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My name is Fernando Florido (also known as Juan Fernando Florido Santana), a GP in the UK. In this episode, I will go through the guideline by the British Society for Haematology on the investigation and management of a raised serum ferritin, focusing on what is relevant in Primary Care only.

In the last two episodes I covered the guideline on iron deficiency and functional iron deficiency.

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.  

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The link to the guideline by the British Society for Haematology on the investigation and management of a raised serum ferritin can be found here:

·      https://doi.org/10.1111/bjh.15166

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·      https://b-s-h.org.uk/

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Transcript

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Hello and welcome, I am Fernando, a GP in the UK. Today, we will go through the guideline by the British Society for Haematology on the investigation and management of a raised serum ferritin, focusing on what is relevant in Primary Care only. A link to it is in the episode description.

If you haven’t already, I recommend that you check out the last two episodes where we covered the laboratory diagnosis of both iron deficiency and functional iron deficiency

Right, let’s jump into it.

Serum ferritin level is one of the most commonly requested investigations in both primary and secondary care. Whilst low serum ferritin levels invariably indicate reduced iron stores, raised serum ferritin levels can be due to multiple different causes, including iron overload, inflammation, liver or renal disease, malignancy, and metabolic syndrome.

Reduced ferritin levels are only found in patients with reduced body iron stores. However, in some circumstances, for example in patients with co-existent inflammatory disorders, ferritin may be within the normal or elevated range even when iron stores are reduced and anaemia is due to iron deficiency.

On the other hand, the clinical and laboratory management of patients with raised ferritin values is not that well recognised and this is why we are covering it here.

Levels in serum can be raised because of inflammation, tissue damage as well as by any condition or treatment that leads to a genuine increase in iron stores (e.g. blood transfusion or iron infusion).

Most UK path labs simply report 300–400 μg/l as the upper limit of normal for ferritin in adult males and 150–200 μg/l as the upper limit of normal for adult females. There is however considerable variation in response to age, ethnic origin and sex. Mean ferritin values in neonates are high (around 200 μg/l) and remain so for about 2 months.

Mean ferritin values are higher at all ages in adult black males. In black females, higher ferritin values are only seen after the menopause. In multi-ethnic population studies in the USA it was found that elevated ferritin values are found more frequently in Afro-Caribbean and Asian subjects than in the white or Hispanic population. Indeed, very high ferritin levels >1000 μg/l are 2–3 times more common in black and Asian volunteers despite not having a true iron overload problem so it is argued that the normal ranges should take into account the variation due to age, gender and possibly ethnic origin

Serum ferritin is the most frequently requested haematinic assay in the UK and some 50% of ferritin requests are made from primary care.

The commonest causes of a high ferritin without iron overload relate to inflammatory disorders, malignancy, chronic alcohol consumption, liver disease or metabolic abnormalities.

For the majority of persons with a raised ferritin, chronic inflammatory or infective causes as well as liver disease, alcohol and malignancies will be the more likely conditions seen in practice, and if clinically apparent, further investigations of the causes of the high ferritin may not be necessary. Let’s look at the different causes individually:

In the Liver: Elevated ferritin is seen in almost any cause of liver injury, including alcoholic and non-alcoholic steatohepatitis (NASH), and viral hepatitis

In the Kidneys: Ferritin is not a useful marker of iron stores in patients with chronic kidney disease (CKD), and is elevated in almost half of all patients on maintenance haemodialysis but the raised ferritin does not represent iron that is available for erythropoiesis. For CKD patients on treatment with erythropoietic stimulating agents (ESA), iron supplementation should routinely be offered unless their ferritin is >800 μg/l.

In Malignancy: ferritin  is frequently elevated, and cancer has been the most frequent association in some studies of the causes of a high ferritin.

In Inflammatory and infective disorders: ferritin levels may correlate with disease activity, for example in systemic lupus erythematosus (SLE) and rheumatoid arthritis. Other inflammatory conditions and acute or chronic infections will also produce elevations in ferritin, usually with elevated CRP, but normal Tsat.

Mention should be made of anaemia of chronic disease (ACD), also termed anaemia of inflammation, the pathogenesis of which includes a state of functional iron deficiency, which we discussed in the last episode

A more recently described cause of raised ferritin is the metabolic syndrome, sometimes referred to as dysmetabolic hyperferritinaemia: patients typically demonstrate elevated ferritin levels with normal Tsat

Then we have Haematological causes and: A variety of red cell disorders, characterised by ineffective erythropoiesis or haemolysis, are associated with increased ferritin; these include thalassaemic disorders, hereditary spherocytosis and inherited or acquired sideroblastic anaemias. Prolonged or chronic transfusion therapy, for example in patients with major haemoglobinopathies, myelodysplastic syndromes, or during treatment for haematological malignancies, will also cause transfusional iron overload.

So in summary, reactive causes of raised serum ferritin levels, including malignancy, inflammatory disorders, renal failure, liver disease and metabolic syndrome, are all considerably more common than true iron overload.

There are other genetic causes of