatory response. This process is dysregulated resulting in an exacerbated coagulation-inflammation-angiogenesis cycle. Excessive thrombin generation overcomes inhibition by local anticoagulants whose functions are impaired due to endothelial cell damage with loss of thrombomodulin and TFPI. As a result fibrin deposition and platelet thrombi occur. Accordingly, 3 component of the Virchow's triad, namely hypercoagulability, endothelium activation, and blood stasis are present in most patients and may predispose to thrombosis. Excess thrombin in the lung may also reach the systemic circulation and is likely neutralized by natural anticoagulants, preventing a consumption coagulopathy, unless superimposed with bacterial sepsis and/or liver dysfunction. This process is typical of a compensated coagulopathy (non-overt DIC) [ , ], with compensatory fibrinolysis explaining elevated D -dimers secondary to plasmin degradation of fibrin. In extreme conditions, impaired microcirculation results in organ failure, high morbidity and mortality.

    Article Snippet: DUOSet ELISA (enzyme-linked immunosorbent assay) was performed for human angiopoietin-1 (DY623), angiopoietin-2 (DY923), elastase (DY9167), P-selectin/CD62P (DY137), soluble endothelial protein C receptor (sEPCR, DY2245), plasminogen activation inhibitor-1 (PAI-1, DY1786), Tissue Factor Pathway Inhibitor (TFPI, DY2974), thrombomodulin (DY3947), tissue-type plasminogen activator (t-PA, DY7449) (R&D, Minneapolis, MN).

    Techniques: Infection, Activation Assay, Expressing, Coagulation, Inhibition