The incremental prognostic value of platelet-to-neutrophil and platelet-to-lymphocyte ratios in patients with sepsis: A retrospective cohort study.

ObjectiveThis study aimed to systematically investigate the independent predictive value of the platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio for 28-day all-cause mortality in patients with sepsis and to further evaluate their incremental discriminatory capacity when added to conventional prognostic scoring models.MethodsThis single-center retrospective cohort study involved 287 adult patients diagnosed with sepsis according to the Sepsis-3 criteria. Patients were stratified into high- and low-level groups based on the median values of platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio, and baseline characteristics, and clinical outcomes were compared between groups. Univariate and multivariate Cox proportional hazards regression models were used to assess the independent associations of platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio with 28-day mortality risk. To evaluate predictive performance, multiple models were constructed and compared, including Sequential Organ Failure Assessment score alone, Acute Physiology and Chronic Health Evaluation II score alone, each combined separately with platelet-to-neutrophil ratio or platelet-to-lymphocyte ratio, and a composite model integrating Acute Physiology and Chronic Health Evaluation II, day-3 lactate level, platelet-to-neutrophil ratio, and platelet-to-lymphocyte ratio. Model performance was rigorously assessed using receiver operating characteristic curves, calibration plots, decision curve analysis, integrated discrimination improvement, and net reclassification improvement, enabling a comprehensive evaluation of discrimination, calibration, clinical utility, and the incremental value of novel biomarkers.ResultsMultivariate Cox regression analysis revealed that lower platelet-to-neutrophil ratio (hazard ratio = 0.97, 95% confidence interval: 0.95-0.99, p = 0.012) and higher platelet-to-lymphocyte ratio (hazard ratio = 1.01, 95% confidence interval: 1.01-1.01, p = 0.043) were independently associated with increased 28-day all-cause mortality. Kaplan-Meier survival analysis confirmed significantly higher cumulative mortality in the low-platelet-to-neutrophil ratio and high-platelet-to-lymphocyte ratio groups (log-rank p < 0.05). The composite model incorporating Acute Physiology and Chronic Health Evaluation II, day-3 lactate level, platelet-to-neutrophil ratio, and platelet-to-lymphocyte ratio demonstrated superior predictive accuracy, with an area under the receiver operating characteristic curve (area under the curve) of 0.824 (95% confidence interval: 0.778-0.871), significantly outperforming both the Acute Physiology and Chronic Health Evaluation II only model (area under the curve: 0.746, p < 0.001) and the Sequential Organ Failure Assessment only model (area under the curve: 0.667, p < 0.001). Decision curve analysis showed that this model provided greater clinical net benefit across a broad range of threshold probabilities. Furthermore, both integrated discrimination improvement and net reclassification improvement analyses confirmed statistically significant improvements in discrimination and reclassification accuracy after the inclusion of platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio (both p < 0.001).ConclusionPlatelet-to-neutrophil ratio and platelet-to-lymphocyte ratio are independent predictors of 28-day mortality in patients with sepsis. Incorporating these readily available and cost-effective inflammatory markers into traditional prognostic systems-such as Acute Physiology and Chronic Health Evaluation II-and combining them with dynamic lactate monitoring substantially enhances the discrimination, calibration, and clinical utility of risk prediction models. These findings provide robust evidence supporting the use of platelet-to-neutrophil ratio and platelet-to-lymphocyte ratio for early risk stratification and individualized prognostic assessment in clinical practice.