thromboplastin and Meningitis--Meningococcal

Endotoxins are potent activators of the complement system. Formed activated complement factors, in turn, are capable of inducing metabolite production that may be essential in the killing of parasites. However, the products formed may also induce severe damage and cause great pathological changes that can be fatal for the individual infected. In the present review article the interaction of endotoxin with monocytes, granulocytes and endothelial cells, as well as the central role of complement activation will be discussed. Also a method is provided for the detection of cell activation in Neisseria meningitidis infection.

Topics: Animals; Blood Vessels; Endothelium; Endotoxins; Granulocytes; Humans; Meningitis, Meningococcal; Monocytes; Plasminogen Activators; Rabbits; Shwartzman Phenomenon; Thromboplastin

Topics: Anemia, Hemolytic; Blood Coagulation Tests; Disseminated Intravascular Coagulation; Factor XII; Fibrinogen; Fibrinolysis; Heparin; Humans; Liver Diseases; Meningitis, Meningococcal; Phospholipids; Thrombin; Thromboplastin

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.. 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.. 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).. 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.

Topics: Adolescent; Adult; Cell-Derived Microparticles; Child; Child, Preschool; Female; Humans; Lipopolysaccharides; Male; Meningitis, Meningococcal; Meningococcal Infections; Middle Aged; Shock, Septic; Thromboplastin; Young Adult

Neisseria meningitidis causes sepsis with coagulopathy. The present study evaluated the tissue factor (TF)-inducing capacity of bacterial LPS in different presentation forms, i.e. membrane-bound LPS versus purified LPS, and of non-LPS components of N. meningitidis. By using a wild-type N. meningitidis, a mutant N. meningitidis lacking LPS (LPS-deficient N. meningitidis), purified LPS from N. meningitidis and Escherichia coli, we measured TF-expression and TF-activity on human monocytes and microparticles (MPs). The effect of TF-modulators, such as phosphatidylserine (PS), tissue factor pathway inhibitor (TFPI) and recombinant IL-10 (rhIL-10) was investigated. In plasmas from meningococcal patients, fibrinopeptide A (FPA), LPS and IL-10 were quantified. Monocytes and MPs exposed to purified LPS or wild-type N. meningitidis had much higher TF-activity than monocytes and MPs exposed to LPS-deficient N. meningitidis (clot formation assay). Incubation with wild-type N. meningitidis, but also LPS-deficient N. meningitidis, resulted in TF-expression on monocytes (flow cytometry, qRT-PCR). Increased cellular TF-activity is associated with coincident surface-exposure of PS and the number of monocytes positive for both PS and TF was significantly higher for monocytes exposed to wild-type N. meningitidis (7.6%) compared with monocytes exposed to LPS-deficient N. meningitidis (1.8%). Treatment with rhIL-10 reduced monocyte- and MP-associated TF-activity, the number of monocytes positive for both TF and PS, and microvesiculation. Patients with meningococcal septicemia had significantly higher levels of LPS, FPA and IL-10 than patients with distinct meningitis. Our results indicate that LPS from N. meningitidis is crucial for inducing TF-activity, but not for monocyte- and MP-associated TF-expression. TF-activity seems to require coincident expression of TF and PS on monocytes, and LPS induces such double-positive monocytes.

Topics: Blood Coagulation; Cell-Derived Microparticles; Cells, Cultured; Escherichia coli; Escherichia coli Infections; Fibrinopeptide A; Gene Expression Regulation, Bacterial; Humans; Interleukin-10; Lipopolysaccharides; Lipoproteins; Meningitis, Meningococcal; Meningococcal Infections; Monocytes; Neisseria meningitidis, Serogroup B; Phosphatidylserines; Thromboplastin

Disseminated intra-vascular coagulation (DIC) is a serious and frequently fatal condition associated with gross abnormalities of thrombosis, haemostasis, vascular function and inflammation. We measured serial levels of plasma soluble E selectin (marking endothelia damage), interleukin 6 (IL-6, a marker if inflammation) and tissue factor (involved in coagulation) in two young adults with bacterially-induced DIC. Soluble E selectin and IL-6 were grossly elevated on presentation and increased as the DIC progressed. Tissue factor was normal on admission but also increased with the DIC. However, levels remained high in one of the patients who subsequently died, whilst levels resolved in the patient who survived. We suggest that both admission and evolving sE-selectin and IL-6 levels may be useful in predicting outcome, and that measurement of TF has little extra to offer.

Topics: Adult; Biomarkers; Disease Progression; Disseminated Intravascular Coagulation; E-Selectin; Endothelium, Vascular; Female; Humans; Interleukin-6; Male; Meningitis, Meningococcal; Meningococcal Infections; Prognosis; Sepsis; Shock, Septic; Thromboplastin

We have evaluated the quantitative relationship between lipopolysaccharide (LPS, endotoxin), fibrinopeptide A (FPA), antithrombin (AT), protein C (PC) and extrinsic pathway inhibitor (EPI) in plasma from 39 consecutively admitted patients with systemic meningococcal disease (SMD). The most severely ill patients with fulminant meningococcal septicemia (n = 13, 6 dead) had significantly (p less than 0.01) higher plasma levels of LPS and FPA and lower levels of PC and AT on admission as compared with the less severe clinical presentations (n = 26, 1 dead). The levels of EPI on admission were significantly (p less than 0.05) higher in nonsurvivors vs survivors with fulminant septicemia. As the disease progressed, the levels of LPS, FPA, AT and PC declined, while the levels of EPI increased. Three of six nonsurviving septicemic patients had levels of EPI greater than 200% within 16 hours of admission vs two of 30 survivors (p = 0.02). The results suggest that increasing levels of LPS in SMD elicit increasing consumption coagulopathy, contributing to the organ pathophysiology. The kinetics of EPI, inhibiting the thromboplastin-FVIIa-FXa complex, differs markedly from the kinetics of AT and PC i.e. increases as opposed to decreases.

Topics: Antithrombin III; Disseminated Intravascular Coagulation; Endotoxins; Factor VII; Fibrinogen; Fibrinopeptide A; Humans; Lipopolysaccharides; Lipoproteins; Meningitis, Meningococcal; Meningococcal Infections; Multiple Organ Failure; Neisseria meningitidis; Protein C; Sepsis; Thromboplastin

Topics: Blood Coagulation Disorders; Child; Erythrocyte Aggregation; Female; Humans; Infant; Infant, Newborn; Kidney Cortex Necrosis; Male; Meningitis, Meningococcal; Renal Veins; Thrombocytopenia; Thrombophlebitis; Thromboplastin