Journal of Emergencies, Trauma, and Shock
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ORIGINAL ARTICLE
Year : 2013  |  Volume : 6  |  Issue : 3  |  Page : 171-175

Blood levels of histone-complexed DNA fragments are associated with coagulopathy, inflammation and endothelial damage early after trauma


1 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
2 Department of Anesthesia, Centre for Head and Orthopedic, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark
3 Department of Anesthesia; Trauma Center 3193, Centre for Head and Orthopedic, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK.2100 Copenhagen, Denmark
4 Section for Transfusion Medicine, Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark

Correspondence Address:
Pär I Johansson
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

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Source of Support: This work was supported by The Danish Council for Independent Research (Medical Sciences), The Lundbeck Foundation, Aase and Ejnar Danielsens Foundation, L. F. Foghts Foundation, A. P. Møller and wife Chastine Mc-Kinney Møllers Foundation (Medical Sciences), Haemonectics Corp (MA, USA) and University of Copenhagen (Faculty of Health Sciences), Conflict of Interest: None


DOI: 10.4103/0974-2700.115327

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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. Aims: To study the contribution of extracellular nucleic constituents to TIC, inflammation and endothelial damage. Setting and Design: Prospective observational study. Materials and 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.


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