Seminar : Living with genetic haemochromatosis with Dr Ted Fitzsimmons

[00:00:00] Neil McClements (CEO, Haemochromatosis UK): [00:00:00] Hello everybody. Welcome to our first event, celebrating and marking world hemochromatosis week.For those of you don't know, my name is Neil McClements. I'm the chief executive of hemochromatosis UK, and I'm absolutely delighted and thrilled to be able to introduce Dr. Ted Fitzsimmons to you today.

[00:00:27] Ted has been a very longstanding friend of the charity over many, many years. And for those of you who don't know him is a consultant hematologist based in Glasgow and has had a particular interest in genetic hemochromatosis going back very very many years. And may recall the name Fitzsimmons, Ted was one of the lead authors of the British society of hematology guidelines, which were published a couple of years ago, which are really the, sort of the best practice guidelines, for NHS clinicians to [00:01:00] follow when diagnosing and treating people with genetic hemochromatosis and iron overload.

[00:01:06] So without further ado, I'm now going to hand over to Ted.

[00:01:15] Dr Ted Fitzsimons (Consultant Haematologist): [00:01:15] Thank you.So can I give everyone a warm welcome, a virtual welcome to Glasgow and this rather pleasant Tuesday afternoon. So I'm Ted Fitzsimmons. I'm a consultant hematologist here in west Glasgow. And just before we start, I'm delighted to be doing this webinar. And my thanks to Neil and to hemochromatosis UK, for making this altogether possible.

[00:01:49] So that's us we're living with genetic hemochromatosis. Okay. And as everyone in this webinar knows, this is world hemochromatosis week. [00:02:00] But as we know outside of this meeting, most people would greet this news with world what week, but we know differently. While, the rest of the world looks on iron as being a very positive thing and the sort of beneficial effects of iron.

[00:02:20] And as we see in the, illustrious Arnold Schwartzenegger and former, governor of California, but we are aware that iron is not altogether such a good thing to have, because we know that genetic hemochromatosis is the most common genetic abnormality to affect Northern European populations, particularly those of Anglo-Saxon and the Celtic populations.

[00:02:53] It's so common. In fact, that one in eight, one in eight of us are carriers for [00:03:00] hemochromatosis and somewhere between one and 150 and one in 200 are genetically predisposed with two copies of the abnormal gene referred to as C282Y homozygous. The interesting thing for these homozygous is that for every homozygous that we identify, we estimate that there are between eight and 10 homozygotes that are unrecognized.

[00:03:29] And that would mean in the UK somewhere between 200 and 250,000 homozygotes are undiagnosed. So it's not uncommon that we'd refer to hemochromatosis as the most common condition you have never heard of.

[00:03:52] So we know it's not just the Celtic curse.  [00:04:00] It's a north European problem, which as a result of immigration has taken hemochromatosis to be a worldwide condition. And there are now active hemochromatosis units in Canada, Australia, and elsewhere throughout the world.

[00:04:15] So perhaps it's no longer appropriate for us to refer to genetic hemochromatosis as the Celtic curse.

[00:04:27] Why do we need iron? Well, we need an iron actually for these chaps. And these are our red blood cells and red blood cells are small packets of hemoglobin. And the heme in the hemoglobin has central iron molecule as an essential component of heme. And it's that iron in heme that allows hemoglobin to pick up oxygen in the lungs and deliver oxygen to the tissues.

[00:04:57] So iron is [00:05:00] extremely important for our blood and for our oxygenation of tissues. And I'm a hematologist. I spend a lot of time looking at blood films and here are normal red cells, red cells that are full of this red hemoglobin, this oxygen carrying molecule. And here we have. Red cells in the state of iron deficiency, they are pale and they are small and they are less able to carry oxygen.

[00:05:34] So there are plenty of good things about iron. And as a hematologist, I know that most of the iron we need, goes to our red cells,

[00:05:50] But it's not just red cells that need iron. Every cell needs iron our liver cells need iron there are essential [00:06:00] enzymes in our liver. Some of, many of which are iron containing and body metabolism cannot function without liver being provided with iron. Our muscles need iron as the hemoglobin in our red cells requires iron.

[00:06:17] So to do this, there's a myoglobin in our muscles. Pancreas needs iron, our pancreas, producing insulin, our heart, our heart muscles need iron. Even our nails need iron. If you're short of iron, your nails will take an abnormal shape and become brittle. So from a very early stage, in my medical training, I was aware of the importance of iron.

[00:06:46] And in 1980, I set off to study hematology in Carters at Cardiff was really the center of the study of iron metabolism. At that [00:07:00] time.

[00:07:03] Now there were other things that Cardiff had during my time in Cardiff and in actual fact in 1982 and 1984, the Scottish rugby team won in Cardiff for the first time. And that's me as a young bloke in 82, with my young wife who we arrived in Cardiff, actually straight from honeymoon. And if any of you are treated for hemoglobin were treated for hemochromatosis in fife, you might recognize this chap poking his head through between the two other heads.

[00:07:35] This is Dr. John McCallum who trained in hematology, with me in Cardiff, but as far as I was concerned, the best thing about Cardiff was the great, Alan Jacobs.Alan Jacobs was the leader of the three wise men of iron. Now when I joined Cardiff, I was certainly not a wise man, [00:08:00] I was definitely just one of the shepherds, but the three were Alan Jacobs,

[00:08:04] Professor Mark Worwood and Ivor Cavill, Alan Jenkins is dead, but Mark Warwick continues to support hemochromatosis. And who remains still active today with his interest in iron. And this group developed the serum ferritin assay, and from the, all the work that they did, they could calculate that for one unit of ferritin and serum that was equivalent to approximately five to eight milligrams of body iron of iron in our body stores.

[00:08:40] Now, they also developed a technique called Ferrokinetics and Ferrokinetics gave us an even better picture of iron metabolism. Now we knew that we only required one to two milligrams of dietary iron a day to remain an iron balance. But with Ferro [00:09:00] kinetics, they discovered that we required to transfer something like 30 milligrams of iron through our plasma everyday to feed all the cells in our body.

[00:09:12] And of course, all cells need iron. So if we are absorbing only one or two milligrams of iron a day where does this 30 milligrams of iron come from?

[00:09:27] So before we start to discuss iron metabolism, I just want to run briefly through a few terms just to make everyone comfortable with the diagrams when we come to them. So transferrin, transferrin is the protein that transports iron through the blood to our cells. The laboratory frequently measures transferrin and expresses the result in relation to the amount of iron that the transferrin is carrying.

[00:09:59]And we refer to that as the transferrin saturation [00:10:00]. If 30% of transferrin has got iron on it, then the transferrin is 30% saturated. If the transferrin is full of iron and it is 100% saturated.

[00:10:18] Ferritin. We are all familiar with the term ferritin, ferritin is a protein that stores excess iron and stores it safely within cells, ferratin is predominantly an intracellular protein to store iron safely. There is a tiny amount of ferritin that’s found in serum, but that ferritin and serum doesn't contain any iron.

[00:10:46] And in fact, doesn't contribute to iron metabolism at all.

[00:10:53] Where serum ferritin is particularly valuable, is that the level of ferritin that we can find in the serum [00:11:00] is directly related  to the amount of iron that we hold in our bodies. And roughly speaking, one unit of fatten is equivalent to something like five to eight milligrams of iron in our body stores. And the other term that I'm going to use is the word hepcidin and hepciden is best remembered as being low iron hormone.

