The effect of corn trypsin inhibitor, anti-tissue factor pathway inhibitor antibodies and phospholipids on microvesicle-associated thrombin generation in patients with pancreatic cancer and healthy controls

Hellum, Marit; Franco-Lie, Isabel; Øvstebø, Reidun; Hauge, Truls; Henriksson, Carola E.

doi:10.1371/journal.pone.0184579

Cited by 19 publications

(23 citation statements)

References 46 publications

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“…For example, the median phosphatidylserine‐mediated procoagulant activity (43 nM) of haemoperitoneum fluids in this study was similar to that reported for plasma from human pancreatic cancer patients (57 nM, sd 44 nM) (Hellum et al . ) and considerably higher than for human patients after liver resection (<20 nM) (Banz et al ). Similarly, the median procoagulant activity of haemoperitoneum fluids is higher than previously reported results for plasma from dogs (median 8.596 nM, range 0 to 49.33) with immune‐mediated haemolytic anaemia, which is well recognised to create a hypercoagulable state (Kidd et al ).…”

Section: Discussionmentioning

confidence: 94%

Extracellular vesicle concentration and procoagulant activity of canine haemoperitoneum fluid and packed red blood cells

Sowy

Rutter

Jeffery

2019

J of Small Animal Practice

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Objectives To compare the concentration of phosphatidylserine‐positive extracellular vesicles and phosphatidylserine‐derived procoagulant activity of canine haemoperitoneum fluids and packed red blood cell units. Materials and Methods Ten dogs with haemoperitoneum (neoplasia = 7; trauma = 1; other = 2) were recruited, and five non‐leukoreduced packed red blood cell units purchased. Supernatants were collected from haemoperitoneum samples and packed red blood cell units using a consistent centrifugation protocol. Phosphatidylserine‐positive extracellular vesicle concentrations were measured by flow cytometry and phosphatidylserine‐mediated procoagulant activity by a commercial thrombin generation assay. Results Phosphatidylserine‐mediated procoagulant activity was significantly higher for supernatants collected from packed red blood cell units (median 54 nM, range 53 to 60 nM) than haemoperitoneum samples (median 43 nM; range 7 to 51 nM; P = 0.0007). By flow cytometry, the concentration of phosphatidylserine‐positive extracellular vesicles was not significantly different between packed red blood cell (median: 415/μL, range 173 to 1331/μL) and haemoperitoneum samples (median: 314/μL, range 132 to 3880/μL; P = 0.77). Clinical Significance This study does not suggest that shed abdominal blood contains more extracellular vesicles with phosphatidylserine‐mediated procoagulant activity than donor packed red blood cell units. Clinical studies to compare the effects of autologous transfusion of shed abdominal blood and packed red blood cell units on coagulation status and clinical outcome are required.

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Section: Discussionmentioning

confidence: 94%

Extracellular vesicle concentration and procoagulant activity of canine haemoperitoneum fluid and packed red blood cells

Sowy

Rutter

Jeffery

2019

J of Small Animal Practice

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“…It is a limitation of our study that no additional functional assays were applied for the quantification procoagulant EVs. For example, modified thrombin generation assays [ 24 , 25 ] or prothrombinase assays [ 26 , 27 ] would have added valuable additional information about the procoagulant properties of EVs in our study population. However, patient material was very limited, and therefore, we could not perform additional measurements.…”

Section: Discussionmentioning

confidence: 99%

Low extracellular vesicle–associated tissue factor activity in patients with persistent lupus anticoagulant and a history of thrombosis

Hell

Posch

et al. 2018

Ann Hematol

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Lupus anticoagulants (LA) are a heterogeneous group of antiphospholipid antibodies (aPLAs) that promote thrombosis. Tissue factor (TF)–bearing extracellular vesicles (EVs) might contribute to the prothrombotic state of patients with persistent LA and a history of thrombosis. To investigate if EV-associated TF activity is elevated in a well-defined group of LA-positive patients with a history of thrombosis in comparison to that of healthy controls. Adult patients (n = 94, median age 40.1 years, interquartile range (IQR) 29.9–53.4; 87% females) positive for LA and a history of thrombosis (78% venous thrombosis, 17% arterial thrombosis, 5% venous thrombosis and arterial thrombosis) and healthy age- and sex-matched controls (n = 30, median age 42.9 years, IQR 38.6–45.8, 77% females) were included in this study. EV-TF activity was determined with a factor Xa generation assay and anti-β2-glycoprotein (anti-β2GPI) and anticardiolipin (aCL) antibodies by enzyme-linked immunoassays. EV-TF activity did not differ between 94 LA-positive patients with a history of thrombosis (median 0.05 pg/mL, IQR 0.00–0.14) and 30 healthy controls (median 0.06, IQR 0.00–0.11, p = 0.7745). No correlation was found between EV-TF activity and lupus-sensitive activated partial thromboplastin time (aPTT-LA) (rho = 0.034), Rosner index (rho = − 0.056), anti-β2GPI IgG (rho = 0.05), anti-β2GPI IgM (rho = − 0.08), aCL IgG (rho = 0.12), and aCL IgM (rho = − 0.11) in LA-positive patients. We found low EV-TF activity levels in LA-positive patients and a history of thrombosis and no correlation with analyzed aPLAs. Our data indicate that circulating TF-bearing EVs do not contribute to the prothrombotic state of patients with LA.

