Association between immature platelet fraction measured at ventilator-associated pneumonia diagnosis and 28-day mortality: a prospective observational study

Background Ventilator-associated pneumonia (VAP) is associated with substantial intensive care unit mortality. This study examined whether immature platelet fraction (IPF), measured at VAP diagnosis, was associated with 28-day mortality. Methods This prospective single-centre cohort reports the registered secondary prognostic. objective among adults with microbiologically confirmed VAP. IPF and Sequential Organ Failure Assessment (SOFA) score were assessed at VAP diagnosis; Acute Physiology and Chronic Health Evaluation II (APACHE II) reflected physiology during the first 24 h of ICU admission. The outcome was 28-day all-cause mortality. Because only 21 deaths occurred, the primary analysis was univariable and adjusted analyses were restricted to two-variable sensitivity models. Results Forty-one patients were included and 21 (51.2%) died within 28 days. IPF was higher in non-survivors than survivors [median (IQR), 4.10 (2.40–5.50)% vs. 1.75 (1.38–3.10)%; p = 0.003]. Each 1-percentage-point increase in IPF was associated with higher odds of mortality (OR 1.80, 95% CI 1.16–2.78; p = 0.008). The estimate was similar in a two-variable sensitivity model containing SOFA at VAP diagnosis (OR 1.82, 95% CI 1.15–2.87; p = 0.011). Septic shock was documented within 24 h after VAP diagnosis in 21/21 (100.0%) non-survivors and 11/20 (55.0%) survivors. In the exploratory Firth model containing septic shock, the shock estimate was extremely imprecise (OR 123.3, 95% CI 2.48–6133), precluding inference that the IPF association was independent of shock severity. IPF showed moderate discrimination (AUC 0.773, 95% CI 0.620–0.926), and adding SOFA did not materially improve apparent discrimination (AUC 0.777; p = 0.597 vs. IPF alone). Conclusions Higher IPF at microbiologically confirmed VAP diagnosis was associated with 28-day mortality in this small prospective cohort. However, the marked overlap with septic shock, high overall illness severity, incomplete measurement of infection- and treatment-related confounders, and wide confidence intervals prevent separation of the IPF association from systemic disease severity. Independent or incremental prognostic value was not established; the findings are preliminary and hypothesis-generating. Trial registration ClinicalTrials.gov (NCT07013032), first posted June 10, 2025 study start July 1, 2025. This report addresses the registered secondary mortality objective.