[00:11:30] So let's look a little bit at transferrin in more detail. This Y shaped diagram indicates a general picture of what transferrin looks like and transferrin has two binding sites that contain iron and the little red dots here represent iron, the yellow Ys transferrin. And then in the normal situation about 30% of transparent is [00:12:00] saturated with iron.

[00:12:06]In iron deficiency the liver recognizes that the body is short of iron and it makes more transferrin to try and catch what little iron there is about. So you'll see the iron level is reduced, but the transferrin production is increased,so the saturation reduces.In iron deficiency, transferrin saturation is usually less than 15%.

[00:12:36]In haemochromatosis the liver senses that we've got plenty of iron and in an effort to try and protect the body. The liver produces less transferrin to grab so there's not less in an attempt to grab less iron, but in actual fact that the liver is doing us no favors at all here because [00:13:00] the reduced levels of transferrin become fully saturated with iron and some iron escapes from transferrin.

[00:13:09] And we call that non-transferrin unbound iron, and this is iron that is highly toxic. And the more that transferrin is saturated with iron, the more likely we are to find non-transferrin iron and non-transferrin bound iron is a highly unstable material causing lipid peroxidation and all sorts of tissue damage.

[00:13:41] The other term we're all familiar with the serum ferritin and serum ferritin is a good measure of body iron stores. It's reduced an iron deficiency anemia, and it's increased in iron overload. And in genetic hemochromatosis. The problem here is that we call serum [00:14:00] ferritin and acute phase protein.

[00:14:02] So it's elevated in a lot of other conditions, unrelated to iron. So if there is tissue inflammation or tissue damage serum ferritin levels will rise. If the patient has liver disease serum ferritin will rise. And if the patient is drinking too much alcohol ,serum ferritin will rise. So the problems of  serum ferritin is a great measure.

[00:14:26] A very helpful measure in the study of hemochromatosis. The problem is that it is not just influenced by iron levels, but it's influenced by a whole load of other things. Going on at the same time.

[00:14:44] So let's look at iron homeostasis in a little bit more detail. So normal situation, the body contains something like four grams of iron, but we absorb only one to two milligrams of iron per day to stay in iron balance [00:15:00] . And that's because there is no way that the body can excrete nor increase amounts of iron.

[00:15:07] And the amount of iron that gets into our blood to bind to transferrin is regulated by the hormone hepcidin and hepcidin, our diet or Western diet contains something like 15 to 20 milligrams of iron. But through the influence of hepcidin, we absorb only maybe one or two milligrams of iron per day.

[00:15:30] And that deals with these small amounts of iron that we lose in the bowl everday.

[00:15:37] Iron is transfered to transferrin and the transferrin then takes the iron to our bone marrow, to our muscles, to our livers, to our heart, to our pancreas. The red cells last for 120 days and after the red cells die, they are eaten by [00:16:00] our storage cells and the iron is released into our body stores and hepcidin then controls the release of iron from our body stores to transferrin.

[00:16:14] Now, in the course of a day 30 milligrams of iron will pass through our plasma, one or two of those milligrams come from our diet. The vast majority come from our stores.  And both iron released from out stores and iron absorbed from our diet are controlled by the hormone hepcidin.

[00:16:44] Putting simply, looking at it simply, in the normal situation. We've got four grams of iron. Three of our grams is in our red cells, one gram is in other tissues. And one milligram is what we require every day [00:17:00] to stay in iron balance.

[00:17:05] Genetic hemochromatosis is a very difficult condition to diagnose, trying to diagnose it on clinical grounds is very difficult. Sometimes near impossible. It's a condition where the symptoms come on gradually, they come on over many years. The body changes happen slowly, happen over many years. So clinical diagnosis is extremely difficult to diagnose hemochromatosis.

[00:17:34] we have to rely on laboratory features and the classic laboratory features of hemochromatosis is that the ferritin level and serum is raised. The amount of iron and transferrin is increased. The transferrin saturations increase and from the work done in 1996 by Feder. We know that the vast majority of [00:18:00] patients with hemochromatosis, now, we now know, they have this abnormal HFE gene, which we describe as being the abnormality described on the DNA is described the C282Y.

[00:18:14] And because the affected person has two doses of this abnormal gene we refer to it as being homozygous. So there are two doses of the abnormal gene in most patients, in the vast majority of patients with genetic hemochromatosis. And the result of this genetic abnormality is that the patient produces low levels of hepcidin, low levels of the low iron hormone.

[00:18:43] So let's look at iron metabolism, in hemochromatosis, and let's consider a fairly bad case. This badly affected patient has lost hepcidin. They have the HFE two gene abnormality they’re C282Y homozygous. [00:19:00] They've lost hepcidin so the increase the amount they they'll continue to lose one or two milligrams of iron per day in the bowel, but with a loss of hepcidin they’ll absorb

[00:19:13] maybe an extra three or four milligrams of iron per day. And that will go into the, into the, into the blood. It will bind to transferrin and it will be carried to the bone marrow to meet red cells, to the muscles, to the enzymes in the liver, to the heart, to the pancreas, the red cells will last 120 days going to the stores.

[00:19:37] And eventually the stores will start to increase the amount of iron. It's been drip fed an extra three or four milligrams a day, an extra three milligrams of iron per day. That's approximately equal to a gram of excess iron a year, a thousand milligrams, and this excess of iron gradually build up in our body [00:20:00] stores and our body stores

[00:20:03] the release of iron is the once again, control by hepcidin and our body stores will then allow excess of iron to escape from our stores into our plasma. Transferrin will become fully saturated. And as much as 50 milligrams of iron will pass through the body each day, now we only need 30 milligrams of iron to feed our red cells.

[00:20:29] So 20 milligrams of iron are now going elsewhere, they're going to our muscles. They're going to our liver. They're going to our pancreas, go to our skin. This is what happens in a badly, badly affected patient with genetic hemochromatosis. So look at it simply in this, in this bad situation, the patient's got excess 20 grams of iron.

[00:20:55] The red cells only need three gams, so they're fine and they can control them. And [00:21:00] they've got a very elaborate system for controlling the amount of iron that they take up. The rest of the body cells don't have that same elaborate mechanism. So the rest of the excess tissue, the excess iron goes to our tissues.

[00:21:13] And it leads to ferritin being grossly elevated and transferrin being fully saturated with iron, with some iron, perhaps not even being bound to transferrin and being metabolically, this fairly active non-transferrin bound iron.Now this is a summary slide that puts both pictures together from our guidelines in the British journal of hematology.

[00:21:38] And they may on the face of it appear confusing. But I like to think of it simply as there are two gates that allow iron into our blood. One of these gates is the gut that controls our iron absorption and the other iron gate is iron from our [00:22:00] body stores, which allows iron into our plasma. Normally in the gut we only absorb one or two milligrams of iron per day, 28 to 30 milligrams will come from our stores, but these are the two gates.

[00:22:16] There’s a gate controlling iron from the gut and a gate controlling iron from body stores. And this gate, these gates are opened and closed by hepcidin and hemochromatosis. They loose hepcidin, we see more iron absorbed from the gut than is lost. What we see considerably more iron released from our stores, so that transferrin becomes saturated and 50 milligrams rather than 20 to 40 milligrams of iron will pass through the body each day.

[00:22:50] And that iron only three grams will get to the red cells. So the rest of the iron go to the liver where it causes damage, pancreas [00:23:00] where it causes damage to the joints which casues arthiritis. To the heart, to the heart but it causes tissue damage as well. So let's just look at what happens.

