title: Blood levels of histone-complexed DNA fragments are associated with coagulopathy, inflammation and endothelial damage early after trauma.
abstract: BACKGROUND
  Tissue injury increases blood levels of extracellular histones and nucleic acids, and these may influence hemostasis, promote inflammation and damage the endothelium. Trauma-induced coagulopathy (TIC) may result from an endogenous response to the injury that involves the neurohumoral, inflammatory and hemostatic systems.
  
  
  OBJECTIVE
  To study the contribution of extracellular nucleic constituents to TIC, inflammation and endothelial damage.
  
  
  METHODS
  Prospective observational study.
  
  
  METHODS
  We investigated histone-complexed DNA fragments (hcDNA) along with biomarkers of coagulopathy, inflammation and endothelial damage in plasma from 80 trauma patients admitted directly to the Trauma Centre from the scene of the accident. Blood was sampled a median of 68 min (IQR 48-88) post injury. Trauma patients with hcDNA levels >median or ≤median were compared.
  
  
  RESULTS
  Trauma patients with high plasma hcDNA had higher Injury Severity Score (ISS) and level of sympathoadrenal activation (higher adrenaline and noradrenaline) and a higher proportion of prolonged activated partial thromboplastin time (APTT) and higher D-dimer, tissue-type plasminogen activator (tPA), Annexin V and soluble CD40 ligand (sCD40L) concurrent with lower plasminogen activator inhibitor (PAI)-1) and prothrombin fragment (PF) 1 + 2 (all P < 0.05), all indicative of impaired thrombin generation, hyperfibrinolysis and platelet activation. Furthermore, patients with high hcDNA had enhanced inflammation and endothelial damage evidenced by higher plasma levels of terminal complement complex (sC5b-9), IL-6, syndecan-1, thrombomodulin and tissue factor pathway inhibitor (all P < 0.05).
  
  
  CONCLUSIONS
  Excessive release of extracellular histones and nucleic acids seems to contribute to the hypocoagulability, inflammation and endothelial damage observed early after trauma.
authors: Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark ; Department of Surgery, Centre for Translational Injury Research, CeTIR, University of Texas Medical School at Houston, TX, USA.
authors: Pär I
authors: PI
authors: Johansson
authors: Nis A
authors: NA
authors: Windeløv
authors: Lars S
authors: LS
authors: Rasmussen
authors: Anne Marie
authors: AM
authors: Sørensen
authors: Sisse R
authors: SR
authors: Ostrowski
keywords: Coagulopathy; deoxyribonucleic acid; histones; nucleic acids; tissue injury; trauma
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