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. 2022 Sep 16;11(18):5438.
doi: 10.3390/jcm11185438.

Extreme Hyperferritinemia: Causes and Prognosis

Maxime Fauter  1   2 , Sabine Mainbourg  3   4   5 , Thomas El Jammal  1 , Arthur Guerber  1 , Sabine Zaepfel  6 , Thomas Henry  2 , Mathieu Gerfaud-Valentin  1 , Pascal Sève  1   7 , Yvan Jamilloux  1   2   5
Affiliations

Extreme Hyperferritinemia: Causes and Prognosis

Maxime Fauter et al. J Clin Med. .

Abstract

The significance of extreme hyperferritinemia and its association with certain diagnoses and prognoses are not well characterized. We performed a retrospective analysis of adult patients with at least one total serum ferritin (TSF) measurement ≥ 5000 µg/L over 2 years, in three university hospitals. Conditions associated with hyperferritinemia were collected, and patients were classified into 10 etiological groups. Intensive care unit (ICU) transfer and mortality rates were recorded. A total of 495 patients were identified, of which 56% had a TSF level between 5000 and 10,000 µg/L. There were multiple underlying causes in 81% of the patients. The most common causes were infections (38%), hemophagocytic lymphohistiocytosis (HLH, 18%), and acute hepatitis (14%). For TSF levels > 10,000 µg/L, there were no solid cancer or hematological malignancy without another cause of hyperferritinemia. Isolated iron-overload syndromes never exceeded TSF levels > 15,000 µg/L. Extreme hyperferritinemia (TSF levels > 25,000 µg/L) was associated with only four causes: HLH, infections, acute hepatitis and cytokine release syndromes. A total of 32% of patients were transferred to an ICU, and 28% died. Both ICU transfer rate and mortality were statistically associated with ferritin levels. An optimized threshold of 13,405 μg/L was the best predictor for the diagnosis of HLH, with a sensitivity of 76.4% and a specificity of 79.3%. Hyperferritinemia reflects a variety of conditions, but only four causes are associated with extreme hyperferritinemia, in which HLH and acute hepatitis are the most common. Extreme hyperferritinemia has a poor prognosis with increased mortality.

Keywords: ferritin; hemophagocytic lymphohistiocytosis; hyperferritinemia; hyperferritinemic syndrome; septic shock.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Distribution of the primary causes of hyperferritinemia according to total serum ferritin levels. The number of the patients in each group is indicated.
Figure 2
Figure 2
Probability of ICU transfer (a) and survival probability (b) according to total serum ferritin levels.
See this image and copyright information in PMC

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