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Determinants of hypofibrinolysis in patients with digestive tract cancer

INTRODUCTION: Recently, we demonstrated that digestive tract cancer (DTC) is associated with reduced fibrin clot permeability and impaired fibrinolysis. AIM: We investigated determinants of fibrinolysis in DTC patients. MATERIAL AND METHODS: In 44 consecutive patients with DTC and 47 controls matche...

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Autores principales: Gronostaj, Katarzyna, Richter, Piotr, Nowak, Wojciech, Undas, Anetta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Termedia Publishing House 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916237/
https://www.ncbi.nlm.nih.gov/pubmed/27350837
http://dx.doi.org/10.5114/pg.2016.57619
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author Gronostaj, Katarzyna
Richter, Piotr
Nowak, Wojciech
Undas, Anetta
author_facet Gronostaj, Katarzyna
Richter, Piotr
Nowak, Wojciech
Undas, Anetta
author_sort Gronostaj, Katarzyna
collection PubMed
description INTRODUCTION: Recently, we demonstrated that digestive tract cancer (DTC) is associated with reduced fibrin clot permeability and impaired fibrinolysis. AIM: We investigated determinants of fibrinolysis in DTC patients. MATERIAL AND METHODS: In 44 consecutive patients with DTC and 47 controls matched for age, sex, and cardiovascular risk, we evaluated fibrinolysis proteins, platelet activation markers, thrombin formation, together with plasma clot lysis time assays in the absence (CLT) and presence of carboxypeptidase potato inhibitor (CLT CPI) that blocks thrombin activatable fibrinolysis inhibitor (TAFI). RESULTS: In the DTC group CLT (by 22.3%) and CLT CPI (by 27.4%) were longer compared with controls. The DTC patients had higher plasma fibrinolysis inhibitors, plasminogen activator inhibitor 1 (PAI-1) (by 18.2%), TAFI activity (by 17.3%), and antigen (by 11.2%). The patients had markedly increased platelet markers – soluble CD40 ligand (by 338%) and P-selectin (by 97%), together with von Willebrand factor (vWF) antigen (by 61%). Thrombin-antithrombin complexes (TAT) (by 48.7%) and soluble thrombomodulin (sTM) (by 17.2%) were also increased in the DTC group (all p < 0.05). Patients with high-grade tumours (n = 26) compared with remainders (n = 18) had longer CLT, higher tissue-type plasminogen activator antigen, both TAFI antigen and activity levels, vWF, and sTM. Multiple regression analysis after adjustment for potential confounders showed that independent predictors of CLT in DTC patients were TAT, TAFI activity, and vWF. The only independent predictor of CLT CPI was TAT. CONCLUSIONS: Hypofibrinolysis in DTC patients is largely driven by enhanced thrombin generation, TAFI, and endothelial injury.
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spelling pubmed-49162372016-06-27 Determinants of hypofibrinolysis in patients with digestive tract cancer Gronostaj, Katarzyna Richter, Piotr Nowak, Wojciech Undas, Anetta Prz Gastroenterol Original Paper INTRODUCTION: Recently, we demonstrated that digestive tract cancer (DTC) is associated with reduced fibrin clot permeability and impaired fibrinolysis. AIM: We investigated determinants of fibrinolysis in DTC patients. MATERIAL AND METHODS: In 44 consecutive patients with DTC and 47 controls matched for age, sex, and cardiovascular risk, we evaluated fibrinolysis proteins, platelet activation markers, thrombin formation, together with plasma clot lysis time assays in the absence (CLT) and presence of carboxypeptidase potato inhibitor (CLT CPI) that blocks thrombin activatable fibrinolysis inhibitor (TAFI). RESULTS: In the DTC group CLT (by 22.3%) and CLT CPI (by 27.4%) were longer compared with controls. The DTC patients had higher plasma fibrinolysis inhibitors, plasminogen activator inhibitor 1 (PAI-1) (by 18.2%), TAFI activity (by 17.3%), and antigen (by 11.2%). The patients had markedly increased platelet markers – soluble CD40 ligand (by 338%) and P-selectin (by 97%), together with von Willebrand factor (vWF) antigen (by 61%). Thrombin-antithrombin complexes (TAT) (by 48.7%) and soluble thrombomodulin (sTM) (by 17.2%) were also increased in the DTC group (all p < 0.05). Patients with high-grade tumours (n = 26) compared with remainders (n = 18) had longer CLT, higher tissue-type plasminogen activator antigen, both TAFI antigen and activity levels, vWF, and sTM. Multiple regression analysis after adjustment for potential confounders showed that independent predictors of CLT in DTC patients were TAT, TAFI activity, and vWF. The only independent predictor of CLT CPI was TAT. CONCLUSIONS: Hypofibrinolysis in DTC patients is largely driven by enhanced thrombin generation, TAFI, and endothelial injury. Termedia Publishing House 2016-02-02 2016 /pmc/articles/PMC4916237/ /pubmed/27350837 http://dx.doi.org/10.5114/pg.2016.57619 Text en Copyright © 2016 Termedia http://creativecommons.org/licenses/by-nc-sa/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
spellingShingle Original Paper
Gronostaj, Katarzyna
Richter, Piotr
Nowak, Wojciech
Undas, Anetta
Determinants of hypofibrinolysis in patients with digestive tract cancer
title Determinants of hypofibrinolysis in patients with digestive tract cancer
title_full Determinants of hypofibrinolysis in patients with digestive tract cancer
title_fullStr Determinants of hypofibrinolysis in patients with digestive tract cancer
title_full_unstemmed Determinants of hypofibrinolysis in patients with digestive tract cancer
title_short Determinants of hypofibrinolysis in patients with digestive tract cancer
title_sort determinants of hypofibrinolysis in patients with digestive tract cancer
topic Original Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4916237/
https://www.ncbi.nlm.nih.gov/pubmed/27350837
http://dx.doi.org/10.5114/pg.2016.57619
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