title: Inhibition of plasmin activity by tranexamic acid does not influence inflammatory pathways during human endotoxemia.
abstract: OBJECTIVE
  Plasmin activates several proinflammatory pathways at the cellular level in vitro. Lipopolysaccharide (LPS) administration to healthy humans results in a rapid generation of plasmin activity, accompanied by activation of a number of inflammatory systems.
  
  
  RESULTS
  To determine the role of early plasmin activity in LPS-induced inflammation in vivo, 16 healthy males received an intravenous bolus injection with LPS (from Escherichia coli, 4 ng/kg) directly preceded by a 30-minute intravenous infusion of tranexamic acid (2 g, n=8), a plasmin activation inhibitor, or placebo (n=8). LPS injection induced marked increases in the plasma levels of D-dimer and plasmin-alpha2-antiplasmin complexes, indicative of plasmin activation and generation, respectively, which were strongly attenuated by tranexamic acid (both P<0.01 versus placebo). However, tranexamic acid did not influence LPS-induced coagulation activation, granulocytosis, neutrophil activation (expression of CD11b, CD66b, and L-selectin) or degranulation (plasma concentrations of elastase-alpha1-antitrypsin and bactericidal permeability-increasing protein), endothelial cell activation (plasma levels of von Willebrand factor and soluble E-selectin), or cytokine release.
  
  
  CONCLUSIONS
  These data argue against a role of early plasmin generation in the subsequent activation of other inflammatory pathways during human endotoxemia.
authors.affiliation: Laboratory of Experimental Internal Medicine, Tropical Medicine & AIDS, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. r.renckens@amc.uva.nl
authors.forename: Rosemarijn
authors.initials: R
authors.lastname: Renckens
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Weijer
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Jennie M
authors.initials: JM
authors.lastname: Pater
authors.forename: Joost C
authors.initials: JC
authors.lastname: Meijers
authors.forename: C Erik
authors.initials: CE
authors.lastname: Hack
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000328:Adult; D000990:Antithrombin III / Q000032:analysis; D001667:Binding, Competitive; D015415:Biomarkers; D016207:Cytokines / Q000097:blood; D019446:Endotoxemia / Q000097:blood*; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005341:Fibrinolysin / Q000096:biosynthesis*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis; D010958:Plasminogen / Q000378:metabolism*; D011516:Prothrombin / Q000032:analysis; D014148:Tranexamic Acid / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D005338:Fibrin Fibrinogen Degradation Products; D008070:Lipopolysaccharides; D010446:Peptide Fragments; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D014148:Tranexamic Acid; D000990:Antithrombin III; D011516:Prothrombin; D010958:Plasminogen; D010447:Peptide Hydrolases; D005341:Fibrinolysin