[00:23:11] We've got 20 grams of iron. And where does it go to these other tissues? Well, it goes to the liver and iron excess in the liver will cause liver damage, ultimately leading to cirrhosis and risks of liver cancer. Iron going to the pancreas. The pancreas is the source of the hormone insulin, lose insulin and you develop diabetes.

[00:23:37] Iron going in excess to the joints causes, hemochromatosis arthritis. And iron going in excess to the skin can cause a particular bronzing effect and the combination of the bronzing effect in the skin and the diabetes from iron in the pancreas used to lead to the genetic haemochromatosis previously being known as bronze diabetes. [00:24:00]

[00:24:09] and this is an x-ray of a patient with the arthritis of hemochromatosis and classically, you can see the abnormality here. This, this is boney sclerosis. This is arthritis in the index finger and the middle finger of the hand. And that's the classic site for hemochromatosis arthritis. We know other joints are affected.

[00:24:31] Patients with hemochromatosis are twice as likely to need hip replacements as patients who don't have it. The other joint, that's the joints that are affected are the ankle joints. But the classic joint that's affected of the knuckle joints are the index and the middle finger.

[00:24:51] This, you’ll immediately recognize as normal liver. And this is what the normal liver looks like under the microscope [00:25:00] in a patient with hemochromatosis. However, if you just put that picture into your mind, the liver architecture is grossly disturbed and what you see around here is scar tissue. This is fibrosis this is scar tissue and the architecture of the liver has been grossly disturbed.

[00:25:22] And if we stay in this liver for iron and iron is this material that stains blue, you can see the gross iron loading in this very abnormal in this very cirrhotic liver. So cirrhosis is the most serious complication of genetic hemochromatosis in the liver.

[00:25:49] So I think it's about time we stop thinking of hemochromatosis as the Celtic curse, there is another form of Celtic curse, but I'll deal with that later in this presentation. [00:26:00] It's the silent curse far better because we know now that between 150 or between one and 151 and 200 of our population are homozygous for hemochromatosis.

[00:26:18] They've got two copies of the abnormal C282Y gene. And what we don't understand is why does everyone with this abnormality not express the gene and why do some people express the gene to considerable damage? And the other people express it with minor, very little damage. So although we know the molecular abnormality behind genetic hemochromatosis, we're far away from knowing just exactly the full story.

[00:26:51] We do know, however that menn with hemochromatosis,with this genetic abnormality are affected far more than women. And we know that [00:27:00] somewhere around about 250,000 homozygotes in Scotland are unrecognized and almost quarter of a million unrecognized, in England. So perhaps it's time we stopped, we stopped thinking about it as the Celtic curse and consider it more a silent curse.

[00:27:21] So what is the problem with the diagnosis? Well, the problem is, of course we are missing most, most patients with genetic hemochromatosis are missed. We have a problem with the missing homozygotes.

[00:27:38] So what, what testing is approved to identify genetic hemochromatosis? Well, at the minute, unselected population screening is not recommended now who's to say that it's not going to change as our understanding of hemochromatosis, [00:28:00] particularly from the studies that are going on with the UK biobank deliver information that we are not, we have not really been aware of until more recently, but for the moment while there are so many homozygotes, unaffected, and so many, there is no great move towards population screening.

[00:28:23] Having said that that may in time change. What is approved at the minute, is that family screaming, once the index case is identified, it's essential that other relevant members of the family are screened. And that screening does not just include, does not just mean check the serum ferritin in their iron,the gene needs to be looked for as well.

[00:28:47] Screening is incomplete unless the gene defect is looked for because some patients, particularly women homozygous may not express a raised ferritin or [00:29:00] transferrin, but they would still carry the gene that they could transfer to children. So it's important for the gene to be tested for in screening, not just iron and transferrin.

[00:29:11] Well, we don't recommend the screening, family screening for compound heterozygous compound heterozygous represents something like 2% of the population. So screening, family screening for that would be a huge amount of work.

[00:29:27] This is an algorithm which we have generated from work that we've done in hemochromatosis, which I'm going to describe, in a minute, which I will discuss more fully as the webinar goes on. We just bypass that. Just now.

[00:29:44] So in 2011, I was becoming increasingly concerned by the fact that there were patients who were homozygous,that were not being identified. And that [00:30:00] there wasn't really a lot of general knowledge in primary care about hemochromatosis or GPS were using serum ferritin, really looking for serum ferritin to diagnose iron deficiency anemia.

[00:30:14] And there are in 2011, there were very good guidelines for how to manage patients with iron deficiency, anemia and low ferritin. But there was absolutely no management plan available for them. They have guidelines for what GPS should do about patients with high serum ferritins. Yes. They could say, well, the patient doesn't have iron deficiency anemia that's for sure.

[00:30:36] But you needed to look to see what else was going on. So, in those days I was trying to encourage my daughter to become a hematologist. And Katie Fitzsimmons then looked at serum ferritin results in primary care patients. I'd have to say it didn't have a great effect on Katie. Katie [00:31:00] didn't become a hematologist.

[00:31:00] In fact, she's an anaesthetist in Melbourne, so that's a very negative effect of this. So we looked at iron, we looked at ferritin values that were coming out of primary care, and we decided to, we've only been to look at patients with a ferritin that was definitely not iron deficient.And this is a result of the male patients from primary care.

[00:31:23] We only looked at patients over the age of 30 because hemochromatosis is fairly uncommon in patients, less than 30. And this is a complicated site, but what it shows is that almost 20% of patients in male patients in primary care over the age of 30, have a serum ferritin above the normal limit.

[00:31:47] So almost 20% of men have serum ferritin above 300.

[00:31:55] When we looked at women and what was interesting is that [00:32:00] it didn't matter what age. It didn't matter if the patient was in the 30 to 50 age group, in the 50 to 70 age group or over 70, it didn't matter. It was consistent. Almost 20% of patients would have a raised serum ferritin. When we looked at women, it was different.

[00:32:20] If you look, the serum ferritin was was very much related to age those women in the 30 to 50 age group, only 3% had the raised ferritin above 200, in 50 to 70, it was 10% more so in the 60 to 70 year olds than the 50 to 60 year olds. But over the age of 70 figures were getting like the men 17%, almost 20% of women over the age of 70, had a raised serum ferritin.

[00:32:56] What was particularly worrying about this study [00:33:00] was that we uncovered 56 patients who had a ferritin value grossly elevated more than a thousand. And when we looked through the case notes, we found that less than half of these patients have been investigated for the high ferritin. And 32 of the 56 have high ferritins over a thousand that were unexplained.

[00:33:26] So what did we take from this study? Well, serum ferritin is one of the most common tests made and provided primary care. It's one of the most common requests that we receive in the lab from our colleagues in general practice and GP’s use it predominantly to diagnose iron deficiency anemia, not to look for hemochromatosis, almost 20% of males over the age of 30 have got a high serum ferritin.

[00:33:55] And it doesn't matter if the patient 30, 40, 50, 60, [00:34:00] it’s 20% across all age groups. It women it’s a bit different. It varies between three and 17% and it is age dependent. And here we have still a situation where as where patients with grossly elevated serum, ferritins, we're not being investigated.

[00:34:18] So this then summarizes really what we’ve found from this study. And on the basis of this study, then we carried out a second study, a much more intensive study, but we looked at patient samples coming in from primary care over a period of a year. And we ruled out, we excluded anyone with a ferritin of less than a hundred.

