多发伤患者早期高铁蛋白血症：一项多中心队列研究中全身炎症和死亡风险的生物标志物

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

作者信息

Chen Shunyao, Chang Teding, Luo Jialiu, Zhang Cong, Zhang Peidong, Gu Shuaipeng, Lin Zhiqiang, Chen Yujie, Shen Youxie, Dong Liming, Wan Qian, He Liang, Lei Yu, Zhang Zhibiao, Cao Kewen, Lin Jiaying, Xu Di, Zhou Xiaozhong, Yang Zengxiang, Chen Deng, Pan Chunqiu, Tang Zhao-Hui

机构信息

Department of Trauma Surgery, Emergency Surgery and Surgical Critical, Tongji Trauma Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Department of Trauma Surgery, Trauma Center, Xiantao First People's Hospital, Xiantao, 433000, China.

出版信息

Inflamm Res. 2025 Sep 4;74(1):119. doi: 10.1007/s00011-025-02074-9.

DOI:10.1007/s00011-025-02074-9

PMID:40906216

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.

摘要

背景

严重多发伤是全球死亡和残疾的主要原因之一。高铁蛋白血症日益被认为是危重病的生物标志物，但其在多发伤中的预后意义仍未得到充分探索。这项多中心研究调查了多发伤患者血清铁蛋白的时间动态变化及其与全身炎症、器官功能障碍和死亡率的关系。

方法

对来自四个创伤中心的1475例多发伤患者进行前瞻性观察队列分析。在入院第1天和第7天测量血清铁蛋白水平。患者根据铁蛋白阈值分层：<500 ng/ml、500-999 ng/ml、1000-2999 ng/ml和≥3000 ng/ml。结局包括死亡率、重症监护病房住院时间、并发症和器官功能障碍。逻辑回归和ROC分析确定了预测阈值。开发并内部验证了一个整合第1天铁蛋白、铁蛋白变化（Δ铁蛋白）、炎症标志物（IL-6、CRP）和临床评分（SOFA、APACHE II）的预后列线图。

结果

39.3%的患者出现高铁蛋白血症（≥500 ng/mL），死亡率从9.2%（铁蛋白<500）升至66.7%（铁蛋白≥3000）（P<0.001）。在死亡率预测方面，第7天铁蛋白（>655 ng/mL）优于第1天水平（AUC 0.807对0.686），敏感性为68.5%，特异性为87.8%。铁蛋白>1000 ng/mL成为独立的死亡风险因素（OR=1.91，P=0.004），与炎症性高铁蛋白血症标志物（IL-6、CRP）升高、肝/肾功能障碍（AST↑、eGFR↓）和凝血障碍（INR↑）相关。幸存者铁蛋白下降更陡（-233对-146 ng/mL，P<0.001），而非幸存者持续存在高铁蛋白血症。预后列线图对院内死亡率具有很强的鉴别能力（AUC=0.813）且校准良好。决策曲线分析证实，在很宽的概率阈值范围（0.1-0.8）内具有显著的临床净效益。