title: A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients.
abstract: OBJECTIVE
  To investigate the association between markers of acute endothelial glycocalyx degradation, inflammation, coagulopathy, and mortality after trauma.
  
  
  BACKGROUND
  Hyperinflammation and acute coagulopathy of trauma predict increased mortality. High catecholamine levels can directly damage the endothelium and may be associated with enhanced endothelial glycocalyx degradation, evidenced by high circulating syndecan-1.
  
  
  METHODS
  Prospective cohort study of trauma patients admitted to a Level 1 Trauma Centre in 2003 to 2005. Seventy-five patients were selected blindly post hoc from 3 predefined injury severity score (ISS) groups (<16, 16-27, >27). In all patients, we measured 17 markers of glycocalyx degradation, inflammation, tissue and endothelial damage, natural anticoagulation, and fibrinolysis (syndecan-1, IL-6, IL-10, histone-complexed DNA fragments, high-mobility group box 1 (HMGB1), thrombomodulin, von Willebrand factor, intercellular adhesion molecule-1, E-selectin, protein C, tissue factor pathway inhibitor (TFPI), antithrombin, D-dimer, tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), soluble uPA receptor, and plasminogen activator inhibitor-1), hematology, coagulation, catecholamines, and assessed 30-day mortality. Variables were compared in patients stratified according to syndecan-1 median.
  
  
  RESULTS
  Patients with high circulating syndecan-1 had higher catecholamines, IL-6, IL-10, histone-complexed DNA fragments, HMGB1, thrombomodulin, D-dimer, tPA, uPA (all P < 0.05), and 3-fold increased mortality (42% vs. 14%, P = 0.006) despite comparable ISS (P = 0.351). Only in patients with high glycocalyx degradation was higher ISS correlated with higher adrenaline, IL-6, histone-complexed DNA fragments, HMGB1, thrombomodulin, and APTT, lower protein C (all P < 0.05), unchanged TFPI and blunted D-dimer response (P < 0.001) because D-dimer was profoundly increased even at low ISS. After adjusting for age and ISS, syndecan-1 was an independent predictor of mortality (OR: 1.01 [95%CI, 1.00-1.02]; P = 0.043).
  
  
  CONCLUSIONS
  In trauma patients, high circulating syndecan-1, a marker of endothelial glycocalyx degradation, is associated with inflammation, coagulopathy and increased mortality.
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. per.johansson@rh.regionh.dk
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.forename: Jakob
authors.initials: J
authors.lastname: Stensballe
authors.forename: Lars S
authors.initials: LS
authors.lastname: Rasmussen
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000378:metabolism*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis / Q000502:physiology*; D005500:Follow-Up Studies; D019276:Glycocalyx / Q000378:metabolism*; D024243:HMGB1 Protein / Q000097:blood; D006657:Histones / Q000097:blood; D017052:Hospital Mortality; D006801:Humans; D015601:Injury Severity Score; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010343:Patient Admission; D011446:Prospective Studies; D011486:Protein C / Q000378:metabolism*; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000601:surgery*; D016019:Survival Analysis; D053668:Syndecan-1 / Q000097:blood*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D018180:Thrombomodulin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood; D014947:Wounds and Injuries / Q000097:blood* / Q000401:mortality / Q000601:surgery*
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D024243:HMGB1 Protein; D006657:Histones; D015850:Interleukin-6; D011486:Protein C; C508241:SDC1 protein, human; D053668:Syndecan-1; D018180:Thrombomodulin; C036309:fibrin fragment D; D016753:Interleukin-10; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D009638:Norepinephrine; D004837:Epinephrine