title: Procoagulant tissue factor activity on microparticles is associated with disease severity and bacteremia in febrile urinary tract infections.
abstract: BACKGROUND
  Inhibition of tissue factor, the primary initiator of coagulation in sepsis, attenuates morbidity in primates infused with Escherichia coli. In a human endotoxemia model, microparticles expressing procoagulant TF (MP-TF) are released in blood concurrently with markers of inflammation and coagulation. We investigated whether the release of MP-TF into blood is accompanied by procoagulant and inflammatory changes in patients with E. coli urinary tract infection.
  
  
  METHODS
  In a multicenter cohort study, we determined clinical disease severity using APACHE II scores and measured plasma MP-TF activity, TAT, sE-selectin, sVCAM-1, procalcitonin and monocyte count in blood of 215 patients with community-acquired febrile E. coli urinary tract infections.
  
  
  RESULTS
  Plasma MP-TF activity on admission corresponded with clinical disease severity (APACHE II score; P=0.006) and correlated significantly but weakly with plasma markers of disease severity (sE-selectin, sVCAM-1, procalcitonin). Additionally, median plasma MP-TF activity was higher in patients than in healthy controls (197 vs. 79 fM Xa/min; P<0.0001), and highest in bacteremic patients (325 fM Xa/min). MP-TF activity showed a weak inverse correlation with monocyte count (rs -0.22; P=0.016) and a weak correlation with TAT (rs 0.23, P=0.017). After 3 days of antibiotic treatment, upon resolution of the infection, plasma MP-TF activity and TAT concentrations declined.
  
  
  CONCLUSIONS
  Microparticle-associated procoagulant tissue factor activity is related to disease severity and bacteremia in febrile E. coli UTI patients and may contribute to the prothrombotic state in gram-negative sepsis.
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: F J Sherida H
authors.initials: FJ
authors.lastname: Woei-A-Jin
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Willize E
authors.initials: WE
authors.lastname: van der Starre
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute, 1006 BE Amsterdam, The Netherlands.
authors.forename: Margot E T
authors.initials: ME
authors.lastname: Tesselaar
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Patricia
authors.initials: P
authors.lastname: Garcia Rodriguez
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: van Nieuwkoop
authors.affiliation: Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Rogier M
authors.initials: RM
authors.lastname: Bertina
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
authors.affiliation: Department of Clinical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. Electronic address: s.osanto@lumc.nl.
authors.forename: Susanne
authors.initials: S
authors.lastname: Osanto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000097:blood* / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D004927:Escherichia coli Infections / Q000097:blood* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005334:Fever / Q000097:blood / Q000382:microbiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013925:Thromboplastin / Q000378:metabolism*; D014552:Urinary Tract Infections / Q000097:blood* / Q000382:microbiology / Q000473:pathology; D055815:Young Adult
chemical_list: D013925:Thromboplastin
keywords: Coagulation; Disease severity; Inflammation; Microparticles; Sepsis; Tissue factor