Endotoxin-Induced Activation of the Coagulation Cascade in Humans
| Autor: | Bernd Jilma, Ursula Hollenstein, L. Dzirlo, Wolfgang Speiser, Hans-Georg Eichler, Petra Stohlawetz, Stylianos Kapiotis, Thomas Pernerstorfer |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Adult
Lipopolysaccharides Neutrophils Antithrombin III Factor VIIa Pharmacology Fibrinogen Monocytes Fibrin Thromboplastin Leukocyte Count Tissue factor chemistry.chemical_compound Double-Blind Method Fibrinolytic Agents medicine Humans Platelet Platelet activation Antigens Protein Precursors Blood Coagulation Acetaminophen Aspirin biology Factor VII Platelet Count Chemistry NF-kappa B Analgesics Non-Narcotic Peptide Fragments Solubility Coagulation Immunology biology.protein Prothrombin Cardiology and Cardiovascular Medicine Dimerization Protein C medicine.drug |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 19:2517-2523 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/01.atv.19.10.2517 |
| Popis: | Abstract —During Gram-negative septic shock, lipopolysaccharide (LPS, endotoxin) induces tissue factor (TF) expression. TF expression is mediated by nuclear factor κB and amplified by activated platelets. TF forms a highly procoagulant complex with activated coagulation factor VII (FVIIa). Hence, we hypothesized that aspirin, which inhibits LPS-induced, nuclear factor κB–dependent TF expression in vitro and platelet activation in vivo, may suppress LPS-induced coagulation in humans. Therefore, we studied the effects of aspirin on systemic coagulation activation in the established and controlled setting of the human LPS model. Thirty healthy volunteers were challenged with LPS (4 ng/kg IV) after intake of either placebo or aspirin (1000 mg). Acetaminophen (1000 mg) was given to a third group to control for potential effects of antipyresis. Neither aspirin nor acetaminophen inhibited LPS-induced coagulation. However, LPS increased the percentage of circulating TF + monocytes by 2-fold. This increase was associated with a decrease in FVIIa levels, which reached a minimum of 50% 24 hours after LPS infusion. Furthermore, LPS-induced thrombin generation increased plasma levels of circulating polymerized, but not cross-linked, fibrin (ie, thrombus precursor protein), whereas levels of soluble fibrin were unaffected. In summary, a single 1000-mg dose of aspirin did not decrease LPS-induced coagulation. However, our study showed, for the first time, that LPS increases TF + monocytes, substantially decreases FVIIa levels, and enhances plasma levels of thrombus precursor protein, which may be a useful marker of fibrin formation in humans. |
| Databáze: | OpenAIRE |
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