Histone-Complexed DNA Fragments Levels are Associated with Coagulopathy, Endothelial Cell Damage, and Increased Mortality after Severe Pediatric Trauma
| Autor: | Jeffrey D. Kerby, Brant M. Wagener, Tate R. Nice, Mike K. Chen, Amy L. Duhachek-Stapelman, Sarah C. Christiaans, Vincent E. Mortellaro, Robert T. Russell, Jean-Francois Pittet, Morgan E. Banks, Steven J. Lisco, Charity J. Morgan |
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| Rok vydání: | 2018 |
| Předmět: |
Male
medicine.medical_specialty Pathology Abnormal platelet aggregation Enzyme-Linked Immunosorbent Assay 030204 cardiovascular system & hematology Critical Care and Intensive Care Medicine Gastroenterology Histones 03 medical and health sciences Injury Severity Score 0302 clinical medicine Internal medicine Coagulopathy Humans Medicine Prospective Studies Child Prospective cohort study Blood Coagulation Whole blood business.industry Endothelial Cells Infant 030208 emergency & critical care medicine DNA Blood Coagulation Disorders medicine.disease Endothelial stem cell Thromboelastometry Child Preschool Emergency Medicine Wounds and Injuries Female business Pediatric trauma |
| Zdroj: | Shock. 49:44-52 |
| ISSN: | 1540-0514 1073-2322 |
| DOI: | 10.1097/shk.0000000000000902 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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