Raised ferritin: what to do with six hundred

Clinical Rounds, the GPAtlas podcast. Haematology. 19 minutes. Published 31 August 2026. Free to listen.

Clinical source: our own Ocean article "Haemochromatosis", last reviewed 1 January 2026.

Transcript

Sarah: Hello, and welcome to GPAtlas Clinical Rounds. I'm Sarah, and this is the podcast where we take one thing you'll genuinely see this week and work out what to do with it.

Ben: And I'm Ben. Today, a number that lands in your inbox most weeks and has no symptoms attached to it: a raised ferritin.

Sarah: So this one doesn't start with a patient in the room, it starts with a result on a screen. Mr Bianchi is fifty-one. I saw him three weeks ago because he was tired, and I did the tiredness screen, the one we all do. And his ferritin has come back at six hundred and twenty. Everything else is normal. He feels the same as he did. And now I have to decide what that number means before I ring him, because what I say next determines whether he spends the weekend reading about liver cancer.

Ben: Three things. The one extra test that tells you whether this number matters at all. What else raises a ferritin, which is most of general practice. And what to do with it if it is iron overload, including the parts that are genuinely ours rather than the specialist's.

Sarah: So the mistake first, because it's the one our article names. Treating any raised ferritin as haemochromatosis. That's the reflex, isn't it. High ferritin, iron, haemochromatosis, order the genetics. And it's wrong most of the time.

Ben: Because ferritin on its own is a poor test for iron overload. Our article describes it as reflecting total iron stores, but also being an acute-phase reactant, raised by inflammation, alcohol, metabolic or fatty liver disease and malignancy. So a raised ferritin is a common finding with a long list of ordinary causes, and iron overload is only one of them.

Sarah: And the test that sorts it is the transferrin saturation, fasting. Our article's line is the one to build your practice on: a normal fasting transferrin saturation essentially excludes iron overload even when ferritin is high. Even when it's high. So if his saturation is normal, the six hundred and twenty is telling me about something else entirely.

Ben: And it tells you where to look next, which is the useful part. A high ferritin with a normal saturation should send you looking for inflammation, alcohol, metabolic or fatty liver disease, or malignancy. Not for genetics. That's a completely different set of questions, and most of them are answerable in primary care.

Sarah: A normal saturation excludes overload. However high the ferritin is.

Sarah: So the first-line tests are the fasting transferrin saturation and the serum ferritin, together. And it's worth knowing what the saturation actually is, because the lab report can be confusing: it's the percentage of transferrin carrying iron, calculated as serum iron divided by total iron-binding capacity, times a hundred.

Ben: And pair the ferritin with a CRP, because that flags inflammation as the reason for a high ferritin. A raised ferritin with a raised CRP in someone who's just had a chest infection is a different result to the same ferritin with a normal CRP, and the CRP costs nothing.

Sarah: And practically, that's a repeat blood test with three things on it: fasting transferrin saturation, ferritin, CRP. Which is a much better phone call than the one where you order genetics, because now you're saying we need one more blood test to work out what this means, rather than we need to test you for a genetic condition.

Ben: Saturation, ferritin, CRP. Fasting. That is the whole first step.

Sarah: Now the number that changes the urgency, and this is the one to remember from the whole episode if you remember nothing else. A ferritin above a thousand signals a high risk of cirrhosis and warrants urgent specialist referral. So six hundred and twenty is a work-it- out number. Above a thousand is a pick-up-the-phone number, regardless of the rest.

Ben: And it's worth pausing on why, because it changes how you speak to the patient. That threshold isn't about the iron, it's about what the iron has already done. Above a thousand you're no longer asking whether they have iron overload, you're asking whether they have liver damage from it.

Sarah: Above a thousand is a phone call, not a plan.

Sarah: So who should this even cross your mind for? Our article's list is more useful than the textbook picture, because it's mostly ordinary presentations. Persistent unexplained fatigue, the tired all the time consultation. Joint pain, and classically the second and third knuckle joints. Erectile dysfunction or loss of libido. Amenorrhoea. Unexplained raised liver enzymes. An incidentally raised ferritin. And any first-degree relative of a confirmed case.

