scholarly journals Patients With COVID-19 Have Elevated Levels of Circulating Extracellular Vesicle Tissue Factor Activity That Is Associated With Severity and Mortality

2020 ◽  
Author(s):  
Axel Rosell ◽  
Sebastian Havervall ◽  
Fien von Meijenfeldt ◽  
Yohei Hisada ◽  
Katherina Aguilera ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Tissue Factor ◽  
Severe Disease ◽  
Extracellular Vesicle ◽  
High Rate ◽  
Healthy Controls ◽  
Tissue Factor Activity ◽  
Factor Expression ◽  
D Dimer ◽  
Plasma Markers

Objective: Patients with coronavirus disease 2019 (COVID-19) have a high rate of thrombosis. We hypothesized that severe acute respiratory syndrome coronavirus 2 leads to induction of TF (tissue factor) expression and increased levels of circulating TF-positive extracellular vesicles (EV) that may drive thrombosis. Approach and Results: We measured levels of plasma EV TF activity in 100 patients with COVID-19 with moderate and severe disease and 28 healthy controls. Levels of EV TF activity were significantly higher in patients with COVID-19 compared with controls. In addition, levels of EV TF activity were associated with disease severity and mortality. Finally, levels of EV TF activity correlated with several plasma markers, including D-dimer, which has been shown to be associated with thrombosis in patients with COVID-19. Conclusions: Our results indicate that severe acute respiratory syndrome coronavirus 2 infection induces the release of TF-positive EVs into the circulation that are likely to contribute to thrombosis in patients with COVID-19. EV TF activity was also associated with severity and mortality.

Hemostatic Biomarkers and Venous Thromboembolism Are Associated With Mortality and Response to Chemotherapy in Patients With Pancreatic Cancer

2021 ◽  
Author(s):  
Florian Moik ◽  
Gerald Prager ◽  
Johannes Thaler ◽  
Florian Posch ◽  
Sarah Wiedemann ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tissue Factor ◽  
Palliative Chemotherapy ◽  
Cox Regression ◽  
Extracellular Vesicle ◽  
Hazard Ratio ◽  
Factor Activity ◽  
Tissue Factor Activity ◽  
Pai 1 ◽  
D Dimer

Objective: Pancreatic cancer activates coagulation and increases risk of venous thromboembolism (VTE). We aimed at characterizing the association of hemostatic biomarkers and VTE with mortality and chemotherapy response. Approach and Results: Pancreatic cancer patients (n=145) were included in a prospective, observational cohort study (CATS [Vienna Cancer and Thrombosis Study]). Hemostatic biomarkers (D-dimer, extracellular vesicle–tissue factor activity, prothrombin fragment 1+2, fibrinogen, factor VIII, PAI-1 [plasminogen activator inhibitor 1], sP-selectin [soluble P-selectin], thrombin generation assay) were measured at inclusion. The impact of VTE on overall survival/progression-free survival (OS/PFS) was evaluated by multistate modeling. The association of biomarkers with OS was analyzed by Cox-regression and with PFS and disease control rate in patients initiating palliative chemotherapy (n=95) by Cox-regression and logistic regression. Multivariable analysis included stage, grade, sex, age, performance status, VTE (time-dependent), vascular infiltration/compression, and tumor marker levels (carbohydrate-antigen 19-9, carcinoembryonic antigen). VTE occurrence was associated with shorter OS (transition hazard ratio, 3.40 [95% CI, 2.05–5.64]) and shorter PFS (transition hazard ratio, 2.10 [1.16–3.79]). Median post-VTE OS/PFS in months was 5.5 [2.2–6.5] and 3.0 [1.5–3.9], compared with 13.4 [9.7–16.6] and 7.5 [5.9–9.8] in patients without VTE (both P <0.001). D-dimer, extracellular vesicle–tissue factor activity, PAI-1, and sP-selectin were associated with increased mortality (hazard ratio per doubling, 1.27 [1.00–1.61]; 1.63 [1.14–2.36]; 1.25 [1.06–1.47]; 1.52 [1.05–2.20]). In patients initiating palliative chemotherapy, higher D-dimer predicted shorter PFS (hazard ratio per doubling, 1.27 [1.01–1.60]) and lower disease control rate (odds ratio per doubling, 0.59 [0.36–0.98]). Conclusions: VTE diagnosis is associated with shorter OS and PFS. Higher baseline levels of D-dimer, extracellular vesicle–tissue factor activity, PAI-1, and sP-selectin were independently prognostic for increased mortality, and D-dimer predicted response to palliative chemotherapy.

