Neutrophil Extracellular Traps and DNase Activity in Sepsis: Associations with Coagulopathy and Organ Dysfunction

BackgroundNeutrophil extracellular traps (NETs) are extracellular reticular structures released from activated neutrophils. This study investigated the relationships among NET constituents-cell-free DNA (cfDNA), histone H3, and high-mobility group box 1 (HMGB1) protein-as well as deoxyribonuclease (DNase), and the severity of organ dysfunction and coagulopathy in patients with sepsis.MethodsIn this exploratory retrospective study, we analyzed serum samples that were collected prospectively and clinical data of 58 adult patients with sepsis admitted to the Emergency and Critical Care Center of Hokkaido University Hospital between September 2019 and October 2021. Participants were divided into high and low cfDNA groups based on the median cfDNA level upon arrival. NET components and DNase activity were measured using fluorescence assays and enzyme-linked immunosorbent assay (ELISA).ResultsThe high cfDNA group demonstrated significantly elevated Sequential Organ Failure Assessment (SOFA) and disseminated intravascular coagulation (DIC) scores, greater leukocytosis, and more pronounced coagulopathy compared to the low cfDNA group. Serum cfDNA, histone H3, and HMGB1 levels were positively correlated and increased with DIC severity. However, serum DNase activity did not differ significantly between groups, nor did it correlate with NET components, DIC scores, or organ dysfunction severity.ConclusionsIn patients with severe sepsis, elevated levels of NET components were associated with poor clinical outcomes, reflecting enhanced NET formation. However, DNase activity did not influence NET levels or clinical severity. These findings suggest that NET components may serve as useful biomarkers of sepsis severity, while DNase activity appears unrelated to clinical outcomes in this context.