[00:34:43] They could still be, they could be iron deficient. And we looked to everyone, every sample coming in whose ferritin was more than a hundred. We measured transferrin saturations. And if the transferrin saturation was less than 40%, we didn't do anything else. But if a [00:35:00] transferrin saturation was more than 40%, then we looked for the HFE gene abnormality.

[00:35:08] On the basis of that study, which was a huge study, a lot of patients. We were able to develop an algorithm. In these patients, we looked at liver function tests, and we didn't find any value at all. But if we identified this was in the population from primary care over the age of 30, if women had a ferritin of more than the 200, and a transferrin saturation of about 40%, then almost 20% of this population.

[00:35:37] 16.5% of the population had genetic hemochromatosis had the C282Y homozygous abnormality. In males if the ferritin was above 300 and the transferrin saturation above 50%, then 18% of these patients could be identified as having genetic haemochromatosis. And then of course, [00:36:00] having identified the patients, we carried out family screening to look for family members.

[00:36:07] And if there's two patients, don’t forget if you’ve got two patients that are carriers.If you've got partners who are carriers, they have a one in four chance of producing children with hemochromatosis. If one of the patterns is, has got genetic hemochromatosis and the other is a carrier and that risk then becomes 50%.

[00:36:32] Okay. Now this is my celebrity slide, which I'm going to discuss more fully later and maybe just a wee bit out of place here. So we'll just move on from that. But we'll return to this slide later. So looking at what was the laboratory impact of this out algorithm, well [00:37:00] about 2% of samples from women in primary care will have a ferritin of more than 200 and a transferrin saturation at 40%.

[00:37:09] One in six of these will have the genetic hemochromatosis abnormality,in males about 6% of patients have got ferritins above 300 and transferrin saturations above 50%. And these have got about one in five chance of genetic hemochromatosis. Now this is an old slide and it was a slide which I prepared when we thought that the prevalence of hemochromatosis was maybe about one in 300.

[00:37:35] We realized now, that , at that time we calculated the enrichment was some 74. But in fact, with the prevalence of about one in 101 in 150 to 200, this algorithm enriches the catch for genetic hemochromatosis, 30 to 44. And it's a simple algorithm it’s simple to test. [00:38:00] However, what did the study course highlight?

[00:38:05] Well, it highlights that for all, we can identify 20% of the group with genetic haemochromatosis. It means that 80% of patients with raised ferritins and transferrin  saturations don't have genetic hemochromatosis. They are not homozygous. 6% are compound heterozygous. And when we looked at the patients who had grossly elevated ferritins,ferritins above 1000, 20% of the males had genetic hemochromatosis, 10% of the females.

[00:38:37] Once again, the majority of patients with high ferritin did not have hemochromatosis the most common cause of a grossly elevated ferritin,at least in the west of Scotland ,was alcohol abuse and it, 10% of cases is disseminated malignancy. So that really highlights that ferritin is not a particularly useful [00:39:00] screen for hemochromatosis.

[00:39:01] It will pick up a lot of others. With the addition of transferrin saturation, it becomes more valuable, but still the majority of patients will not have genetic hemochromatosis.

[00:39:16] The clinical impact of the algorithm here in Glasgow would be that if we applied it to all the samples that we received from general practice, we would pick up 200 new cases a year. If we applied that to the whole of the west of Scotland, that would be 400 new cases. If we applied that to Scotland, we would be pretty confident with diagnosing 800 new cases per year.

[00:39:39] And that those cases would be increased by the family screenings that followed the identification of the index case. So it's a simple algorithm, it's not an expensive algorithm to apply. And it would, increase diagnosis of hemochromatosis. And these are patients of course, that are consulting their GP for [00:40:00] some reason.

[00:40:01] That encourages the GP to check the ferritin. So the conclusions, that the vast majority of patients in primary care with high ferritins don't have genetic hemochromatosis, but reflex measurement. So that if we were to automatically check transferrin saturation on these samples with raised ferritins , we could identify a group of patients that had a 20% risk of hemochromatosis and that's 44th higher than the background risk. Application of this algorithm would have a very low laboratory burden, measuring transferrin saturation costs pennies the gene test, the HFE tests, a little more, but the done in bulk is not an enormous expense.

[00:40:55] It would however, produce a clinical burden. It would increase the [00:41:00] number of patients that need to be venesected for iron reduction. And to deal with that, we need more help from the transfusion service to help us deal with induction venesections, as well as maintenance venesections. And I know the haemochromatosis society have done a huge amount of work with the transfusion service

[00:41:18] and the transfusion services now are, are more willing to see patients with haemochromatosis. Perhaps venesect them every six weeks, but for induction venesection, we're really looking for assistance in patients who for the most part are being venesected every week.

[00:41:41] And what I'd like to see is I'd like to see the algorithm that we've developed here in the west of Scotland, introduced to new areas, where there is high prevalence for genetic haemochromatosis. What about treatment? Well, the best, the best treatment is venesection. [00:42:00] And the standard treatment is where you remove 500 mils of blood.

[00:42:05] And for each 500 mils of blood, we remove, we didn't move approximately 200 to 250 milligrams of iron. That is the simplest, cheapest and the safest way of getting rid of excess iron. So that over the course of what is that 20 venesections. If we collected 20 pints of blood, we've been removing somewhere between four and five grams of iron.

[00:42:29] So if we can do that every week in 20 weeks, we've got rid of maybe something like five grams of iron.

[00:42:40] Our recommendation in the guideline was that after diagnosis all fit patients with genetic hemochromatosis, with biochemical iron loading should undergo weekly venesection and bring the serum ferritin and transferrin levels down. The aim at the end of the induction phase would be to bring [00:43:00] ferritins down to 20 to 30, which is transferrin saturations, less than 50%.

[00:43:05] And most patients will tolerate weekly venesections without becoming anemic. But to make sure that is happening safely, we would also say that the hemoglobin should be checked weekly and serum ferritin and transferrin saturation should be checked monthly.

[00:43:25] What about diet? Well, a lot of patients, a lot of patients ask me, should they modify their diets? And that's particularly a problem here in Scotland. Where our other national drink is iron brew. And it's well known that it is made from girders and full of iron. It's not, it's not, but if you go back to the original slides as I showed.

[00:43:50] I tend to advise the patients not to worry too much about the diet, just eat what they like, the amount, the vast amount of iron that's going through the plasma, [00:44:00] going into the blood every day is coming from our stores rather than from our diet. I know many of you will feel differently and strongly about it, but that tends to be my own feeling that, lead a normal life.

[00:44:12] And I'll look after your iron and venesect it as you need it.

[00:44:21] After the induction phase course, our patients  go into maintenance phase. And here is probably where the greatest dilemma arises because there are no generally adhered to guidelines as to what should be the target to aim for in maintenance fees, EASL guidelines suggest, and these are the guidelines that most gastroenterologists follow, they suggest that in maintenance fees ferritin levels should be

[00:44:49] controlled to be somewhere between 50 and a hundred micrograms per liter, but there's no, they make no mention at all of having a target for transferrin saturation, [00:45:00] hemochromatosis international. They go for the same level of ferritin, serum ferritin, but they suggest check fasting transferrin saturations twice a year.

[00:45:13] I don’t think fasting transferrin saturations have been great to offer fasting as a condition, which none of us enjoy. It's hard to get patients to comply with, in actual fact Other studies have shown it's not particularly valuable in assisting the diagnosis or the management of patients with haemochromatosis.

[00:45:32] So fasting or non-fasting, actually the predictive value for hemochromatosis as a seed, whether it's a fast itself, the BSH guidelines, However, I was involved with in 2018 and which Mark Warwood from Cardiff and James Dooley, the gastroenterologists  from London were involved with the, the BSH guidance are consistent.

