e-learning | Investigating patients with a raised ferritin

This is a guideline from the BSH on investigating and managing a raised ferritin. It was published in 2018. I'm going to summarise it, but there is a lot more in the guideline, which would be useful to refer to if you have a puzzling patient.

Background

In healthy people, the ferritin level is directly proportional to the body's iron stores. Ferritin is a protein in the blood that contains iron. Ferritin is not a very good marker of iron stores in people with severe CKD.

Transferrin saturation. Transferrin carries iron around the body. If there isn't enough iron, transferrin saturation will be low. Too much iron and transferrin saturation will be high. Ideally it should be done on a fasting sample, but mostly it isn't. If you have a borderline result, it may be worth repeating on a fasting sample. It is worth noting that acute infections, menstrual bleeding and recent blood donation can all reduce transferrin saturation. This may mask an iron overload condition.

What normal variations are there in ferritin levels?

I was not aware of any of the following, so thought it worth noting.

  • Men have higher levels on average than women.
  • Women have lower levels while menstruating, then after menopause, their levels go up.
  • Black adult males have higher levels than white males at all ages.
  • Black adult females have higher levels than white females only after menopause.
  • It is more common to find very high levels of ferritin in people of Afro-Caribbean or Asian descent than it is in people of White or Hispanic descent. However it is rare to find haemochromatosis in people of Afro-Caribbean or Asian descent.

What are the causes of raised ferritin?

The list is quite long and includes lots of rare diseases. It is worth noting that in primary care, the diagnosis is not normally going to be haemochromatosis.

In general the causes can be split into 3 groups:

  • Increased ferritin synthesis due to iron accumulation. This includes haemochromatosis, thalassaemia, some myelodysplastic diseases and secondary overload eg after transfusion.
  • Increased ferritin synthesis not due to iron accumulation. This includes malignancies, infections, chronic inflammatory disorders and autoimmune disorders.
  • Increased ferritin due to cellular damage. This includes liver disease (eg non-alcoholic fatty liver disease - NAFLD or chronic hepatitis) and chronic alcohol excess.

The most common causes in primary care are:

  • Chronic inflammatory disorders
  • Infective causes
  • Liver disease
  • Malignancies (eg hepatocellular carcinoma, breast, pancreatic and haematological malignancies).
  • Metabolic syndrome.

What other tests should we do if we find a raised ferritin?

  • LFT
  • FBC and film
  • Hepatitis viral serology (if LFT are abnormal)
  • Abdo USS (consider this if the raised ferritin is unexplained or LFT are abnormal).
  • UE
  • ESR / CRP
  • Transferrin saturation
  • HbA1c / Lipid profile (consider if metabolic syndrome is likely).

What should we do with all these results?

There is a very useful flow chart in the guideline. I have added this below:

It is useful to note that they advise that in a well patient, with normal transferrin saturation and a stably raised ferritin of < 1000 micrograms/L, it is OK to watch and wait for 3-6m. In that time, lifestyle interventions should be tried. These should include reducing alcohol, losing weight, better diabetes control and better hypertension control. These should reduce the ferritin in weeks or months if they are the culprit.

Alcohol excess and fatty liver will often cause a fluctuating raised level of ferritin.

If the raised level is unexplained, persistent or > 1000 micrograms / L, then patients need referring to hepatology.

When should we be worrying about haemochromatosis?

This guideline advises that the following features make a diagnosis of haemochromatosis more likely:

  • Ferritin has risen progressively.
  • Ferritin is > 1000 micrograms / L.
  • LFT may be abnormal.
  • Transferrin saturation will be raised.

However, any patient with a raised ferritin, normal FBC and raised transferrin saturation should be referred to hepatology.

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