Histone-Complexed DNA Fragments Levels are Associated with Coagulopathy, Endothelial Cell Damage, and Increased Mortality after Severe Pediatric Trauma

Robert T. Russell, Sarah C. Christiaans, Tate Nice, Morgan Banks, Vincent Mortellaro, Charity Morgan, Amy L Duhachek-Stapelman, Steven J Lisco, Jeffrey D. Kerby, Brant M. Wagener, Mike K. Chen, Jean François Pittet

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background: The release of damage-Associated molecular pattern molecules in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. Methods: We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013 to 2016. Blood samples were collected upon arrival and at 24 h, analyzed for hcDNA, coagulation abnormalities, endothelial damage, and clinical outcome. Platelet aggregation was assessed with impedance aggregometry (Multiplate) and coagulation parameters were assessed by measuring prothrombin time ratio in plasma and the use of viscoelastic techniques (Rotational Thromboelastometry) in whole blood. Results: The median age was 8.3 years, the median injury severity score (ISS) was 20, and overall mortality was 10%. Significantly higher levels of hcDNA were found on admission in patients with severe injury (ISS > 25), coagulopathy, and/or abnormal platelet aggregation. Patients with high hcDNA levels also had significant elevations in plasma levels of syndecan-1, suggesting damage to the endothelial glycocalyx. Finally, significantly higher hcDNA levels were found in non-survivors. Conclusion: hcDNA is released following injury and correlates with coagulopathy, endothelial glycocalyx damage, and poor clinical outcome early after severe pediatric trauma. These results indicate that hcDNA may play an important role in development of coagulation abnormalities and endothelial glycocalyx damage in children following trauma.

Original languageEnglish (US)
Pages (from-to)44-52
Number of pages9
JournalShock
Volume49
Issue number1
DOIs
StatePublished - Jan 1 2018

Fingerprint

Histones
Endothelial Cells
Pediatrics
Mortality
DNA
Glycocalyx
Wounds and Injuries
Injury Severity Score
Platelet Aggregation
Syndecan-1
Thrombelastography
Trauma Centers
Patient Admission
Prothrombin Time
Extracellular Space
Electric Impedance
Observational Studies
Prospective Studies

Keywords

  • Coagulopathy
  • DAMPs
  • histones
  • injury
  • pediatric
  • trauma

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Histone-Complexed DNA Fragments Levels are Associated with Coagulopathy, Endothelial Cell Damage, and Increased Mortality after Severe Pediatric Trauma. / Russell, Robert T.; Christiaans, Sarah C.; Nice, Tate; Banks, Morgan; Mortellaro, Vincent; Morgan, Charity; Duhachek-Stapelman, Amy L; Lisco, Steven J; Kerby, Jeffrey D.; Wagener, Brant M.; Chen, Mike K.; Pittet, Jean François.

In: Shock, Vol. 49, No. 1, 01.01.2018, p. 44-52.

Research output: Contribution to journalArticle

Russell, RT, Christiaans, SC, Nice, T, Banks, M, Mortellaro, V, Morgan, C, Duhachek-Stapelman, AL, Lisco, SJ, Kerby, JD, Wagener, BM, Chen, MK & Pittet, JF 2018, 'Histone-Complexed DNA Fragments Levels are Associated with Coagulopathy, Endothelial Cell Damage, and Increased Mortality after Severe Pediatric Trauma', Shock, vol. 49, no. 1, pp. 44-52. https://doi.org/10.1097/SHK.0000000000000902
Russell, Robert T. ; Christiaans, Sarah C. ; Nice, Tate ; Banks, Morgan ; Mortellaro, Vincent ; Morgan, Charity ; Duhachek-Stapelman, Amy L ; Lisco, Steven J ; Kerby, Jeffrey D. ; Wagener, Brant M. ; Chen, Mike K. ; Pittet, Jean François. / Histone-Complexed DNA Fragments Levels are Associated with Coagulopathy, Endothelial Cell Damage, and Increased Mortality after Severe Pediatric Trauma. In: Shock. 2018 ; Vol. 49, No. 1. pp. 44-52.
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AU - Mortellaro, Vincent

AU - Morgan, Charity

AU - Duhachek-Stapelman, Amy L

AU - Lisco, Steven J

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N2 - Background: The release of damage-Associated molecular pattern molecules in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. Methods: We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013 to 2016. Blood samples were collected upon arrival and at 24 h, analyzed for hcDNA, coagulation abnormalities, endothelial damage, and clinical outcome. Platelet aggregation was assessed with impedance aggregometry (Multiplate) and coagulation parameters were assessed by measuring prothrombin time ratio in plasma and the use of viscoelastic techniques (Rotational Thromboelastometry) in whole blood. Results: The median age was 8.3 years, the median injury severity score (ISS) was 20, and overall mortality was 10%. Significantly higher levels of hcDNA were found on admission in patients with severe injury (ISS > 25), coagulopathy, and/or abnormal platelet aggregation. Patients with high hcDNA levels also had significant elevations in plasma levels of syndecan-1, suggesting damage to the endothelial glycocalyx. Finally, significantly higher hcDNA levels were found in non-survivors. Conclusion: hcDNA is released following injury and correlates with coagulopathy, endothelial glycocalyx damage, and poor clinical outcome early after severe pediatric trauma. These results indicate that hcDNA may play an important role in development of coagulation abnormalities and endothelial glycocalyx damage in children following trauma.

AB - Background: The release of damage-Associated molecular pattern molecules in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. Methods: We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013 to 2016. Blood samples were collected upon arrival and at 24 h, analyzed for hcDNA, coagulation abnormalities, endothelial damage, and clinical outcome. Platelet aggregation was assessed with impedance aggregometry (Multiplate) and coagulation parameters were assessed by measuring prothrombin time ratio in plasma and the use of viscoelastic techniques (Rotational Thromboelastometry) in whole blood. Results: The median age was 8.3 years, the median injury severity score (ISS) was 20, and overall mortality was 10%. Significantly higher levels of hcDNA were found on admission in patients with severe injury (ISS > 25), coagulopathy, and/or abnormal platelet aggregation. Patients with high hcDNA levels also had significant elevations in plasma levels of syndecan-1, suggesting damage to the endothelial glycocalyx. Finally, significantly higher hcDNA levels were found in non-survivors. Conclusion: hcDNA is released following injury and correlates with coagulopathy, endothelial glycocalyx damage, and poor clinical outcome early after severe pediatric trauma. These results indicate that hcDNA may play an important role in development of coagulation abnormalities and endothelial glycocalyx damage in children following trauma.

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