[00:45:59] They say that [00:46:00] maintenance, we should aim we should monitor both serum ferritin and transferrin saturation and our target should be it serum ferritin less that 50 and transferrin  saturation less than 50%. Of course, that will all depend on the patient. You know, if patients are frail and elderly, we have to make allowances, perhaps venesection is not in their best interests, but this is for fit well patients.

[00:46:25] These are targets that we have recommended strongly in the guidelines.

[00:46:33] Why is transferrin saturation important? Why do hematologists pay more attention to trasferrin saturation than perhaps gastroenterologist do. Well, as I've said, The more, the transferrin is saturated. The more likely non transferrin bound iron is likely to appear and more cellular iron is taken up.

[00:46:55] The more transferrin saturated, the more iron will go to the liver. More iron will go to the heart [00:47:00] the more iron will go to the joints. What we're becoming aware of from the biobank study is the morbidity caused by genetic hemochromatosis is quite a bit more than we had thought 16% of males, and 10% of the females have actual symptoms and problems related to genetic hemochromatosis.

[00:47:26] And as far as arthritis is concerned, we now know that they are arthropathy  associated with genetic hemochromatosis is more likely to be seen in those patients who, during maintenance phase do not maintain it as found saturation of less than 50%.

[00:47:48] So this takes us back to the celebrity patient, and it's always good to introduce a celebrity  patient. And the reason I introduced this patient is to highlight two things. One:[00:48:00] clinically, it's very difficult to diagnose hemochromatosis from this slide it's very easy to identify the patient who is I can't, that's not a big deal.

[00:48:10] It's pretty easy to see that. And the patient that I am concerned with has is a patient who, despite keeping serum ferritin levels low runs, transferrin  saturations of 90%. So they're getting tissues, they're getting tissue iron loading. So who is my celebrity patients? Is it the Celtic little, this little chap with the Celtic features or is it this chap who definitely doesn't look like it?

[00:48:36] Well, It is in fact, Robin Dalloway and Robin Dalloway is a big supporter of haemochromatosis. He's also a very popular morning radio presenter in Scotland, and he has a very keen fan club how are very happy to venesect him when he requires it. And there's, it's usually sadness cause he faints frequently when we take blood off him.


[00:49:10] All right. So let's go back to the start. We are world. We are here. We are at start of world haemochromatosis week and we live in the world epicenter for hemochromatosis. Are we world leaders for the diagnosis and treatment? And I'm sorry to say the answer is a resounding no, we are not.

[00:49:35] But we should be. We know we have one and eight carriers, one and 150 to 200 are homozygous somewhere between 200 and 250,000 are unrecognized homozygotes throughout the UK. The awareness of the condition still remains low. Despite the very best efforts of hemochromatosis UK, it [00:50:00] is the most common genetic condition, the most common condition you've never hear of.

[00:50:07] Sadly, laboratories offer very little advice. So serum ferritin is a request that we process frequently in our hematology laboratories, but throughout the country, there's often very little comment made when the ferritin level is high, other than ferritin level is high. And there's no advice as to how this should be followed up.

[00:50:31] Okay. Iron targets and maintenance. We can't even agree on that. The iron levels, they tend to vary between different centers. They've can vary between hospitals within the same city and sadly, they can vary even within the very same hospital. So I see our unmet needs [00:51:00] and there are plenty, but I think there are two major on unmet needs.

[00:51:06] One is we have to identify more homeozygotes. The the missing diagnosis is no longer acceptable in where we are today in world haemochromatosis week. And here we are in the center, the epicenter, for genetic haemochromatosis. I also think our patients deserve specialist treatment centers, and these treatment centers would involve haematologists, gastroenterologists, hepatologists.

[00:51:35] And our transfusion specialists, transfusion nurses are the best for venesection. And the best treatment for patients is venesection rheumatology, and orthopedics could be involved for those patients who develop the haemochromatosis arthritis. One of the things that the center these centers [00:52:00] would need to accept is a need to accept adherence to the guidelines and subject themselves to auditing, to guideline adherence on an annual basis.

[00:52:16] But congratulations to haemochromatosis society, they have enabled MPs to lend all party parliamentary support. Even before Brexit was passed. I was at one of these early meetings in January, 2019. And really as a result of the efforts of the hemochromatosis UK, and parliamentary activity, hopefully their awareness of this condition will become more and more as we go on.

[00:52:50] And lastly, if you live in the west of Scotland, you'll be aware that there is indeed a Celtic or in the west of Scotland we never refer to it as being Celtic. [00:53:00] It's “celtic Curse”. And this season has been a particular curse. This is actually me visiting the stadium in Lisbon where Celtic won the European cup in 1967.

[00:53:11] But sadly, this has been a very poor season than I am still sadly affected by not the Celtic curse, but by the Celtic cross.

[00:53:22] Neil McClements (CEO, Haemochromatosis UK): [00:53:22] It was a fascinating, talk, quite technical in the early stages. So there may be some questions coming up, for those of you who are, watching the webinars live, you're very welcomed to put a question

[00:53:44] to our speaker, the best way of doing that, if you're not familiar with zoom is there's a little button at the bottom of your screen called Q and a. If you click on that, you can type in a question and if time [00:54:00] permits, we will endeavor to get round two questions coming through so thank you very much.

[00:54:06] Do feel free to, to start putting questions in, but also received some questions in advance of the session. So thank you for those of you who thought, prior to the seminar about questions. I think I've got five here, which, hopefully I can, readout and we'll get Ted’s views on those.

[00:54:26] So the first question is someone who. I'm nearly diagnosed and I've been on fortnight venesections since February. How quickly should I expect an improvement in symptoms? My main symptom is abdominal pain and tightness. So how quickly do people start to feel better, Ted?

[00:54:46] Dr Ted Fitzsimons (Consultant Haematologist): [00:54:46] Okay. It's a little difficult to answer that question without full knowledge of how high the ferritin is and how much iron loading there is.

[00:54:54] Abdominal pain is a little bit unusual. Okay. But generally speaking [00:55:00] patients, it's a condition that you diagnosed predominantly between the ages of 40 and 60. So a condition that patients have been living with for 40 to 60 years before treatment starts. So you can't expect 40 to 60 years of gradually on accumulation to correct itself particularly quickly.

[00:55:22] I generally say to the patients, who've got significant iron loading. You will start to feel better within the year of the venesections, but I'm not to expect too much too quick.

[00:55:36] Neil McClements (CEO, Haemochromatosis UK): [00:55:36] Great. Thank you. Hopefully that answers that question. The second question, that came in, asks not everyone with hemochromatosis is lucky enough to be under the care of a hospital consultant.

[00:55:50] For those of us who rely on being a blood donor and have a low ferritin of 18 and a high transferrin saturation of 58%, how best can we [00:56:00] balance the two and ensure that no damage has been done?

[00:56:06] Dr Ted Fitzsimons (Consultant Haematologist): [00:56:06] That is the most difficult group that patients who despite being low ferritin

[00:56:15] tthat's low, normal.This still has a high transferrin saturation. And I think these patients, I manage on the borderline of iron deficiency. It's the only way we can do it, but, the transfusion service, although they will venesect the patients regularly, they won't take clinical responsibility.

[00:56:39] So generally speaking, certainly the case is in Scotland is that, the transfusion service will venesect still for the moment every three months. Hopefully it will get down to every six weeks shortly, but for the moment, every three months, but for the patients themselves, they continue to be seen by myself and my colleagues at the hospital [00:57:00] on a six monthly or annual basis.

