Prognostic Value of the C‐Reactive Protein × Platelet‐to‐Lymphocyte Ratio for 28‐Day Mortality in Patients With Sepsis: A Retrospective Cohort Study

Background and Aims Inflammatory and hematologic biomarkers are commonly used for early risk assessment in sepsis. The C‐reactive protein × platelet‐to‐lymphocyte ratio (CPL) integrates systemic inflammation, platelet‐related thromboinflammation, and lymphocyte‐associated immune suppression. This study aimed to evaluate the association between log‐transformed CPL (lnCPL) and 28‐day mortality in patients with sepsis and to assess its potential value as an adjunctive risk‐stratification marker. Methods This retrospective cohort study included 630 adult patients with sepsis admitted to the intensive care unit of a tertiary hospital between January 2022 and March 2025. CPL was calculated as CRP × platelet‐to‐lymphocyte ratio and then log‐transformed. The primary outcome was 28‐day all‐cause mortality. Patients were stratified according to lnCPL quartiles, and lnCPL was additionally analyzed as a continuous variable. Multivariable logistic regression, restricted cubic spline analysis, receiver operating characteristic curve analysis, bootstrap internal validation, and admission‐year sensitivity analysis were performed. Results Among 630 patients, 115 died within 28 days, corresponding to a mortality rate of 18.3%. Mortality increased progressively across lnCPL quartiles, from 8.9% in Q1 to 31.6% in Q4. When modeled as a continuous variable, lnCPL was associated with increased 28‐day mortality after adjustment for age, sex, SOFA score, GCS score, mechanical ventilation, CRRT, and AKI (OR = 1.716, 95% CI: 1.402–2.101, p < 0.001). Restricted cubic spline analysis showed a significant non‐linear association between lnCPL and mortality. Bootstrap internal validation showed an optimism‐corrected AUC of 0.685 for lnCPL alone and 0.795 after adding lnCPL to the clinical model. Additional adjustment for admission year did not materially change the association. Conclusion Higher lnCPL was associated with increased 28‐day mortality in patients with sepsis and provided modest incremental discrimination beyond conventional clinical variables. However, because lnCPL overlaps with its inflammatory and hematologic components, it should be interpreted as an adjunctive risk‐stratification marker rather than a standalone independent prognostic tool. Prospective multicenter validation is warranted.