title: Procoagulatory state in inflammatory bowel diseases is promoted by impaired intestinal barrier function.
abstract: Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragment F1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer and F1+2 measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy ; Department of Biomedical Sciences for Health, University of Milan, 20131 Milan, Italy.
authors.forename: Luca
authors.identifier: 0000-0002-2810-9951
authors.initials: L
authors.lastname: Pastorelli
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, 20131 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Dozio
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, 20131 Milan, Italy.
authors.forename: Laura Francesca
authors.identifier: 0000-0002-9490-3723
authors.initials: LF
authors.lastname: Pisani
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Boscolo-Anzoletti
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, 20131 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Vianello
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Munizio
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Spina
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy.
authors.forename: Gian Eugenio
authors.initials: GE
authors.lastname: Tontini
authors.affiliation: Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre, IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy ; Department of Medical and Surgical Pathophysiology and Transplantations, University of Milan, 20122 Milan, Italy.
authors.forename: Flora
authors.identifier: 0000-0001-7423-9864
authors.initials: F
authors.lastname: Peyvandi
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, 20131 Milan, Italy ; Operative Unit of Laboratory Medicine, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy.
authors.forename: Massimiliano Marco
authors.initials: MM
authors.lastname: Corsi Romanelli
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS Policlinico San Donato, 20097 San Donato Milanese, Italy ; Department of Biomedical Sciences for Health, University of Milan, 20131 Milan, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Vecchi