[00:57:01] So although the patients are under venesection with the transfusion service, the clinical management remains with their clinicians in secondary care.

[00:57:15] Neil McClements (CEO, Haemochromatosis UK): [00:57:15] Great. Thank you. Now we have a question with, and this is a slightly technical one, so I'm going to have a go at pronouncing it, but we have someone who is concerned about the incidence of PCT in people with hemochromatosis.

[00:57:29] And for those of you who are watching, who don't know what PCT is, it's actually a short, an acronym for something which has Porphyria Cutanea Tarda, hope I pronounced that correctly. And I myself have had this. actually, and it's very unpleasant. It's a bit like having chicken pox. Um, and it particularly starts at this time of the year when the sun comes out, for reasons which perhaps Ted might explain a bit more, but Ted, do we know roughly what is the incidence of PCT and people with haemochromatosis?

[00:57:57] Well,

[00:57:58] Dr Ted Fitzsimons (Consultant Haematologist): [00:57:58] thankfully it's a low[00:58:00] thankfully, but it is low, it is an iron related deficiency. And most patients with PCT don't have haemochromatosis. They've got iron problems for other reasons, but you're right. It's a light sensitive eruption on the skin, which is unpleasant can be quite disfiguring as well.

[00:58:21] It's controlled by venesection, and then reducing the amount of iron it relates to your iron, iron is required by your cells to form heme. And in the process of heme synthesis, porphyrins are produced and PCT as porphyria, excess porphyrins, cutaneous ta-da is.

[00:58:51] Cutaneous in the skin, with burning and with damage. So it's, it's, [00:59:00] it's an uncommon complication. I don't think I have a patient with hemochromatosis and porphyria cutanea tarda but I do have patients with  that who don't have haemochromatosis, but it is, it's an unpleasant condition.

[00:59:16] Patients with hemochromatosis are more prone to it because of the iron loading and the treatment, the best treatment for it is venesection with iron reductions.

[00:59:27] Neil McClements (CEO, Haemochromatosis UK): [00:59:27] Not steroid creams. As I was prescribed, it makes it worse.

[00:59:32] Dr Ted Fitzsimons (Consultant Haematologist): [00:59:32]It is a difficult diagnosis. It is. Yeah.

[00:59:36] Neil McClements (CEO, Haemochromatosis UK): [00:59:36] It's not common, but it's very unpleasant. If you get it.

[00:59:39] let's move on to another question, that we received early and then we'll turn to the ones in the Q and a. This question is actually from Alison who's an honorary senior research fellow at Cardiff university. Alison asked in Dr. Fitzsimmons view, what achievable action by NHS staff does he think would provide the most [01:00:00] benefit for those affected by hereditary and undiagnosed, but presumed hereditary haemochromatosis.

[01:00:07] So what can the NHS be doing to help?

[01:00:10] Dr Ted Fitzsimons (Consultant Haematologist): [01:00:10] Well, I am very keen on introducing the algorithm here to the west of Scotland and I was quite fine along the road. To doing so when COVID came to visit and every PCR machine in the west of Scotland that was not essential was then switched over to COVID.

[01:00:47] So you're the HFE gene. You're the detection we'll meet PCR testing. I would like to think that the algorithm could be [01:01:00] introduced and that we would start in areas of high prevalence and that we would increase the detection for patients in primary care. Why we focused in primary care as a primary care, the patients are generally, a healthy population.

[01:01:15] And in secondary care, there's so many other factors that can contribute to causing high ferritin. You have the cancers, you know, the renal dialysis, the advanced liver disease. I personally, I would like to, I am keen to introduce the algorithm as far as treatments are concerned

[01:01:39] it was Alison Alison maybe has asked the question. She was the one that, raised the topic of specialist centers, for treatment of patients with genetic hemochromatosis. I think that's an absolutely great suggestion that these patients should be cared for by a multidisciplinary [01:02:00] team that involves, hematologists, gastroenterologists, rheumatologists, scientists,

[01:02:05] transfusionists so those, those are little steps. And the part of the transfusion service, you know, it would be great to get more help on venesection during induction phase. You know, most of my patients have after diagnosis, if they've got significant iron loading, will go onto weekly venesections.

[01:02:30] We have to throw these blood, these units of blood away. You know, these units about can contain very, very little iron from just one unit of blood. And I can't see any harm in the vast majority of these units not being used, therapeutically for patients who require transfusions.

[01:02:53] I'd like to see the algorithm introduced. I'd like to [01:03:00] see specialist centers and I'd like to see the transfusion centers becoming more involved.

[01:03:10] Neil McClements (CEO, Haemochromatosis UK): [01:03:10] Great. We have a question from Sean, which is a Tsat type question.

[01:03:15] Sean says I'm on a maintenance program with four or five intersections per year. And my ferritin is in the 50 to 70 range. I've no idea about my transference saturation because the hospital tells me there's no need to test it regularly. Any the advice as to what I should do?

[01:03:36] Dr Ted Fitzsimons (Consultant Haematologist): [01:03:36] I would imagine that the  gastroenterologists tend to pay a lot of attention to ferritin, hematologists pay attention to ferritin and transferrin saturations. So,you, the patient is entitled to see the BSH guidelines, which were [01:04:00] produced by a combination of haematologist, and gastroenterologist have emphasized the importance of controlling feral saturation as well.

[01:04:08] All right. Why don't you do that?

[01:04:11] Neil McClements (CEO, Haemochromatosis UK): [01:04:11] So, sean.If it's an NHS hospital, there's usually a team called pals, which has patient liaison service. And if you're not able to get hold of your consultant as is often the case, if you get the hospital pals team a ring and raise your concern with them, they will often, interact on your behalf and help to work that one through.

[01:04:31] So just a practical issue. Ifyou ever run into any trouble, with, testing in a hospital situation? The NHS usually has a pals team, P A L S if you contact them, they may be able to help you. Another question, has come in from anonymous, should premenopausal women who are C282Y homozygous with a very high Tsat level and borderline ferritin level of just over 200 start venesection, or should they wait until after menopause?

[01:05:01] [01:05:00] Dr Ted Fitzsimons (Consultant Haematologist): [01:05:01] I’d start, I as a hematologist, I am concerned. I do pay attention to transferrin saturations, it’s the transferrin saturation the substance fan saturation that determines the amount of iron that's going, to the tissues. It's the amount of iron that’s going to the tissues that is causing toxicity.

[01:05:21] The sooner you stop it the better. So my own feelings, you don't wait. You anticipate that the venesection requirement will increase for awhile. But then there is, an aging effect on genetic hemochromatosis. One, which I can't explain, except it, unless aging is a equivalent to a sort of chronic disease, but there's no doubt about it for reasons that we don't exactly understand the older patients with genetic hemochromatosis gradually find the a reduced need for venesection.

[01:06:03] Neil McClements (CEO, Haemochromatosis UK): [01:06:03] Joanna asks, how important is it that those of us with transferrin saturation, which fluctuates wildly between 60 and 80% should be continuing with venesection even though the ferritin levels around 20 to 30.

[01:06:21] Dr Ted Fitzsimons (Consultant Haematologist): [01:06:21] it's difficult. And in these cases, I tend to monitor the hemoglobin as well.

[01:06:29] If you can run with a hemoglobin that's unaffected with a ferritin down at 15, then you're running what we call latent time deficiency. You just live on the cusp between iron deficiency and, non anemic. So these patients, I have a group of them and I see that these patients have just have to run with borderline iron deficient ferritin values.