Ben: And the knuckle detail is genuinely useful, because it's specific enough to ask about. Pain in the second and third metacarpophalangeal joints, so the index and middle finger knuckles, in a middle-aged person with fatigue, is a combination worth noticing. Most joint pain isn't this. But that particular pattern is a prompt.

Sarah: And the thing you cannot rely on is your hands. Our article says examination is often normal in early disease and never excludes the diagnosis, and that the blood tests do that. So the bronzed skin and the big liver from the textbook are late findings, and by then you've missed the point of finding it early.

Ben: Tired, plus the index and middle knuckles. That is the pattern.

Sarah: So say his saturation comes back high and it is genuine iron overload. What's ours and what isn't? The confirmatory genetic testing is arranged through the national pathway, and there's a consent point our article makes that I think is easy to skip: informed consent is needed because of the implications for relatives. You're not just testing him. You're testing his brother and his daughter by proxy.

Ben: And a fact worth having before you take that consent, because it changes the conversation completely. Penetrance is low. Roughly one in a hundred and fifty to two hundred people of northern European descent carry the main genotype, but only about one in five men and one in ten women with it ever develop organ damage. So a positive genetic result is not a diagnosis of disease. It's a risk.

Sarah: Which matters enormously for how you break it, because the word genetic does a lot of frightening work on its own. And it matters for his family, because his relatives are going to be offered testing, and they need to hear that number before they decide, not afterwards.

Ben: And one reassurance our article offers that patients ask about almost immediately: a predictive genetic test for haemochromatosis generally does not need to be disclosed for, or count against, most insurance, under the UK Code on Genetic Testing and Insurance. That's the fear that stops people getting tested, and it has a straightforward answer.

Sarah: A positive gene is a risk, not a disease. One in five men.

Sarah: And then the part that is genuinely ongoing primary care, which is the bit I'd underplayed before reading this properly. The confirmed patient with normal iron studies who is asymptomatic gets an annual ferritin and transferrin saturation, and you can consider blood donation. That's a recall on your system, not a hospital appointment.

Ben: And the donation route is neater than people realise. NHS Blood and Transplant accepts otherwise eligible patients aged seventeen to sixty-five with haemochromatosis and a ferritin below five hundred, who can then donate as often as every six to twelve weeks. So maintenance treatment, for a lot of these patients, is giving blood. Which is a much better thing to tell somebody than a lifelong hospital appointment.

Sarah: And two things to actively look for at that annual review. Screen for and treat diabetes, and stay alert to cardiomyopathy. Those are the complications that arrive quietly, and they're both ours to spot.

Ben: With one caution about the haemoglobin, which is counter-intuitive. You'd expect anaemia as kidney or liver disease progresses and you should check for it, but this condition can preserve or even raise the haemoglobin. So a normal Hb here isn't the reassurance it usually is.

Sarah: Annual ferritin and saturation. And blood donation counts as treatment.

Sarah: Two pieces of practical advice that patients never expect and that come straight from us. The first is food safety: avoid raw or undercooked shellfish and seafood, because iron overload predisposes to severe Vibrio infection, and also Listeria and Yersinia. That's a concrete, memorable instruction and nobody else will give it to him.

Ben: And the second is an expectation to set early rather than late. Joint symptoms often persist despite normalised iron. So if his knuckles hurt, treating the iron may not fix them, and telling him that at the start is much kinder than letting him discover it after a year of venesection and conclude the treatment failed.

Sarah: No raw shellfish. And the joints may not improve.

Sarah: So back to Mr Bianchi and the phone call. What I actually say is that his iron stores look high, that there are several common reasons for that and iron overload is only one of them, and that one more fasting blood test will tell us which. That's honest, it's short, and it doesn't put the word genetic into his weekend.

Ben: And if the saturation is normal, which statistically it usually will be, the work isn't finished, it's redirected. Inflammation, alcohol, fatty liver, and the malignancy question. That's a proper primary care assessment, and it's a more likely route to something that matters for him than the genetics would have been.

