The video version of this podcast can be found here: ·      https://youtu.be/qNboajtlrrsThis channel may make reference to guidelines produced by the British Society for Haematology. The content on this channel reflects my professional interpretation/summary of the guidance and I am in no way affiliated with, employed by or funded/sponsored by them.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.   Intro / outro music: Track: Halfway Through — Broke In Summer [Audio Library Release] Music provided by Audio Library Plus Watch: https://youtu.be/aBGk6aJM3IU Free Download / Stream: https://alplus.io/halfway-through  There is a podcast version of this and other videos that you can access here: Primary Care guidelines podcast:  ·      Redcircle: https://redcircle.com/shows/primary-care-guidelines·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK·      Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148 There is a YouTube version of this and other videos that you can access here: The Practical GP YouTube Channel: https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk 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.15166The link for the British Society for Haematology website can be found here·      https://b-s-h.org.uk/Disclaimer:The Video Content on this channel is for educational purposes and not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on this YouTube channel. The statements made throughout this video are not to be used or relied on to diagnose, treat, cure or prevent health conditions. In addition, transmission of this Content is not intended to create, and receipt by you does not constitute, a physician-patient relationship with Dr Fernando Florido, his employees, agents, independent contractors, or anyone acting on behalf of Dr Fernando Florido.TranscriptIf you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.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 deficiencyRight, 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 episodeA 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 TsatThen 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 an elevated serum ferritin including hemochromatosis, Still disease, and other rare disorders How do we investigate raised serum ferritin?When ferritin is raised, the most crucial questions to ask are (i)            is it secondary to a known clinical condition, and (ii)          (ii) is it associated with iron overload?. A clinical history and examination, together with a few simple investigations, will often reveal the probable underlying cause. In particular, patients should be questioned about alcohol intake and other risk factors for liver disease, transfusion history or oral iron supplementation, family history of iron overload and the presence or absence of diabetes mellitus, obesity and hypertension, history of early cataracts, as well as for symptoms and signs that may point to an underlying inflammatory or malignant disorder. Initial investigations should include a full blood count, repeat ferritin, Tsat, renal function tests and LFTs (with viral hepatitis serology if LFTs are abnormal) and inflammatory markers, such as CRP and ESR. Glycosylated haemoglobin levels may indicate impaired glucose tolerance, and raised serum lipids, body mass index and hypertension may point to underlying metabolic syndrome. Abdominal ultrasonography may demonstrate an echogenic liver suggesting alcohol- or non-alcohol-related fatty liver disease. Iron overload is more likely to be present if the ferritin has risen progressively or the ferritin is >1000 μg/l.It is worth noting that acute infections, menstrual bleeding and recent blood donation can temporarily reduce Tsat to within the normal range in patients with iron overload indicating that normal Tsat does not completely exclude iron overload. In the setting of persistent borderline results, genotyping for haemochromatosis should be performed.Males with ferritin > 300 μg/l and Tsat >50% and females with ferritin > 200 μg/l and Tsat > 40% will usually have iron overload. We will leave this here as we are not looking into the diagnosis or management of haemochromatosis here today.How do we manage a raised ferritin without elevated transferrin saturation?In otherwise well patients with unexplained elevated ferritin and Tsat <40% (female) or <50% (male), a period of observation may be informative: stable, moderately increased levels may not require further investigation, whereas fluctuating levels are typically seen in hepatic steatosis or alcohol excess. Persistent unexplained high levels, especially at levels >1000 μg/l, merits consideration of onward referral to a specialist, usually a hepatologist. In most cases of a high ferritin secondary to inflammatory or other conditions, management of the underlying condition will lead to reduction in ferritin levels. For example, alcohol abstinence will usually lead to improvement in ferritin within weeks to months; and weight loss and improved control of diabetes and blood pressure will usually lead to lowering of levels in patients with metabolic syndrome.There is no evidence to support venesection therapy in patients with increased ferritin associated with liver disease other than heamochromatosis In ConclusionThe finding of a raised serum ferritin is a common conundrum in modern day clinical practice, both in primary and secondary care. Iron overload is a relatively uncommon cause of this picture and can be excluded by the finding of a normal transferrin saturation, so consideration of the many reactive causes like hepatic, malignant, renal, haematological and metabolic causes is important: many cases will not require further investigation if a few simple investigations are performed. Rarer causes will require specialist molecular genetics for diagnosis.So that is it, a review of the laboratory investigations of a raised serum ferritin. We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.Thank you for listening and goodbye.

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