[01:07:00] [01:07:00] Neil McClements (CEO, Haemochromatosis UK): [01:07:00] Great. Thank you. Just in relation to your earlier point in touch about aging, Mary asks the question, why are the elderly not venesected so often and therefore get higher levels as it affects the bones and the heart?

[01:07:13] Dr Ted Fitzsimons (Consultant Haematologist): [01:07:13] My observation over many over years is that as the patient get older their ferritin seem to stop rising and transferrin

[01:07:26] Saturations remain satsfactory, and it is your hepcidin. If you have chronic disease your hepcidin levels are increased. And I think what seems to happen is that as we get older,  the body recognizes aging as a type of chronic disease and somehow gets round the deficiency of hepcidin and that [01:08:00] genetically the haemochromatosis patient has and produces some factors that act in the same way as hepcidin.

[01:08:12] But certainly elderly patients who continue to iron load should be venesected, as long as they're well, and able to withstand.

[01:08:23] Neil McClements (CEO, Haemochromatosis UK): [01:08:23] So hopefully Mary, that gives you a bit more ammunition if you need it to go and talk to your consultant.We've got a question from Sally van Rees, Sally is actually a haemotology specialist nurse

[01:08:36] So there's lots of people interested in genetic hemochromatosis, not just the patient community, but Sally is a hematology specialist nurse, and has recently started a nurse led GH clinic. And she's in the process of writing a local protocol. She asks the question, Tedhow do you move forward with patients whose serum ferritin responds, but tea sets remain stubbornly high as they approach maintenance?

[01:09:00] [01:09:00] Dr Ted Fitzsimons (Consultant Haematologist): [01:09:00] Yeah,  so it's interesting that there's definite concern among the law with a lot of these questions on Tsat and to be honest I’m quite Glad to hear of patients being aware of it. I don’t mean to repeat myself, but I think these are the patients that have to run borderline iron deficient. You have to get them to a level where their ferritin level is low, but the hemoglobin level is adequate.

[01:09:27] Neil McClements (CEO, Haemochromatosis UK): [01:09:27] So keep venesecting basically. Just by the way of a quick plug, we actually, we send out hundreds of these to GP’s:Tsat matters. GP’s love post-its. And that’s how we get the message across. We've got a question here from anonymous. Anonymous says my children's GP refused to test them for the GH gene, even after my end diagnosis.

[01:09:51] And we'll only test for serum ferritin. What can we do to persuade the GPS? My two sons already display some symptoms.

[01:10:01] [01:10:00] Dr Ted Fitzsimons (Consultant Haematologist): [01:10:01] I advise the GP that there are BSA guidelines that specify that checking for ferritin and iron hemoglobin is not adequate and that the first degree family members should include, uh, the genetic screen.

[01:10:25] I don't know how else to do it. It's in the BSH guideline. It was agreed by hematologists gastroenterologist. Then it goes to a panel for review and the guideline was accepted.

[01:10:42] Neil McClements (CEO, Haemochromatosis UK): [01:10:42] Yeah. So keep pushing the GP. For those of you who are members of huk, you may be aware that we as a charity have recently started a genetic testing service.

[01:10:56] And if you're a member you can order [01:11:00] one of our genetic testing kits. We call them spotty dottie's for obvious reasons, everything in there will do a genetic test. For adults and children, you can order them on the website. If you're a member, we subsidize these, right. So I am not selling you this to make money.

[01:11:14] We actually subsidized these, but we launched this project actually just two or three weeks ago, and we've been overwhelmed with demand, but the first set of results came back, at the end of last week. And we have found that almost four in 10, almost four in 10 people who have done their genetic tests through HUK have got genetic hemochromatosis.

[01:11:37] And were unaware of it. Okay. So there is value if you, if you really get stuck with your GP and I'm not here to, you know, to sell you anything, if you're a member, you can get one of these kits. We have done, hundreds of these over the last three weeks, and we turn the responses around, within about 10 days.

[01:11:56] So if you're worried about it, you don't have to wait too long to get the answers. But, [01:12:00]  if you're interested in that, go to our homepage at the website and you can order yourself a kit for your children if they're an adult, okay let me just see, we've got a couple more questions have come in.

[01:12:11]  My wife says anonymous. My wife age 71 has serum ferritin around 400, but has tested negative for genetic hemochromatosis. I think alcohol abuse is unlikely to be the reason. So what should she be tested for and what are her risks?

[01:12:31] Dr Ted Fitzsimons (Consultant Haematologist): [01:12:31] Generally, these patients will not have a high transferrin saturation, and it's an isolated high ferritin, and it's not a terribly high ferritin at 400. One of the things you think about is to liver disease, fatty liver is very very common. And,the alcohol, you would know if alcohol was a problem as it's not that, fatty liver, [01:13:00] that would be something, some sort of low grade arthritis would push up ferretin levels.

[01:13:04] But by and large, if, if you've got a ferretin of 400 and  transferrin saturation, that's normal, I wouldn't be too concerned.

[01:13:12] Neil McClements (CEO, Haemochromatosis UK): [01:13:12] Okay.Marcus question about osteoporosis, mark wants to know, is there any study that throws light on the connection between the hemochromatosis and osteoporosis?

[01:13:26] Dr Ted Fitzsimons (Consultant Haematologist): [01:13:26] Not an association that

[01:13:28] immediately comes to mind.

[01:13:30] Neil McClements (CEO, Haemochromatosis UK): [01:13:30] Mark, if you, if you go onto our website, we've been very busy over, lock down because we weren't allowed out. So we spent a lot of time writing, and commissioning new booklets, but there's a booklet on,  joint pain, arthropathy and osteoporosis, which was written by someone who I think Ted knows very well at Dr.

[01:13:49] Patrick Kylie at St. George's medical school in London. It's got some very interesting material in there. It's not a medical research study. It's really designed as a guide for people who are [01:14:00] experiencing joint pain, to help explain why it happens and some of the things that help, to reduce that pain.

[01:14:06] So if you're interested in that, it's in our membership packs. If you're not already a member sign up, we'll send you one. It's also available for free download on our website. If you go to all of our booklets are published online. So hopefully that will help you get to the bottom of that.

[01:14:24] We've got a couple of questions here,in relation to, testing, which we'll come on to, but Gabriel asks, he's on his, maintenance phase and his ferritin is below a hundred. He had problems getting the information needed to complete the forms to become a blood donor because he wants to switch from doing venesections in hospital.

[01:14:48] His question is how can we increase the hematologist training in the protocols to transfer patients across NHS departments?

[01:14:59] Dr Ted Fitzsimons (Consultant Haematologist): [01:14:59]  [01:15:00]I can only speak for the Scottish experience and in Scotland, transferring a patient from a hospital  to transfusion service  is very easy. It's all done electronically with a referral form, which the hematologist completes or the gastro gastroenterologist. It's a very simple form.

[01:15:26] And the transfusion service then have a telephone consultation to make sure the patient is searchable. You know, not all patients are suitable and maybe some patients who've had previous transfusion within the past 15, 20 years. The transfusion service can accept them. Patients with some medical issues or previous cancer can’t accept them.

[01:15:51] But the vast majority of patients that read affair to transfusion service are accepted and it's a very easy procedure. [01:16:00] I'm not sure how it works down south. S

[01:16:03] Neil McClements (CEO, Haemochromatosis UK): [01:16:03] it's different in each region, which is where some of the complexity arises, but actually for those people who may be watching, who are based in Scotland,  the forms, which Ted is mentioning, we actually have copies of those forms.

