scholarly journals The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles

PLoS ONE ◽  
2020 ◽  
Vol 15 (10) ◽  
pp. e0240189
Author(s):  
Marcela Rosas ◽  
David A. Slatter ◽  
Samya G. Obaji ◽  
Jason P. Webber ◽  
Jorge Alvarez-Jarreta ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Extracellular Vesicles ◽  
Procoagulant Activity

scholarly journals Effect of MSCs and MSC-Derived Extracellular Vesicles on Human Blood Coagulation

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 258 ◽  
Author(s):  
Denis Silachev ◽  
Kirill Goryunov ◽  
Margarita Shpilyuk ◽  
Olga Beznoschenko ◽  
Natalya Morozova ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Blood Coagulation ◽  
Extracellular Vesicles ◽  
Human Blood ◽  
Annexin V ◽  
Procoagulant Activity ◽  
Human Mscs ◽  
Rotational Thromboelastometry ◽  
Procoagulant Effect ◽  
The Impact

Mesenchymal stem cells (MSCs) have emerged as a potent therapeutic tool for the treatment of a number of pathologies, including immune pathologies. However, unwelcome effects of MSCs on blood coagulation have been reported, motivating us to explore the thrombotic properties of human MSCs from the umbilical cord. We revealed strong procoagulant effects of MSCs on human blood and platelet-free plasma using rotational thromboelastometry and thrombodynamic tests. A similar potentiation of clotting was demonstrated for MSC-derived extracellular vesicles (EVs). To offer approaches to avoid unwanted effects, we studied the impact of a heparin supplement on MSC procoagulative properties. However, MSCs still retained procoagulant activity toward blood from children receiving a therapeutic dose of unfractionated heparin. An analysis of the mechanisms responsible for the procoagulant effect of MSCs/EVs revealed the presence of tissue factor and other proteins involved in coagulation-associated pathways. Also, we found that some MSCs and EVs were positive for annexin V, which implies the presence of phosphatidylserine on their surfaces, which can potentiate clot formation. Thus, we revealed procoagulant activity of MSCs/EVs associated with the presence of phosphatidylserine and tissue factor, which requires further analysis to avoid adverse effects of MSC therapy in patients with a risk of thrombosis.

The Factor VIII Bypassing Activity of Prothrombin Complex Concentrates: The Roles of Factor VIla and of Endothelial Cell Tissue Factor

1991 ◽  
Vol 66 (05) ◽  
pp. 559-564 ◽  
Author(s):  
Jerome M Teitel
Keyword(s):  
Factor Viii ◽  
Tissue Factor ◽  
Factor Viia ◽  
Factor Xa ◽  
Procoagulant Activity ◽  
Tissue Factor Expression ◽  
Prothrombin Complex Concentrates ◽  
Cell Tissue ◽  
Factor Expression ◽  
Necrosis Factor

SummaryAn experimental model incorporating cultured endothelial cells (EC) was used to study the "factor VIII bypassing" activity of prothrombin complex concentrates (PCC), a property exploited in the treatment of hemophiliacs with alloantibodies to factor VIII. Two PCC preparations were ineffective as stimuli of tissue factor expression by EC. However, incubation with a combination of PCC plus endotoxin (lipopolysaccharide, LPS) or tumor necrosis factor (TNF) induced much greater tissue factor expression than was seen in response to either substance alone. PCC expressed an additional direct procoagulant activity at the EC surface, which could not be attributed to either thrombin or factor Xa, and which was diminished by an anti-tissue factor antibody. Therefore factor VIIa, which was detectable in both PCC preparations, likely provided this additional direct procoagulant activity at the EC surface. We also excluded the possibility that coagulation proteases contained in or generated in the presence of PCC are protected from inactivation by AT III. Therefore, PCC can indirectly bypass factor VIII by enhancing induced endothelial tissue factor expression, and also possess direct procoagulant activity, probably mediated by factor VIIa.

