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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
- Source :
- PLoS ONE, PLoS ONE, Vol 12, Iss 9, p e0184579 (2017)
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- Circulating microvesicles (MVs) are suggested to be important contributors to cancer-associated thrombosis due to the presence of surface-bound procoagulant molecules like tissue factor (TF) and phosphatidylserine (PS). Pancreatic cancer is considered to be one of the most prothrombotic malignancies. The aim of this study was to describe the impact of analytical variables on MV-associated thrombin generation in patients with pancreatic cancer and in healthy controls. MVs were isolated from citrated plasma and added to pooled normal plasma (PNP). Thrombin generation was measured by the calibrated automated thrombogram. The impact of corn trypsin inhibitor (CTI), anti-tissue factor pathway inhibitor (TFPI) antibodies and phospholipids was described. Antibodies against TF were used to assess TF-dependency, and MV-bound PS activity was measured with the Zymuphen MP-activity kit. MVs from the pancreatic cancer patients displayed higher thrombin generation and higher PS-activity than MVs from the healthy control group, while TF-dependency was observed in only 1 out of 13 patient samples. Adequate thrombin generation-curves were only achieved when CTI was omitted and anti-TFPI antibodies were added to PNP prepared in low contact-activating tubes. Addition of phospholipids reduced the significant differences between the two groups, and should be omitted. This modified thrombin generation assay could be useful for measurement of procoagulant circulating MVs, allowing the contribution from MVs affecting both the intrinsic and the extrinsic pathway to be measured.
- Subjects :
- Male
Physiology
lcsh:Medicine
030204 cardiovascular system & hematology
Pharmacology
Biochemistry
Vascular Medicine
chemistry.chemical_compound
0302 clinical medicine
Cell-Derived Microparticles
Medicine and Health Sciences
Enzyme Inhibitors
lcsh:Science
Phospholipids
Plant Proteins
Multidisciplinary
biology
Microvesicle
Thrombin
Venous Thromboembolism
Phosphatidylserine
Plants
Middle Aged
Lipids
Healthy Volunteers
Body Fluids
Blood
Oncology
Experimental Organism Systems
030220 oncology & carcinogenesis
Female
Anatomy
Antibody
Trypsin Inhibitors
Research Article
medicine.drug
Lipoproteins
Phosphatidylserines
Research and Analysis Methods
Blood Plasma
Antibodies
Thromboplastin
Pancreatic Cancer
03 medical and health sciences
Tissue factor
Model Organisms
Tissue factor pathway inhibitor
Plant and Algal Models
Thromboembolism
Pancreatic cancer
Gastrointestinal Tumors
medicine
Humans
Protease Inhibitors
Grasses
Aged
lcsh:R
Organisms
Biology and Life Sciences
Proteins
Cancers and Neoplasms
medicine.disease
Microvesicles
Maize
Pancreatic Neoplasms
chemistry
Enzymology
biology.protein
lcsh:Q
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, PLoS ONE, Vol 12, Iss 9, p e0184579 (2017)
- Accession number :
- edsair.doi.dedup.....cfb275997e57194a7f241b1766867920