Sympathoadrenal activation and endotheliopathy are drivers of hypocoagulability and hyperfibrinolysis in trauma: A prospective observational study of 404 severely injured patients

• Published in: The journal of trauma and acute care surgery Vol. 82; no. 2; pp. 293 - 301
• Main Authors: Ostrowski, Sisse R, Henriksen, Hanne H, Stensballe, Jakob, Gybel-Brask, Mikkel, Cardenas, Jessica C, Baer, Lisa A, Cotton, Bryan A, Holcomb, John B, Wade, Charles E, Johansson, Pär I
• Format: Journal Article
• Language: English
• Published: United States 01-02-2017
• Subjects: Adrenal Glands - innervation; Adult; Biomarkers - blood; Blood Coagulation Disorders - etiology; Blood Coagulation Disorders - mortality; Endothelium, Vascular - pathology; Female; Fibrinolysis - physiology; Hospital Mortality; Humans; Injury Severity Score; Male; Middle Aged; Prognosis; Prospective Studies; Sympathetic Nervous System - physiopathology; Thrombelastography; Trauma Centers; Wounds, Nonpenetrating - blood; Wounds, Nonpenetrating - complications; Wounds, Nonpenetrating - mortality
• ISSN: 2163-0755; 2163-0763
• DOI: 10.1097/TA.0000000000001304

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.