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 eg associated with acute liver inflammation. These are often associated with normal transferrin saturation, <50%. 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 till after the menopause.
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.
C.M & L.W 27-03-24
Who to refer:
- Patients with significantly raised ferritin and high transferrin saturation >50% in males, >40% in females – Please send HFE gene testing bloods prior to referral
- Patients with a genotype associated with haemochromatosis with normal LFTs:
- 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 WGH, RIE or St John’s, if no evidence of reactive causes.
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.
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.
