title: Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: A prospective observational study of 404 severely injured patients.
abstract: One third of severely injured patients present with a laboratory-based diagnosis of coagulopathy. This study investigated clinical and biomarker profile of patients with rapid thrombelastography (rTEG) coagulopathy, hypothesizing that sympathoadrenal activation and endothelial damage were drivers of this condition.
  
  
  
  Prospective observational study of 404 trauma patients admitted to a Level 1 US Trauma Center. Patients with admission rTEG and plasma measurements of catecholamines (adrenaline, noradrenaline) and biomarkers reflecting endothelial activation/damage (syndecan-1, thrombomodulin, sE-selectin, sVE-cadherin, nucleosomes) were included. Demography, injury type/severity, physiology, treatment, and inhospital mortality were recorded.
  
  
  
  Patients had a median Injury Severity Score (ISS) of 17, 73% from blunt injury. One third (35%) of the patients had rTEG coagulopathy, which was associated with higher plasma adrenaline, syndecan-1, and nucleosomes (all <0.05), higher transfusion requirements and higher early (<24 hours, 9.3% vs. 2.5%) and late (28 days, 23.8% vs. 13.4%) mortality. By adjusted linear regression analyses, high plasma adrenaline, sVE-cadherin, and syndecan-1 (reflecting sympathoadrenal activation and endothelial cell junction and glycocalyx damage) along with male sex, high ISS, low platelet count and prehospital red blood cell transfusion were independently associated with hypocoagulable rTEG, whereas prehospital plasma and sE-selectin (reflecting endothelial activation) were independently associated with more hypercoagulable rTEG.
  
  
  
  In this cohort of severely injured trauma patients, rTEG coagulopathy was associated with sympathoadrenal activation, endotheliopathy, and excess mortality. High adrenaline and biomarkers reflecting endothelial cell junction and glycocalyx damage were independently associated with hypocoagulability and hyperfibrinolysis. These findings support that sympathoadrenal activation and endotheliopathy contribute to trauma-induced coagulopathy and warrants further studies of endothelial repair management.
  
  
  
  Prognostic, Level III.
authors: From the Section for Transfusion Medicine (S.R.O., H.H.H., J.S., M.G.-B., P.I.J.), Capital Region Blood Bank, Department of Anesthesia (J.S.), Center of Head and Orthopedics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; and Centre for Translational Injury Research (CeTIR) and Department of Surgery (J.C.C., L.A.B., B.A.C., J.B.H., C.E.W., P.I.J.), UT Health, University of Texas Health Science Center at Houston, Houston, Texas.
authors: Sisse R
authors: SR
authors: Ostrowski
authors: Hanne H
authors: HH
authors: Henriksen
authors: Jakob
authors: J
authors: Stensballe
authors: Mikkel
authors: M
authors: Gybel-Brask
authors: Jessica C
authors: JC
authors: Cardenas
authors: Lisa A
authors: LA
authors: Baer
authors: Bryan A
authors: BA
authors: Cotton
authors: John B
authors: JB
authors: Holcomb
authors: Charles E
authors: CE
authors: Wade
authors: Pär I
authors: PI
authors: Johansson
mesh_terms: D000311:Adrenal Glands / Q000294:innervation*; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001778:Blood Coagulation Disorders / Q000209:etiology* / Q000401:mortality; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D017052:Hospital Mortality; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013916:Thrombelastography; D014193:Trauma Centers; D014949:Wounds, Nonpenetrating / Q000097:blood* / Q000150:complications* / Q000401:mortality
chemical_list: D015415:Biomarkers