Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in meningococcal septic shock

• Published in: Thrombosis research Vol. 133; no. 3; pp. 507 - 514
• Main Authors: Hellum, Marit, Øvstebø, Reidun, Brusletto, Berit S, Berg, Jens P, Brandtzaeg, Petter, Henriksson, Carola E
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 01.03.2014
• Subjects: Adolescent; Adult; Cell-Derived Microparticles - metabolism; Child; Child, Preschool; Female; Hematology, Oncology and Palliative Medicine; Humans; lipopolysaccharides (LPS); Lipopolysaccharides - blood; Male; Meningitis, Meningococcal - blood; Meningococcal Infections - blood; microparticles; Middle Aged; Neisseria meningitidis; procoagulant activity; septic shock; Shock, Septic - blood; Shock, Septic - microbiology; Thromboplastin - metabolism; tissue factor; Young Adult; ETP; pooled normal plasma; RT; room temperature; septic shock; PS; tissue factor; ttPeak; Escherichia coli; TAT; rotational thromboelastometry; tris-buffered saline w/0.5% v/v bovine serum albumin; LT; N. meningitidis; LPS; thrombin-antithrombin complex; PNP; CSF; lagtime; Limulus amebocyte lysate; TBSA; disseminated intravascular coagulation; microparticle; calibrated automated thrombogram; E. coli; DIC; lipopolysaccharides; MP; endogenous thrombin potential; inter quartile range; microparticles; Neisseria meningitidis; lipopolysaccharides (LPS); IQR; procoagulant activity; EU; phosphatidylserine; TF; endotoxin units; LAL; FPA; CAT; ROTEM; cerebrospinal fluid; time to peak; Fibrinopeptide A
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2013.12.031

Abstract Introduction 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. Materials and 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 (rs = − 0.84), time to peak (rs = − 0.83), peak (rs = 0.85) and ETP (rs = 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.