Sarah: Usually the saturation is normal. Then the real work starts.

Sarah: Let me widen this out, because a raised ferritin is really a worked example of something more general, which is what to do with an abnormal number on a screening panel you ordered for a different reason.

Sarah: I ordered Mr Bianchi's bloods because he was tired. I wasn't asking about his iron. And now I've got a number that's abnormal, that he has no symptoms from, and that has a frightening condition attached to it in the public imagination. That situation arises constantly, and how you handle the first phone call determines the next six weeks.

Ben: And the structural answer here is unusually clean, which is why this one is worth learning properly. There is a single second test that either closes it or opens it. A normal fasting transferrin saturation essentially excludes iron overload however high the ferritin. So you're not embarking on an investigation, you're doing one more blood test that resolves the question.

Sarah: Which is exactly what I'd say to him. There's one more test, it's fasting, and it will tell us whether this number matters. That's a complete, honest, non-frightening account of where we are, and it doesn't require me to mention iron overload, genetics or the liver at all yet.

Ben: And if the saturation is normal, the ferritin still needs explaining, but the list is ordinary primary care: inflammation, alcohol, metabolic or fatty liver disease, malignancy. Pairing it with a CRP at the same time often answers it in one go. And a raised ferritin that turns out to be fatty liver is not a wasted investigation, it's a cardiometabolic finding you'd want anyway.

Sarah: One fasting test either closes it or opens it. That is the whole message.

Ben: And a note on who else to think about once it is confirmed, because this is a condition where the diagnosis extends beyond the patient. Cascade screening covers first-degree relatives, so parents, siblings and adult children, offered genotyping and iron studies after genetic counselling.

Ben: With one condition attached that determines whether it applies at all: the index case must be a C282Y homozygote for cascade testing to apply. So it isn't every raised ferritin in a family, and it isn't every genetic variant. That's a specific criterion, and knowing it stops you promising a family something the pathway won't deliver.

Sarah: The family question depends entirely on the index case's genotype.

Sarah: And the reason I wanted to do this one as an episode is that it isn't really about haemochromatosis. It's about the fact that we order broad blood panels for vague symptoms many times a day, and every one of those panels can return a number like this.

Sarah: The discipline that matters is knowing, before you ring, which single second test would settle it. For a raised ferritin that's a fasting transferrin saturation. Having that in mind changes the phone call from a worrying announcement into a next step, and it stops the reflex of ordering the frightening test first.

Ben: Know the one test that settles it before you make the call.

Ben: Exam corner. A fifty-one year old man is investigated for fatigue. His ferritin is six hundred and twenty. Liver enzymes, full blood count and renal function are normal, and he drinks around ten units a week. What is the most appropriate next step? A, request HFE genotyping. B, request a fasting transferrin saturation and CRP. C, refer urgently to hepatology. Or D, repeat the ferritin in three months.

Ben: It's B. Ferritin alone cannot distinguish iron overload from the many other causes of a raised result, and a normal fasting transferrin saturation essentially excludes overload however high the ferritin is. A is the common error, because genotyping is for people who meet the biochemical criteria first. C would be right above a thousand, which signals a high risk of cirrhosis, but he is six hundred and twenty. And D delays an answer that one blood test can give you now, while leaving him to worry for three months.

Sarah: So. Three things for Monday. One. A raised ferritin is not a diagnosis, and a normal fasting transferrin saturation excludes iron overload no matter how high the ferritin is. Two. Above a thousand is the number that changes everything, because it signals a high risk of cirrhosis and needs urgent referral. And three. If it does turn out to be overload, most of what follows is yours: an annual ferritin and saturation, diabetes screening, and blood donation as maintenance.

Sarah: One thing to reflect on, if you're logging this. Think about the last raised ferritin you saw. Did you order a transferrin saturation, or did you order the genetics? The full transcript and the references are on the episode page. Ben and I are synthetic voices. The medicine isn't. See you next week.

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