Early hyperferritinemia in polytrauma: a biomarker of systemic inflammation and mortality risk in a multicenter cohort study.

Abstract

Background: Severe polytrauma is one of the leading causes of death and disability worldwide. Hyperferritinemia is increasingly recognized as a biomarker of critical illness, yet its prognostic significance in polytrauma remains underexplored. This multicenter study investigates the temporal dynamics of serum ferritin in polytrauma patients and its association with systemic inflammation, organ dysfunction, and mortality.

Methods: A prospective observational cohort of 1475 polytrauma patients from four trauma centers was analyzed. Serum ferritin levels were measured on admission day 1 and day 7. Patients were stratified by ferritin thresholds: < 500 ng/ml, 500-999 ng/ml, 1000-2999 ng/ml, and ≥ 3000 ng/ml. Outcomes included mortality, ICU stay, complications, and organ dysfunction. Logistic regression and ROC analyses identified predictive thresholds. A prognostic nomogram integrating Day 1 ferritin, ferritin change (ΔFerritin), inflammatory markers (IL-6, CRP), and clinical scores (SOFA, APACHE II) was developed and internally validated.

Results: Hyperferritinemia (≥ 500 ng/mL) occurred in 39.3% of patients, with mortality escalating from 9.2% (ferritin < 500) to 66.7% (ferritin ≥ 3000) (P < 0.001). Day 7 ferritin (> 655 ng/mL) outperformed day 1 levels (AUC 0.807 vs. 0.686) in mortality prediction, with 68.5% sensitivity and 87.8% specificity. Ferritin > 1000 ng/mL emerged as an independent mortality risk factor (OR = 1.91, P = 0.004), correlating with elevated inflammatory hyperferritinemia markers (IL-6, CRP), hepatic/renal dysfunction (AST↑, eGFR↓), and coagulopathy (INR↑). Survivors exhibited a steeper ferritin decline (- 233 vs. -146 ng/mL, P < 0.001), while non-survivors sustained hyperferritinemia. The prognostic nomogram demonstrated strong discriminative ability for in-hospital mortality (AUC = 0.813) and good calibration. Decision curve analysis confirmed significant clinical net benefit across a wide probability threshold range (0.1-0.8).

Conclusion: Early hyperferritinemia predicts adverse outcomes in polytrauma, reflecting systemic inflammation and organ failure. Serial ferritin monitoring post-injury enhances risk stratification, offering a pragmatic biomarker for guiding intensive care and targeted interventions.