Tissue factor pathway inhibitor does not influence inflammatory pathways during human endotoxemia

J Infect Dis. 2001 Jun 15;183(12):1815-8. doi: 10.1086/320723. Epub 2001 May 11.


Activation of coagulation induces a proinflammatory response in in vitro and animal experiments. Inhibition of the tissue factor-dependent pathway of coagulation inhibits cytokine release and prevents death in gram-negative sepsis models in primates. This study investigated the influence of blocking the coagulation system by tissue factor pathway inhibitor (TFPI) on endotoxin-induced inflammatory responses in healthy humans. Eight men were studied in a double-blind, randomized, placebo-controlled cross-over study. They received a bolus intravenous injection of 4 ng/kg of endotoxin, followed by a 6-h continuous infusion of either TFPI (0.2 mg/kg/h after a bolus of 0.05 mg/kg) or placebo. Endotoxin induced-activation of coagulation was prevented completely by TFPI. In contrast, TFPI did not influence leukocyte activation, chemokine release, endothelial cell activation, or the acute phase response. Thus, complete prevention of coagulation activation by TFPI does not influence activation of inflammatory pathways during human endotoxemia.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction
  • Adult
  • Anticoagulants / administration & dosage
  • Anticoagulants / pharmacology*
  • Blood Coagulation / drug effects*
  • Chemokines / antagonists & inhibitors
  • Chemokines / metabolism
  • Cross-Over Studies
  • Cytokines / blood
  • Double-Blind Method
  • Endotoxemia / blood
  • Endotoxemia / drug therapy*
  • Endotoxemia / immunology
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Kinetics
  • Leukocytes / immunology
  • Lipopolysaccharides / administration & dosage
  • Lipoproteins / administration & dosage
  • Lipoproteins / pharmacology*
  • Male


  • Anticoagulants
  • Chemokines
  • Cytokines
  • Lipopolysaccharides
  • Lipoproteins
  • lipoprotein-associated coagulation inhibitor