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“…Then, Image Stream X Mk II (Amnis Corporation, Seattle, USA) was used to analyze the MP pro les as described by Headland SE (16). In addition, quantitative determination of MPs by ELISA as described by Hellum M (17). The Zymuphen MP activity assay (Hyphen BioMed, Neuville-sur-Oise, France) was used to determine the activity of phosphatidylserine (PS), which widely exists on the membrane surface of MPs.…”

Section: Quantitative Determination Of Mps By Flow Cytometry and Elisamentioning

confidence: 99%

Synergistic Effects of EMPs and PMPs on Pulmonary Vascular Leakage and Lung Injury After Ischemia/Reperfusion

Li¹,

Zhang²,

Zhu³

et al. 2020

Preprint

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Background Vascular leakage is an important process of critical conditions such as shock and I/R-induced lung injury. Microparticles (MPs), including endothelial cell-derived microparticles (EMPs), platelet-derived microparticles (PMPs) and neutrophil-derived microparticles (NMPs), have been shown to participate in many diseases. Whether these MPs take part in pulmonary vascular leakage and lung injury after ischemia/reperfusion (I/R) and have synergistic and the underlying mechanism are not known.Methods Using hemorrhage/transfusion (Hemo/Trans) and aorta abdominalis occlusion-induced ischemia/reperfusion (I/R) rat models, the role of EMPs, PMPs and NMPs and their relationship and the mechanisms in pulmonary vascular leakage and lung injury were studied.Results The concentrations of EMPs, PMPs and NMPs were significantly increased after I/R. Intravenous administration of EMPs and PMPs but not NMPs induced pulmonary vascular leakage and lung injury. Furthermore, EMPs could induce pulmonary sequestration of platelets and promote more PMP production, and synergistically exacerbate pulmonary vascular leakage. MiR-1, miR-155 and miR-542 in EMP, and miR-126 and miR-29 in PMP, were significantly increased after hypoxia/reoxygenation (H/R). Of which, inhibition of miR-155 in EMPs and miR-126 in PMPs alleviated the detrimental effects of EMPs and PMPs on vascular permeability and lung injury. Overexpression of miR-155 in EMPs down-regulated the expression of ZO-1 and claudin-5, the tight junction related proteins, while overexpression of miR-126 up-regulated the expression of caveolin-1 (Cav-1), the trans-cellular transportation related protein. Inhibiting EMP and PMP production with blebbistatin (BLE) and amitriptyline (AMI) respectively, protected pulmonary vascular permeability and lung injury.Conclusions EMPs and PMPs contribute to the pulmonary vascular leakage and lung injury after I/R. EMPs mediate pulmonary sequestration of platelets, producing more PMPs to play synergistic effect. Mechanically, EMPs carrying miR-155 that targets ZO-1 and claudin-5 and PMPs carrying miR-126 that up-regulates Cav-1, synergistically regulate pulmonary vascular permeability and mediate the lung injury after I/R.

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The effect of corn trypsin inhibitor, anti-tissue factor pathway inhibitor antibodies and phospholipids on microvesicle-associated thrombin generation in patients with pancreatic cancer and healthy controls

Cited by 19 publications

References 46 publications

Extracellular vesicle concentration and procoagulant activity of canine haemoperitoneum fluid and packed red blood cells

Extracellular vesicle concentration and procoagulant activity of canine haemoperitoneum fluid and packed red blood cells

Low extracellular vesicle–associated tissue factor activity in patients with persistent lupus anticoagulant and a history of thrombosis

Synergistic Effects of EMPs and PMPs on Pulmonary Vascular Leakage and Lung Injury After Ischemia/Reperfusion

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