Desmopressin (DDAVP) Enhances Platelet Adhesion to the Extracellular Matrix of Cultured Human Endothelial Cells through Increased Expression of Tissue Factor

1997 ◽  
Vol 77 (05) ◽  
pp. 0975-0980 ◽  
Author(s):  
Angel Gálvez ◽  
Goretti Gómez-Ortiz ◽  
Maribel Díaz-Ricart ◽  
Ginés Escolar ◽  
Rogelio González-Sarmiento ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Tissue Factor ◽  
Platelet Adhesion ◽  
Umbilical Vein ◽  
Procoagulant Activity ◽  
Experimental Conditions ◽  
Chromogenic Assay

SummaryThe effect of desmopressin (DDAVP) on thrombogenicity, expression of tissue factor and procoagulant activity (PCA) of extracellular matrix (ECM) generated by human umbilical vein endothelial cells cultures (HUVEC), was studied under different experimental conditions. HUVEC were incubated with DDAVP (1, 5 and 30 ng/ml) and then detached from their ECM. The reactivity towards platelets of this ECM was tested in a perfusion system. Coverslips covered with DD A VP-treated ECMs were inserted in a parallel-plate chamber and exposed to normal blood anticoagulated with low molecular weight heparin (Fragmin®, 20 U/ml). Perfusions were run for 5 min at a shear rate of 800 s1. Deposition of platelets on ECMs was significantly increased with respect to control ECMs when DDAVP was used at 5 and 30 ng/ml (p <0.05 and p <0.01 respectively). The increase in platelet deposition was prevented by incubation of ECMs with an antibody against human tissue factor prior to perfusion. Immunofluorescence studies positively detected tissue factor antigen on DDAVP derived ECMs. A chromogenic assay performed under standardized conditions revealed a statistically significant increase in the procoagulant activity of the ECMs produced by ECs incubated with 30 ng/ml DDAVP (p <0.01 vs. control samples). Northern blot analysis revealed increased levels of tissue factor mRNA in extracts from ECs exposed to DDAVP. Our data indicate that DDAVP in vitro enhances platelet adhesion to the ECMs through increased expression of tissue factor. A similar increase in the expression of tissue factor might contribute to the in vivo hemostatic effect of DDAVP.

scholarly journals Circulating Tissue Factor Procoagulant Activity and Thrombin Generation in Patients with Type 2 Diabetes: Effects of Insulin and Glucose

2007 ◽  
Vol 92 (11) ◽  
pp. 4352-4358 ◽  
Author(s):  
Guenther Boden ◽  
Vijender R. Vaidyula ◽  
Carol Homko ◽  
Peter Cheung ◽  
A. Koneti Rao
Keyword(s):  
Type 2 Diabetes ◽  
Tissue Factor ◽  
Blood Coagulation ◽  
Coagulation Factor ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Coagulation Factor Vii ◽  
Glucose Levels ◽  
Study Protocols

Abstract Context: Type 2 diabetes mellitus (T2DM) is a hypercoagulable state. Tissue factor (TF) is the principal initiator of blood coagulation. Objective: Our objective was to examine the effects of hyperglycemia and hyperinsulinemia on the TF pathway of blood coagulation in T2DM. Design: Three study protocols were used: 1) acute correction of hyperglycemia (with iv insulin) followed by 24 h of euglycemia, 2) 24 h of selective hyperinsulinemia, and 3) 24 h of combined hyperinsulinemia and hyperglycemia. Setting: The study took place at a clinical research center. Study Participants: Participants included 18 T2DM patients and 22 nondiabetic controls. Results: Basal TF-procoagulant activity (TF-PCA), monocyte TF mRNA, plasma coagulation factor VII (FVIIc), and thrombin-anti-thrombin complexes were higher in T2DM than in nondiabetic controls, indicating a chronic procoagulant state. Acutely normalizing hyperglycemia over 2–4 h resulted in a small (∼7%) but significant decline in TF-PCA with no further decline over 24 h. Raising insulin levels alone raised TF-PCA by 30%, whereas raising insulin and glucose levels together increased TF-PCA (by 80%), thrombin-anti-thrombin complexes, and prothrombin fragment 1.2. Plasma FVIIa and FVIIc declined with increases in TF-PCA. Conclusion: We conclude that the combination of hyperglycemia and hyperinsulinemia, common in poorly controlled patients with T2DM, contributes to a procoagulant state that may predispose these patients to acute cardiovascular events.

