High Ferritin Interpreter: Iron Overload or Something Else?
High Ferritin Interpreter: Iron Overload or Something Else?
Work out what a raised ferritin means. Transferrin saturation is the fork: raised with a raised ferritin points to iron overload and testing for HFE haemochromatosis; normal points to inflammation, alcohol, liver disease, metabolic syndrome or malignancy, which cause most high ferritins. Very high values raise HLH and Still’s disease. Thresholds from the 2018 British Society for Haematology and 2022 EASL guidelines — including where they disagree.
Why is the ferritin high?
Ferritin + transferrin saturation + context → iron overload or notA 52-year-old man with a BMI of 33 and a fatty liver on ultrasound has a ferritin of 820 µg/L and a transferrin saturation of 32%. He drinks little alcohol and is well.
The fork
Transferrin saturation raised: men above 50% (both); women above 40% (BSH) or above 45% (EASL)
Both raised → HFE genotype. Ferritin above 1000 µg/L → assess the liver for fibrosis
TSAT normal → look for inflammation, alcohol, liver disease, metabolic syndrome, malignancy, dialysis
- TSAT
- transferrin saturation = serum iron ÷ total iron-binding capacity × 100
- HFE
- the gene behind most haemochromatosis in people of northern European ancestry (C282Y)
- HLH
- haemophagocytic lymphohistiocytosis; ferritin of 500 µg/L or more is one HLH-2004 criterion
Worked example
A 52-year-old man with a BMI of 33 and a fatty liver on ultrasound has a ferritin of 820 µg/L and a transferrin saturation of 32%. He drinks little alcohol and is well.
Ferritin 820 is above the 300 µg/L threshold for men (2.7 times it)
TSAT 32% is not above 50% → not the pattern of iron overload
Not acutely ill; ferritin not above 1000
Metabolic syndrome with fatty liver is the likely cause; HFE testing is not indicated on the ferritin alone
Treat the metabolic risk and recheck; MRI liver iron only if it stays high with no cause
Guideline thresholds for suspecting haemochromatosis
| BSH 2018 | EASL 2022 | |
|---|---|---|
| Ferritin, men | Above 300 µg/L | Above 300 µg/L |
| Ferritin, women | Above 200 µg/L | Above 200 µg/L |
| Transferrin saturation, men | Above 50% | Above 50% |
| Transferrin saturation, women | Above 40% | Above 45% |
| Ferritin that triggers liver assessment | Above 1000 µg/L: fibrosis assessment | Above 1000 µg/L: biopsy considered |
Most high ferritins are not iron overload
Ferritin is the body’s iron-storage protein, and a low one reliably means iron deficiency. A high one is much less specific. Ferritin is an acute-phase protein that rises with infection and inflammation, leaks from damaged liver cells and is made in excess in alcohol excess, metabolic syndrome and many cancers. The British Society for Haematology’s 2018 guideline notes that raised ferritins are found frequently in hospital practice, where they “often occur in the context of alcohol abuse, established liver disease, malignant disease, renal dialysis, inflammatory disease” and transfusion. The commonest outcome of investigating a raised ferritin is therefore finding one of those — not haemochromatosis.
The transferrin saturation separates the two. In iron overload from HFE haemochromatosis, iron absorption outruns transferrin’s capacity, so the saturation rises first and the ferritin follows. Both the BSH and the 2022 EASL guideline therefore test for HFE when the ferritin and the saturation are both raised. They agree on ferritin (above 300 µg/L in men, 200 µg/L in women) and on men’s saturation (above 50%), but not on women’s: above 40% for the BSH and above 45% for EASL. The site’s transferrin saturation calculator flags above 45%, the ACG figure for both sexes. Both guidelines treat a ferritin above 1000 µg/L as the point to assess the liver for fibrosis.
Very high ferritin is a different question. Values in the thousands and tens of thousands are seen in haemophagocytic lymphohistiocytosis (HLH), adult-onset Still’s disease, acute liver necrosis and overwhelming infection. A ferritin of 500 µg/L or more is one of the HLH-2004 criteria, and in children a ferritin above 10,000 µg/L is strongly suggestive, but in adults such values have many causes. Use the ferritin unit converter for units, and the liver iron concentration interpreter when MRI liver iron has been measured. This page supports, and does not replace, clinical judgement.
Frequently asked questions
What is the most common cause of a high ferritin?
Not iron overload. Inflammation, alcohol, liver disease, metabolic syndrome with fatty liver, malignancy and kidney disease cause most raised ferritins. A normal transferrin saturation points to one of these.
When should I test for haemochromatosis?
When both ferritin and transferrin saturation are raised: ferritin above 300 µg/L in men or 200 µg/L in women, with a saturation above 50% in men, or above 40% (BSH) or 45% (EASL) in women.
What ferritin level is dangerous?
In haemochromatosis, a ferritin above 1000 µg/L is when the liver should be assessed for fibrosis or cirrhosis. Separately, very high ferritin in an acutely ill, febrile patient with low blood counts should raise HLH, a medical emergency.
Does a fasting sample matter for transferrin saturation?
The BSH accepts a random sample: a raised random saturation may fall when repeated fasting, but fasting does not improve its predictive value. Repeat a single raised value before acting on it.
Related calculators
References
- Fitzsimons EJ, Cullis JO, Thomas DW, Tsochatzis E, Griffiths WJH; British Society for Haematology. Diagnosis and therapy of genetic haemochromatosis (review and 2017 update). Br J Haematol. 2018;181(3):293–303.
- European Association for the Study of the Liver. EASL clinical practice guidelines on haemochromatosis. J Hepatol. 2022;77(2):479–502. Thresholds as summarised in Medscape’s hemochromatosis guidelines summary and in the J Clin Exp Hepatol guideline review (the guideline’s own page could not be retrieved for this page).
- Kowdley KV, Brown KE, Ahn J, Sundaram V. ACG clinical guideline: hereditary hemochromatosis. Am J Gastroenterol. 2019;114(8):1202–1218.
- Henter JI, Horne A, Aricó M, et al. HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2007;48(2):124–131.
- Allen CE, Yu X, Kozinetz CA, McClain KL. Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis. Pediatr Blood Cancer. 2008;50(6):1227–1235.
- Schram AM, Campigotto F, Mullally A, et al. Marked hyperferritinemia does not predict for HLH in the adult population. Blood. 2015;125(10):1548–1552.
Not medical advice. For healthcare professionals and education. Reference intervals vary by laboratory and assay — always use your own laboratory's. Never base a dose or a treatment decision on this page alone. Full disclaimer at calcengines.com/disclaimer/