Prognostic significance of nucleated red blood cells in trauma patients

Nucleated red blood cells are early erythroid precursors typically confined to the bone marrow. Their appearance in peripheral blood reflects stress erythropoiesis and has been linked to hypoxia and systemic inflammation. While nucleated red blood cells have prognostic value in sepsis and critical illness, their significance in trauma remains poorly understood. This study aimed to evaluate the prognostic value of nucleated red blood cells during the first 10 days in the intensive care unit following severe trauma, and their association with 30-day mortality. We conducted a retrospective observational cohort study including 1636 adult trauma patients admitted to the Reims Level-1 Trauma Center between January 2019 and March 2025, recorded in the TraumaBase^© registry. Nucleated red blood cell counts were measured daily for the first 10 intensive care unit days. K-means clustering identified four nucleated red blood cell phenotypes based on temporal patterns. Outcomes included 10- and 30-day mortality, incidence of acute respiratory distress syndrome, septic shock, mechanical ventilation, and length of stay. Survival analyses used Cox proportional hazards models adjusted for age, Injury Severity Score, Simplified Acute Physiology Score II, and the Sequential Organ Failure Assessment, and propensity-weighted regression assessed dichotomised nucleated red blood cell status. Nucleated red blood cells were detected in 221 patients (13.5%). Phenotype classification revealed: transient early nucleated red blood cells (phenotype 1), single peak (phenotype 2), multiple intermittent peaks (phenotype 3), and persistent elevation (phenotype 4). Phenotype 2 was associated with reduced 10-day mortality (adjusted hazard ratio 0.06, 95% confidence intervals 0.01-0.46), while phenotype 4 exhibited markedly increased mortality (adjusted hazard ratio 9.6, 95% confidence intervals 2.23-41.4, P < 0.001). Nucleated red blood cell+ patients had higher risks of acute respiratory distress syndrome, septic shock, mechanical ventilation, and 30-day mortality. Kaplan-Meier curves confirmed significant differences in survival across phenotypes (log-rank P < 0.001). Nucleated red blood cell presence, particularly persistent elevation, identifies trauma patients at higher risk of adverse outcomes. Routine, daily nucleated red blood cell monitoring may serve as a simple, low-cost prognostic tool in intensive care unit trauma care. Prospective studies are needed to validate these findings and integrate nucleated red blood cell dynamics into risk stratification.