[01:16:16] Sometimes, doctors aren't able to locate the forms on the NHS website So we've helpfully put them in one place. And for those people that are actually living in England, who aren't aware we did actually negotiate a very comprehensive GH donor scheme with NHS blood and transplant this time last year, um, all the details are on our website.

[01:16:36] If you go to , can I donate blood? All of the information is there and we keep that up to date because I think as Ted has alluded to the conversations are going on between the charity, and clinicians like Ted and also the blood services on an almost daily basis.

[01:16:56] So we're continuing to push for improvements, to allow people to [01:17:00] donate if they have genetic hemochromatosis. So the picture does change over time and it is,  hopefully changing again shortly in Scotland. It's changed quite a bit in England and in Northern Ireland, it's working very well as well.

[01:17:11] So have a look at our website can only donate blood? and that will hopefully point you in the right direction. I think we've got time for a couple more questions and then we have to let Ted go because he has a clinical appointment shortly.  But this question is coming from Michelle. Michelle says she was diagnosed in December, 2019 with a ferritin count of 1,555.

[01:17:34] Last week. She was diagnosed with underactive thyroid, are the two directly related?

[01:17:43] Dr Ted Fitzsimons (Consultant Haematologist): [01:17:43] Well it's possible, but it's not strong. Hypothyroidism is so common, in the community that it's possible.  Jeff [01:18:00] hemochromatosis does cause endocrine abnormalities, but the association is, not particularly strong and it's more likely that the hypothyroidism is auto immune.

[01:18:10] That's due to antibodies that are produced against the thyroid rather than to iron Auto-immune hypothyroidism is by far the commonest cause of hypothyroidism.

[01:18:26] Neil McClements (CEO, Haemochromatosis UK): [01:18:26] Okay, hopefully that,  helps shed some light for you. I think our final question before I pass it back to Ted to, to make any closing remarks.

[01:18:37] So the final question is, is genetic testing recommended to young children under 18 years old? I'm thinking whether I should test my two year old son.

[01:18:49] Dr Ted Fitzsimons (Consultant Haematologist): [01:18:49] No, I wouldn't. I wouldn't do that.The guideline that we produced suggested that children should be checked when you [01:19:00] reach the age of consent and haemochromatosis the demands of the body for iron, as you're growing are so huge that

[01:19:13] the iron goes to the growing body rather than to the tissues and toxicity. So problems with haemochromatosis, rarely present before the age of 30. So the two year old child, definitely not. When the child reaches age of consent and it happy to get tested.

[01:19:33] Neil McClements (CEO, Haemochromatosis UK): [01:19:33] Excellent. Okay.

[01:19:34] Well, I think that's all the time that we have for questions now, Ted I wonder, do you want to make any closing remarks

[01:19:42] Dr Ted Fitzsimons (Consultant Haematologist): [01:19:42] First is an apology to Alison May I should have mentioned you , together with the three men for when I was just a shepherd. You were certainly in the stable as well.

[01:19:54] So, Alison has done great work on iron and [01:20:00] hemochromatosis, and she, as much as Alan Jacobs, stimulated my interest in iron  when I was in Cardiff. And I think we're at a stage where things are changing for hemochromatosis. I think that changing as a result of  what Neil, you, and hemochromatosis Uk are doing as a result of what we're seeing from the UK biobank and the gene studies that are going on.

[01:20:34] And I think the story may all be quite different in five or 10 years time. I think awareness of the condition is increasing. I think the need to find the missing patients and missing homozygotes. I think that's now being recognized. And I think we have an opportunity now as I said, This is world hemochromatosis week.

[01:21:00] [01:20:59] Here we are the world epicenter for hemochromatosis. It's about time. We took some bold steps forward to become leaders in diagnosis and treatment. Instead of this very fractured approach, that there is where even within my own hospital, the practice of looking after patients with haemochromatosis is different between hematologists and gastroenteroloigists.

[01:21:27] Neil McClements (CEO, Haemochromatosis UK): [01:21:27] Well, thank you very much Dr. Ted Fitzsimmons, that's been a really enlightening,  90 minutes or so, and we thank you again,  for your time. We know how incredibly busy and stretch you and your colleagues are in Glasgow at the moment, particularly with COVID. So thank you again for taking the time to share those thoughts with us.

[01:21:46] For those of you who are interested in the recording, just as soon as we get a chance to edit it, we will put it up on our YouTube channel and because it's world hemochromatosis week, we're just on day one.So I just wanted to flag up a couple of things [01:22:00] that are going on this week. There's a lot going on this week.

[01:22:02] The phone hasn't stopped ringing in the office, since we came in this morning. But for those of you who are based in Cardiff or within striking distance of Cardiff,  Cardiff city council is very kindly offered to light up, Cardiff castle in HUK red. Tonight. So if you want to see kind of castle bathe and red light, as an awareness raising thing, grab your friends, grab your family, providing a socially distance, go down to Cardiff castle after eight o'clock, there'll be switching the lights on,  to commemorate world hemochromatosis week.

[01:22:35] And the other thing I just want to draw people's attention to. We have a couple more seminars this week with some places available. We have a discussion going on on Thursday at lunchtime, UK time, which I will be chairing, which is looking at the international dimension of genetic hemochromatosis.

[01:22:52] And I'm delighted to say that we're going to be joined by representatives from not just the UK, but also the Republic of Ireland, Canada and Australia. [01:23:00] So I'm hoping that will be a very informative discussion because actually how each country,  diagnosis and treats hemochromatosis is actually quite distinctive.

[01:23:09] And if you're not familiar with how that works in other parts of the world, and you're interested do come along all the details for joining it's a free seminar on Thursday. And then also on Friday, I just want to draw attention to Dr. Bill Griffis, from Addenbrookes hospital here in, England.

[01:23:26]  Will be presenting on some latest research that he and his team have been doing around using MRI scanning techniques to actually diagnose people with haemochromatosis. So if you're interested in that, that seminar again is free for everybody to turn up. You just need to pre-book pre-register on our website, go to the What’s on page and that is,  11 o'clock on Friday.

[01:23:48] And finally. We are a charity. Okay. So it would be remiss of me not to ask for donations. So if you're not a member and you think that this has been useful to you in some way or other, we'd be [01:24:00] very appreciative. If you want to make a small donation on our website, we'd be very grateful for that. And we'd be particularly grateful if you want it to sponsor our amazing membership administrative Vicky.

[01:24:10] Vicky has decided to throw herself out of a plane on Saturday with a parachute. She's not done it before.We're hoping to get to about 1500 pounds to enable us to send the plane up to 15,000 feet. So if you've had some benefit o you think the seminar has been useful, and you'd like to chip in a little bit, do go to our website, have a look for Vicky's fundraising page.

[01:24:33] If we can get 1500 quid by Saturday, the plane will go to 15,000 feet before they throw her out and again tremendous admiration for Vicki for doing this because actually I wouldn't be seen dead in a plane with a parachute unless of course there was a problem with the plane.

[01:24:51] So, thank you very much,  for those of you for attending today,  we hope you have a wonderful week. Do keep following us on [01:25:00] Facebook, on Twitter. There's lots of stuff going on, which I haven't talked about, but we really do welcome you. And we encourage you to reach out to your friends and family and your colleagues to help raise awareness of hemochromatosis because at the end of the day together, we're stronger.

[01:25:16] Thank you.