The Diagnostic, Therapeutic and Prognostic Relevance of Neutrophil Extracellular Traps in Polytrauma

Abstract

Neutrophil extracellular traps (NETs) represent a recently discovered polymorphonuclear leukocyte-associated ancient defence mechanism, and they have also been identified as part of polytrauma patients' sterile inflammatory response. This systematic review aimed to determine the clinical significance of NETs in polytrauma, focusing on potential prognostic, diagnostic and therapeutic relevance. The methodology covered all major databases and all study types, but was restricted to polytraumatised humans. Fourteen studies met the inclusion criteria, reporting on 1967 patients. Ten samples were taken from plasma and four from whole blood. There was no standardisation of methodology of NET detection among plasma studies; however, of all the papers that included a healthy control NET, proxies were increased. Polytrauma patients were consistently reported to have higher concentrations of NET markers in peripheral blood than those in healthy controls, but their diagnostic, therapeutic and prognostic utility is equivocal due to the diverse study population and methodology. After 20 years since the discovery of NETs, their natural history and potential clinical utility in polytrauma is undetermined, requiring further standardisation and research.

Keywords: DAMPs; Damage associated molecular patterns; NET; mitochondrial DNA; neutrophil extracellular traps; polytrauma; trauma; trauma centre; traumatic shock.

Figure 1

Selection process of the included publications.

Figure 2

Post-Injury Neutrophil Extracellular Traps (NETs). The presence of intravascular NETs have been demonstrated via the analysis of trauma patient plasma for NET components (DNA and NETs or NETosis-associated proteins). NETosis capacity has been measured in unstimulated or PMA-stimulated neutrophils isolated from trauma patient blood. NET markers have been consistently shown as elevated in trauma patient plasma compared to healthy controls and correlations with coagulation, inflammation, endothelial dysfunction and outcomes of MOF, sepsis and mortality have been found. DNAse and hyperbaric oxygen have been studied as NET-targetted interventions, however the benefits in trauma patients are still unclear. The heterogeneity of study populations, laboratory methods, data analysis and chosen outcomes indicate that further research and standardisation are needed to understand the clinical utility of NETs in trauma patients. Figure created with Biorender.com.