title: Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in meningococcal septic shock.
abstract: BACKGROUND
  The plasma level of bacterial lipopolysaccharides (LPS) is associated with activation of the coagulation system, inhibition of fibrinolysis and the nature of the clinical presentation and outcome in patients with meningococcal disease. Tissue factor (TF)-bearing microparticles (MPs) appear to contribute to the pathogenesis of disseminated intravascular coagulation (DIC). The aim of this study was to investigate the relationship between MP-associated TF activity and the level of bacterial LPS in plasma from patients with meningococcal septic shock and meningitis.
  
  
  METHODS
  MPs isolated from citrated plasmas were assessed for TF-dependent activity with both a plasma-based thrombin generation assay (CAT) and whole blood-based thromboelastometry (ROTEM). The LPS level was measured using a chromogenic Limulus amebocyte lysate assay.
  
  
  RESULTS
  MPs obtained from patients with meningococcal septic shock initiated significantly more efficient and TF-dependent thrombin generation in the CAT assay compared to MPs from patients with meningococcal meningitis. Differences in MP-associated TF activity between the septic shock patients and the meningitis patients were also evident when MPs were added to whole blood using ROTEM. The level of plasma LPS in patients with septic shock (range 2-2,100 EU/mL) was correlated with thrombogram parameters in the CAT assay; lagtime (r(s)=-0.84), time to peak (rs=-0.83), peak (r(s)=0.85) and ETP (r(s)=0.83).
  
  
  CONCLUSIONS
  MPs obtained from patients with meningococcal septic shock displayed more efficient TF-dependent thrombin generation and clot formation compared to MPs from meningitis patients. MP-associated TF activity was closely associated with plasma LPS levels in the septic shock group.
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Norway; Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, Norway. Electronic address: m.s.hellum@medisin.uio.no.
authors.forename: Marit
authors.initials: M
authors.lastname: Hellum
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, Norway.
authors.forename: Reidun
authors.initials: R
authors.lastname: Øvstebø
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, Norway.
authors.forename: Berit S
authors.initials: BS
authors.lastname: Brusletto
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Norway; Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, Norway.
authors.forename: Jens P
authors.initials: JP
authors.lastname: Berg
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Norway; Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, Norway; Department of Pediatrics, Oslo University Hospital, Norway.
authors.forename: Petter
authors.initials: P
authors.lastname: Brandtzaeg
authors.affiliation: Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, Norway; Section for Hemostasis and Thrombosis, Department of Medical Biochemistry, Oslo University Hospital, Norway.
authors.forename: Carola E
authors.initials: CE
authors.lastname: Henriksson
mesh_terms: D000293:Adolescent; D000328:Adult; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008585:Meningitis, Meningococcal / Q000097:blood; D008589:Meningococcal Infections / Q000097:blood*; D008875:Middle Aged; D012772:Shock, Septic / Q000097:blood* / Q000382:microbiology; D013925:Thromboplastin / Q000378:metabolism*; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides; D013925:Thromboplastin
keywords: Neisseria meningitidis; lipopolysaccharides (LPS); microparticles; procoagulant activity; septic shock; tissue factor