scholarly journals Investigation of procoagulant activity in extracellular vesicles isolated by differential ultracentrifugation

2018 ◽  
Vol 7 (1) ◽  
pp. 1454777 ◽  
Author(s):  
Thøger Nielsen ◽  
Anne Flou Kristensen ◽  
Shona Pedersen ◽  
Gunna Christiansen ◽  
Søren Risom Kristensen
Keyword(s):  
Extracellular Vesicles ◽  
Procoagulant Activity

Elevated blood plasma levels of tissue factor-bearing extracellular vesicles in patients with atrial fibrillation

2019 ◽  
Vol 173 ◽  
pp. 141-150 ◽  
Author(s):  
Morten Mørk ◽  
Jan J. Andreasen ◽  
Lars H. Rasmussen ◽  
Gregory Y.H. Lip ◽  
Shona Pedersen ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Blood Plasma ◽  
Tissue Factor ◽  
Extracellular Vesicles ◽  
Plasma Levels ◽  
Elevated Blood

scholarly journals Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles

2021 ◽  
Vol 5 (6) ◽  
pp. 1682-1694
Author(s):  
Nadim Tawil ◽  
Rayhaan Bassawon ◽  
Brian Meehan ◽  
Ali Nehme ◽  
Laura Montermini ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Tissue Factor ◽  
Extracellular Vesicles ◽  
Coagulation System ◽  
Platelet Factor ◽  
Increased Risk ◽  
Cell Subpopulations ◽  
Cancer Associated Thrombosis

Abstract Vascular anomalies, including local and peripheral thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of deregulation of the cancer cell genome and epigenome. Although the molecular effectors of these changes are poorly understood, the upregulation of podoplanin (PDPN) by cancer cells has recently been linked to an increased risk for venous thromboembolism (VTE) in GBM patients. Therefore, regulation of this platelet-activating protein by transforming events in cancer cells is of considerable interest. We used single-cell and bulk transcriptome data mining, as well as cellular and xenograft models in mice, to analyze the nature of cells expressing PDPN, as well as their impact on the activation of the coagulation system and platelets. We report that PDPN is expressed by distinct (mesenchymal) GBM cell subpopulations and downregulated by oncogenic mutations of EGFR and IDH1 genes, along with changes in chromatin modifications (enhancer of zeste homolog 2) and DNA methylation. Glioma cells exteriorize their PDPN and/or tissue factor (TF) as cargo of exosome-like extracellular vesicles (EVs) shed from cells in vitro and in vivo. Injection of glioma-derived podoplanin carrying extracelluar vesicles (PDPN-EVs) activates platelets, whereas tissue factor carrying extracellular vesicles (TF-EVs) activate the clotting cascade. Similarly, an increase in platelet activation (platelet factor 4) or coagulation (D-dimer) markers occurs in mice harboring the corresponding glioma xenografts expressing PDPN or TF, respectively. Coexpression of PDPN and TF by GBM cells cooperatively affects tumor microthrombosis. Thus, in GBM, distinct cellular subsets drive multiple facets of cancer-associated thrombosis and may represent targets for phenotype- and cell type–based diagnosis and antithrombotic intervention.

scholarly journals Dissemination of extreme levels of extracellular vesicles: tissue factor activity in patients with severe COVID-19

2021 ◽  
Vol 5 (3) ◽  
pp. 628-634
Author(s):  
Christophe Guervilly ◽  
Amandine Bonifay ◽  
Stephane Burtey ◽  
Florence Sabatier ◽  
Raphaël Cauchois ◽  
...  
Keyword(s):  
Septic Shock ◽  
Tissue Factor ◽  
Extracellular Vesicles ◽  
Severe Disease ◽  
Plasminogen Activator Inhibitor ◽  
Hospitalized Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
Thrombotic Risk ◽  
Public Health Challenges ◽  
Inflammatory State

