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Updated: May 4, 2026
Author Spotlight: High-Sensitivity Tissue Factor Activity Assay for Plasma Diagnosis
Published on: December 29, 2023
Microparticle-associated tissue factor activity correlates with plasma levels of bacterial lipopolysaccharides in
Marit Hellum1, Reidun Øvstebø2, Berit S Brusletto2
1Institute of Clinical Medicine, University of Oslo, Norway; Blood Cell Research Group, Section for Research, Department of Medical Biochemistry, Oslo University Hospital, Norway.
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 (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.
Insights
Tissue factor (TF)-bearing microparticles (MPs) in meningococcal septic shock patients show higher TF activity and correlate with lipopolysaccharide (LPS) levels. This contributes to disseminated intravascular coagulation (DIC) and poorer outcomes.
Area of Science:
- Coagulation and Thrombosis Research
- Infectious Disease Pathogenesis
- Microbiology
Background:
- Bacterial lipopolysaccharides (LPS) impact coagulation and fibrinolysis in meningococcal disease.
- Tissue factor (TF)-bearing microparticles (MPs) are implicated in the pathogenesis of disseminated intravascular coagulation (DIC).
Purpose of the Study:
- To investigate the relationship between MP-associated TF activity and plasma LPS levels in patients with meningococcal septic shock and meningitis.
Main Methods:
- MPs were isolated from patient plasma and assessed for TF activity using thrombin generation assay (CAT) and thromboelastometry (ROTEM).
- Plasma LPS levels were quantified using a chromogenic Limulus amebocyte lysate assay.
Main Results:
- MPs from septic shock patients exhibited significantly higher TF-dependent thrombin generation compared to meningitis patients.
- MP-associated TF activity differences were observed between septic shock and meningitis groups using ROTEM.
- Plasma LPS levels in septic shock patients strongly correlated with thrombin generation parameters (lag time, time to peak, peak, and ETP).
Conclusions:
- Patients with meningococcal septic shock display enhanced TF-dependent thrombin generation and clot formation via MPs.
- MP-associated TF activity is closely linked to plasma LPS levels in septic shock patients, highlighting a key mechanism in disease severity.
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