High Ferritin

Definition

Increase in ferritin concentration >300ug/l for men and postmenopausal women or >200 ug/l for premenopausal women.

Ferritin levels may be increased as an acute phase reactant for example associated with acute liver inflammation. These are often associated with normal transferrin saturations (<50% on a fasted sample). High ferritin will also be expected in patients with repeated transfusions, but such patients will usually be under Haematology review.

If transferrin saturation >50% in males or > 40% in females, or there is a family history of haemochromatosis, consider testing for haemochromatosis. Females with haemochromatosis often do not manifest high ferritin until after the menopause.

Please note: Patients with confirmed Haemochromatosis should be referred to Gastroenterology at BGH, not to Haematology

Haemochromatosis Gene Screening.

Hereditary Haemochromatosis – RefHelp (nhslothian.scot)

Haemochromatosis gene screening is done on a red EDTA sample sent to Haematology Laboratory who will then forward on to Molecular Genetics in Dundee for testing.

The various outcomes of testing are:

C282Y Homozygotes This genotype is associated with highest risk of iron overload and patients should be referred for assessment and monitoring by Haematology.
Compound heterozygotes (C282Y/H63D) This genotype may be associated with iron overload but other causes of elevated ferritin eg alcohol excess or metabolic syndrome should be sought if iron overload present. Please refer.

H63D homozygotes This genotype is not usually associated with iron overload. Other causes of elevated ferritin eg alcohol excess or metabolic syndrome should be sought if iron overload present.
Single gene carriers (H63D or C282Y)This genotype is not associated with iron overload.
Non–carriers This patient does not carry either of the mutations commonly associated with hereditary haemochromatosis.

Who to refer, who not to refer, how to refer

Who to refer:

Patients with significantly raised ferritin and high transferrin saturation >50% in males, >40% in females – Please send HFE gene testing bloods in first instance
Patients with a genotype associated with haemochromatosis should be referred to Gastroenterology

Homozygous for C282Y or H63D
Compound heterozygotes for C282Y/H63D

Patients with very high ferritin (>1000 ug/l) which is unexplained

Who not to refer:

Please refer to GI / Hepatology:

patients with suspected and/or confirmed haemochromatosis and abnormal LFTs and patients with ferritin > 1000 ug/L.

Patients with clear cause for elevated ferritin eg chronic inflammatory or infective illness, transfusion dependent patient, patient with liver disease including NAFLD/ALD. Refer to the appropriate specialty if concerning features.

How to refer:

SCI Gateway to Department of Haematology if no evidence of reactive causes as described above

Primary care management

Primary care investigations

(Which help assess for underlying causes e.g. inflammatory conditions, liver disease, malignancy which could cause a reactive rise in ferritin.)

FBC + film
Biochemistry including renal function, liver function, iron and transferrin, LDH calcium, albumin, urate
Inflammatory markers – CRP
Haemochromatosis (HFE) gene screening if transferrin saturation >50% in males or >40% in females.

Resources and links

BSH Guideline: Diagnosis and therapy of genetic haemochromatosis (Review and 2017 update) https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjh.15164

Fitzsimons et al (2018) Investigation and management of raised ferritin https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.15166.

Last reviewed: 17/01/2025

Next review date: 17/01/2027

Author(s): Charlotte Robertson.