Abstract Coronavirus disease 2019 (COVID-19) has become one of the biggest public health challenges of this century. Severe forms of the disease are associated with a thrombo-inflammatory state that can turn into thrombosis. Because tissue factor (TF) conveyed by extracellular vesicles (EVs) has been implicated in thrombosis, we quantified the EV-TF activity in a cohort of hospitalized patients with COVID-19 (n = 111) and evaluated its link with inflammation, disease severity, and thrombotic events. Patients with severe disease were compared with those who had moderate disease and with patients who had septic shock not related to COVID-19 (n = 218). The EV-TF activity was notably increased in patients with severe COVID-19 compared with that observed in patients with moderate COVID-19 (median, 231 [25th to 75th percentile, 39-761] vs median, 25 [25th to 75th percentile, 12-59] fM; P &lt; .0001); EV-TF was correlated with leukocytes, D-dimer, and inflammation parameters. High EV-TF values were associated with an increased thrombotic risk in multivariable models. Compared with patients who had septic shock, those with COVID-19 were characterized by a distinct coagulopathy profile with significantly higher EV-TF and EV-fibrinolytic activities that were not counterbalanced by an increase in plasminogen activator inhibitor-1 (PAI-1). Thus, this article is the first to describe the dissemination of extreme levels of EV-TF in patients with severe COVID-19, which supports the international recommendations of systematic preventive anticoagulation in hospitalized patients and potential intensification of anticoagulation in patients with severe disease.

scholarly journals Corrigendum to ‘Microvesicle-associated tissue factor procoagulant activity for the preoperative diagnosis of ovarian cancer”, [Thromb. Res. 141 (2016) 39–48]

2016 ◽  
Vol 146 ◽  
pp. 135 ◽  
Author(s):  
Carlota Claussen ◽  
Alma-Verena Rausch ◽  
Susanne Lezius ◽  
Ali Amirkhosravi ◽  
Monica Davila ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tissue Factor ◽  
Preoperative Diagnosis ◽  
Procoagulant Activity

scholarly journals The stable prostacyclin analog, iloprost, and prostaglandin E1 inhibit monocyte procoagulant activity in vitro

Blood ◽  
1991 ◽  
Vol 78 (2) ◽  
pp. 382-386 ◽  
Author(s):  
DJ Crutchley ◽  
MJ Hirsh
Keyword(s):  
Tissue Factor ◽  
Prostaglandin E1 ◽  
Human Peripheral Blood ◽  
Fold Increase ◽  
Procoagulant Activity ◽  
Factor Vii ◽  
Dependent Inhibition ◽  
Clinical Potential ◽  
Prostacyclin Analog

Abstract Exposure of human peripheral blood to 100 ng/mL of bacterial endotoxin for 2 hours resulted in a 20-fold increase in monocyte procoagulant activity. The activity was functionally identified as tissue factor, because it was not expressed in plasma deficient in factor VII and was specifically inhibited by a monoclonal antibody directed against human tissue factor. When the stable prostacyclin analog, iloprost, was added to blood 30 minutes before endotoxin, a dose-dependent inhibition of monocyte procoagulant activity occurred, with an I50 of 20 nmol/L. Prostaglandin E1 (PGE1) produced similar effects, with an I50 of 150 nmol/L. Exposure of THP-1 monocytic cells to 100 ng/mL endotoxin resulted in a threefold increase in procoagulant activity after 2 hours and a 20-fold increase after 6 hours. A 30-minute pretreatment with iloprost or PGE1 again inhibited development of procoagulant activity, with I50 values of 5 nmol/L and 150 nmol/L, respectively. Treatment of THP-1 cells with iloprost 2 hours after exposure to endotoxin significantly inhibited further increases in procoagulant activity. Iloprost was less potent under these conditions, 30% inhibition being obtained at 100 nmol/L and 70% at 1 mumol/L. These results suggest that prostacyclin may be a physiologic modulator of monocyte tissue factor expression; in addition, its stable analog, iloprost, may have clinical potential for the treatment of thrombotic disorders in which elevated monocyte procoagulant activity plays a role.

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