Exploring the Predictive Value of Neutrophil Extracellular Trap Morphology on Peripheral Blood Smears for Sepsis-Induced Coagulopathy

Background and Aims:Sepsis is a prevalent condition in intensive care units, with nosocomial infections as a significant contributing factor. The associated vascular endothelial injury and coagulation dysfunction, termed sepsis-induced coagulopathy (SIC), exhibit an incidence exceeding 60% and a mortality rate surpassing 30% among septic patients. Early and accurate diagnosis is crucial for treatment and prognosis. Current diagnostic criteria, primarily scoring systems established by the International Society on Thrombosis and Haemostasis (ISTH) and the European Society of Cardiology (ESC), rely mainly on coagulation-related laboratory parameters and do not yet incorporate molecular markers of endothelial cell injury. Recent research has demonstrated that neutrophil extracellular traps (NETs) contribute to the pathogenesis of SIC through mechanisms including vascular wall damage, immunothrombosis, and coagulation dysregulation. Therefore, this study employed morphological analysis of blood cells and statistical methods to investigate the predictive value of NETs for SIC.Methods:This prospective observational study enrolled patients meeting the Sepsis-3.0 diagnostic criteria and ISTH diagnostic criteria for SIC at Wuxi People's Hospital Affiliated to Nanjing Medical University between May 2023 and May 2025. Baseline patient data were recorded. The Quantification of neutrophil-derived smudge cells (a morphological surrogate for NETs) was performed based on peripheral blood smear analysis from automated hematology analyzers upon admission. Circulating NETs levels were quantified using an MPO-DNA ELISA kit in peripheral blood plasma samples collected at admission. Patients were stratified into sepsis and sepsis with coagulopathy (SIC) groups based on the subsequent development of coagulopathy. Peripheral blood cell morphology was observed, and serum NETs levels were measured via ELISA. Binary logistic regression analysis was performed to identify risk factors for developing coagulopathy. Receiver operating characteristic (ROC) curves were constructed to analyze the predictive value of NETs, SOFA score, and antithrombin III (AT-III) for coagulopathy in septic patients.Results:Compared to other coagulation and inflammatory markers, patients who developed coagulopathy within 72 hours of admission (SIC progression group) exhibited significantly higher NETs levels than those who did not (non-SIC group). The area under the curve (AUC) for NETs in predicting SIC occurrence was 0.78, while that for MPO-DNA was 0.68. A combination model incorporating morphological NETs%, AT-III, and SOFA score demonstrated optimal predictive performance, achieving an AUC of 0.91 with an optimal cutoff value of 0.35.Conclusions:NETs represent a novel biomarker for SIC. Observation of peripheral blood smear morphology provides a feasible and rapid (approximately 5 minutes) approach for NETs quantification. Combining NETs with other indicators can optimize the early warning system for sepsis-induced coagulopathy.