Abstract
BACKGROUND: Sepsis, characterized by immune dysregulation, inflammatory cascades, and coagulation dysfunction, remains a global health challenge with high mortality, particularly in patients with multiple organ dysfunction syndrome (MODS). Existing prognostic tools, such as SOFA and APACHE II scores, are limited by complexity and lack of real-time monitoring, necessitating simple and reliable biomarkers for risk stratification and individualized management. OBJECTIVE: This study aimed to evaluate the prognostic value of the neutrophil-to-lymphocyte-to-platelet ratio (NLPR) for mortality in sepsis patients and explore its potential utility in dynamic risk stratification and treatment optimization. METHODS: We conducted a retrospective cohort study using the MIMIC-IV database (v3.1), including adult sepsis patients meeting Sepsis-3.0 criteria. NLPR was calculated based on neutrophil, lymphocyte, and platelet counts within 24 h of admission. Patients were stratified into quartiles (Q1-Q4) based on NLPR values. Kaplan-Meier survival analysis, Cox regression models, and restricted cubic spline (RCS) analysis were performed to assess NLPR's association with 28-day, 90-day, and 365-day mortality. Subgroup analyses examined NLPR's performance in diverse clinical populations. RESULTS: NLPR was a strong and independent predictor of mortality at all time points. Patients in the highest NLPR quartile (Q4) had significantly higher 28-day (28.22% vs. 12.64%), 90-day (36.82% vs. 18.06%), and 365-day (44.94% vs. 25.58%) mortality compared to the lowest quartile (Q1, all P < 0.001). Cox regression confirmed the independent association of high NLPR with mortality after adjusting for confounders such as age, gender, BMI, and SOFA scores. RCS analysis identified nonlinear relationships between NLPR and mortality, with critical thresholds (e.g.,NLPR = 6.5 for 365-day mortality) providing actionable targets for early risk identification. Subgroup analysis revealed consistent predictive performance across clinical populations, with amplified risks in younger patients, malnourished individuals, and those with acute kidney injury. CONCLUSION: NLPR is a simple, accessible, and robust biomarker for sepsis risk stratification, integrating inflammation and coagulation data. It complements traditional scoring systems, provides actionable thresholds for early intervention, and facilitates dynamic monitoring. These findings underscore NLPR's potential to improve clinical decision-making and outcomes in sepsis management, warranting validation in prospective multicenter studies.