title: Coagulopathy, catecholamines, and biomarkers of endothelial damage in experimental human endotoxemia and in patients with severe sepsis: a prospective study.
abstract: OBJECTIVE
  The aim of this study was to investigate associations between circulating catecholamines, endothelial damage, and coagulopathy in experimental human endotoxemia and septic patients.
  
  
  METHODS
  Nine healthy male volunteers undergoing endotoxemia (4-hour 0.5 ng/kg/hour infusion of E. coli lipopolysaccharide, blood sampling at 0, 4, and 6 hours) and 20 patients with severe sepsis. Analysis of plasma biomarkers (adrenaline, noradrenaline, thrombomodulin, syndecan-1, soluble vascular endothelial cadherin, histone-complexed DNA fragments, soluble CD40 ligand [sCD40L], protein C, tissue-type plasminogen activator, plasminogen activator inhibitor 1) and routine coagulation tests.
  
  
  RESULTS
  Endotoxemia increased heart rate, temperature, white blood cell count, C-reactive protein and procalcitonin, decreased blood pressure and induced a hemostatic response with platelet consumption, reduced protein C and sCD40L levels and enhanced tissue-type plasminogen activator release (all P<.05). Septic patients had increased levels of noradrenaline, syndecan-1, thrombomodulin, histone-complexed DNA and sCD40L but reduced soluble vascular endothelial cadherin and plasminogen activator inhibitor 1 (all P<.05) and plasma catecholamines correlated positively with syndecan-1 (adrenaline and noradrenaline) and sTM (only noradrenaline) (all P<.05), biomarkers reflecting endothelial damage. Furthermore, noradrenaline, syndecan-1 and thrombomodulin levels correlated with INR and disease severity scores (noradrenaline and thrombomodulin) (all P<.05).
  
  
  CONCLUSIONS
  Experimental endotoxemia induced a discrete hemostatic response without sympathoadrenal activation or endothelial damage. Septic patients had high levels of catecholamines and endothelial damage biomarkers that correlated with each other and with markers of hypocoagulability and disease severity.
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: sisse.ostrowski@gmail.com.
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: Ronan M G
authors.initials: RM
authors.lastname: Berg
authors.forename: Nis A
authors.initials: NA
authors.lastname: Windeløv
authors.forename: Martin A S
authors.initials: MA
authors.lastname: Meyer
authors.forename: Ronni R
authors.initials: RR
authors.lastname: Plovsing
authors.forename: Kirsten
authors.initials: K
authors.lastname: Møller
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001778:Blood Coagulation Disorders / Q000097:blood*; D002395:Catecholamines / Q000097:blood*; D019446:Endotoxemia / Q000097:blood*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D002395:Catecholamines
keywords: Adrenaline; Catecholamines; Coagulopathy; Endothelium; Endotoxemia; Noradrenaline; Sepsis; Syndecan-1; Thrombomodulin; Trauma