scholarly journals Induction of tissue factor activity in endothelial cells and monocytes by a modified form of albumin present in normal human plasma

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2888-2895
Author(s):  
KJ Faucette ◽  
CJ Parker ◽  
T McCluskey ◽  
NJ Bernshaw ◽  
GM Rodgers
Keyword(s):  
Endothelial Cells ◽  
Human Plasma ◽  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Factor Activity ◽  
Normal Human Plasma ◽  
Human Endothelial Cells ◽  
Tissue Factor Activity ◽  
Factor Expression ◽  
Normal Human

Molecules that induce tissue factor expression by responsive cells such as endothelial cells and monocytes may be important in the regulation of hemostasis and, perhaps, in mediating certain hemostatic disorders. A constituent of normal human plasma capable of inducing tissue factor activity in human endothelial cells and monocytes has been isolated and identified as a derivative of, or modification associated with albumin. Procoagulant albumin caused a concentration-dependent induction of tissue factor expression by human endothelial cells, but bovine endothelial cells were unresponsive. The dose-response curve developed a plateau phase, indicating that the capacity of endothelial cells to respond to the stimulus was finite. The maximum response induced by the procoagulant albumin was similar to that observed for maximally effective concentrations of endotoxin, interleukin-1, and tumor necrosis factor. Time-course studies showed that procoagulant albumin produced peak activity in 4 to 6 hours. Identification of a procoagulant form of albumin in normal human plasma suggests a potential role for this constituent in regulation of hemostasis.

Longitudinal analysis of extracellular vesicle-associated tissue factor activity in cancer patients

2020 ◽  
Vol 195 ◽  
pp. 215-218
Author(s):  
Eva-Maria Reitter ◽  
Alexandra Kaider ◽  
Gerald Prager ◽  
Cihan Ay ◽  
Ingrid Pabinger ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tissue Factor ◽  
Longitudinal Analysis ◽  
Extracellular Vesicle ◽  
Factor Activity ◽  
Tissue Factor Activity

scholarly journals Extracellular vesicle-associated procoagulant phospholipid and tissue factor activity in multiple myeloma

PLoS ONE ◽  
2019 ◽  
Vol 14 (1) ◽  
pp. e0210835 ◽  
Author(s):  
Thøger Nielsen ◽  
Søren Risom Kristensen ◽  
Henrik Gregersen ◽  
Elena Manuela Teodorescu ◽  
Gunna Christiansen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Tissue Factor ◽  
Extracellular Vesicle ◽  
Factor Activity ◽  
Tissue Factor Activity

scholarly journals Induction of tissue factor activity in endothelial cells and monocytes by a modified form of albumin present in normal human plasma

Blood ◽  
1992 ◽  
Vol 79 (11) ◽  
pp. 2888-2895 ◽  
Author(s):  
KJ Faucette ◽  
CJ Parker ◽  
T McCluskey ◽  
NJ Bernshaw ◽  
GM Rodgers
Keyword(s):  
Endothelial Cells ◽  
Human Plasma ◽  
Tissue Factor ◽  
Tissue Factor Expression ◽  
Factor Activity ◽  
Normal Human Plasma ◽  
Human Endothelial Cells ◽  
Tissue Factor Activity ◽  
Factor Expression ◽  
Normal Human

Abstract Molecules that induce tissue factor expression by responsive cells such as endothelial cells and monocytes may be important in the regulation of hemostasis and, perhaps, in mediating certain hemostatic disorders. A constituent of normal human plasma capable of inducing tissue factor activity in human endothelial cells and monocytes has been isolated and identified as a derivative of, or modification associated with albumin. Procoagulant albumin caused a concentration-dependent induction of tissue factor expression by human endothelial cells, but bovine endothelial cells were unresponsive. The dose-response curve developed a plateau phase, indicating that the capacity of endothelial cells to respond to the stimulus was finite. The maximum response induced by the procoagulant albumin was similar to that observed for maximally effective concentrations of endotoxin, interleukin-1, and tumor necrosis factor. Time-course studies showed that procoagulant albumin produced peak activity in 4 to 6 hours. Identification of a procoagulant form of albumin in normal human plasma suggests a potential role for this constituent in regulation of hemostasis.

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