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. Objectives: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. © 2011 International Society on Thrombosis and Haemostasis.