title: High sCD40L levels early after trauma are associated with enhanced shock, sympathoadrenal activation, tissue and endothelial damage, coagulopathy and mortality.
abstract: BACKGROUND
  Severe injury activates the sympathoadrenal, hemostatic and inflammatory systems, but a maladapted response may contribute to a poor outcome. Soluble CD40L is a platelet-derived mediator that links inflammation, hemostasis and vascular dysfunction.
  
  
  OBJECTIVE
  To investigate the association between the sCD40L level and tissue injury, shock, coagulopathy and mortality in trauma patients.
  
  
  METHODS
  A prospective, observational study of 80 trauma patients admitted to a Level I Trauma Center. Data on demography, biochemistry, Injury Severity Score (ISS) and 30-day mortality were recorded and admission plasma/serum analyzed for sCD40L and biomarkers reflecting sympathoadrenal activation (adrenaline, noradrenaline), tissue/endothelial cell/glycocalyx damage (histone-complexed DNA fragments [hcDNA], Annexin V, thrombomodulin and syndecan-1), coagulation activation/inhibition (PF1.2, TAT-complex, antithrombin, protein C, activated protein C, sEPCR, TFPI, von Willebrand factor [VWF], fibrinogen and factor [F] XIII), fibrinolysis (D-dimer, tissue plasminogen activator [tPA] and plasminogen activator inhibitor-1 [PAI-1]) and inflammation (interleukin-6 [IL-6] and sC5b-9). We compared patients stratified by median sCD40L level and investigated predictive values of sCD40L for mortality.
  
  
  RESULTS
  High circulating sCD40L was associated with enhanced tissue and endothelial damage (ISS, hcDNA, Annexin V, syndecan-1 and sTM), shock (pH, standard base excess), sympathoadrenal activation (adrenaline) and coagulopathy evidenced by reduced thrombin generation (PF1.2), hyperfibrinolysis (D-dimer), increased activated partial thromboplastin time (APTT) and inflammation (IL-6) (all P < 0.05). A higher ISS (P = 0.017), adrenaline (P = 0.049) and platelet count (P = 0.012) and lower pH (P =0.002) were associated with higher sCD40L by multivariate linear regression analysis. High circulating sCD40L (odds ratio [OR] 1.84 [95% CI 1.05-3.23], P = 0.034), high age (P = 0.002) and low Glasgow Coma Score (GCS) pre-hospital (P = 0.002) were independent predictors of increased mortality.
  
  
  CONCLUSIONS
  High early sCD40L levels in trauma patients reflect tissue injury, shock, coagulopathy and sympathoadrenal activation and predict mortality. As sCD40L has pro-inflammatory activity and activates the endothelium, sCD40L may be involved in trauma-induced endothelial damage and coagulopathy.
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Copenhagen, Denmark. per.johansson@rh.regionh.dk
authors.forename: P I
authors.initials: PI
authors.lastname: Johansson
authors.forename: A M
authors.initials: AM
authors.lastname: Sørensen
authors.forename: A
authors.initials: A
authors.lastname: Perner
authors.forename: K-L
authors.initials: KL
authors.lastname: Welling
authors.forename: M
authors.initials: M
authors.lastname: Wanscher
authors.forename: C F
authors.initials: CF
authors.lastname: Larsen
authors.forename: S R
authors.initials: SR
authors.lastname: Ostrowski
mesh_terms: D000311:Adrenal Glands / Q000294:innervation*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D023201:CD40 Ligand / Q000097:blood*; D016009:Chi-Square Distribution; D003718:Denmark / Q000453:epidemiology; D004730:Endothelium, Vascular / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D015601:Injury Severity Score; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012769:Shock / Q000097:blood / Q000209:etiology* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013997:Time Factors; D014193:Trauma Centers; D015854:Up-Regulation; D014947:Wounds and Injuries / Q000097:blood* / Q000150:complications* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D023201:CD40 Ligand