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ago. Sorry. Love in you is that he may So I'm good to go, But I can't hear you to see what your instructions are. We'll muddle through. Sorry. Definitely are good to go. Yeah. Okay. Hopefully can appear Me If there's any people who are struggling to see where I'm showing or any probably sound, please let me know in the chat on we can get cracking. Okay, so I've been asked to talk. So I'm James, and I'm one of the pediatric rheumatologist over a great Ormond street. Um, Onda, uh, anemia is a question. We get a lot. Surprisingly, this is Ah, General focus on my focus just on pediatrics across the board. It's predominantly to try on get you guys to a point where, um you have some understanding off how to approach anemia when you see it. Um, we get a lot of referrals about anemia. Andi people have a range off ways of approaching it. On my way may not be your way, but I want to give some structure too. This enormous beast is this enormous? A wreck array of um, of course, is Onda everything else and people really struggled to get a handle on that one and then to use that understanding to think What are the basic tests that would be helpful when when investigators for the first time, um, what information would be very useful if you're referring to hematology trying to phrase your question in the right way and to say, I've done some basic work up because this is a very common topic, and it should should be within your understanding. Okay, so I'm going to go. I know we have a range of different people, and people's engagement with hematology and hematology concepts could be quite variable over the course of medical school. Early medical training, where some people really grasp the basic concepts and some people just because it's not high yield because it doesn't come up in Data Brothers. It's not always embedded very well. What on earth is going on? So just to go back and back a bit, we've got our bone marrow, which produces from our hematocrit extend cells, the main blood, um, lines that we have. So we have the red cells, we have white cells and we have plates. And obviously, with that focusing on the red cells, a day and the production of red cells is called a wreath. Throw poisonous, and there's quite important to get your head round this to some extent because you can see that we start off with the's pluripotent. Potent stem cells that rapidly differentiates on becomes evermore mature and different, differentiated on be more towards a professional cell where they'll end up being on the myeloid. Siris encompasses not only red cells but also platelets on, but majority off nonlymphoid white cells. So they there's a lot of overlap with those conditions with Milo Proliferative and changing conditions. But going down just a purely the Lyme leads to a red cell. You can see that within the bone marrow, you start getting the early erythroblastic, which then become evermore differentiated on. Then, at the point where they their nuclear good red cells, they lose their nuclear to become a non nuclear cell on those very early cells still have quite a lot of abundant RNA. They've lost their DNA with it because I got abundant irony on they are ridiculous sites, and they haven't haven't quite form the A, um the classic biconcave shape of red cell on there a bit more purplish in the other states because of that, so you end up seeing those. And it's important to understand that the reticulocytes are the last phase before the red cell, because if the bone marrow is being stimulated to produce more red cells, Morris, the precursors will be moved out from the bone marrow into circulation. And we'll come back to that concept shortly. So what does anemia mean? And it basically on meaning without on anemia, blood is just absence of blood. But there's it's very difficult to define a very broad sense to space. It means you've lost your red cell mass, but in a functional sense, it's actually a lower ability off your blood to carry oxygen. So you become anemic in that way. Um, but again, the definitions a rub it vague, and they will come with their own problems on a pill. A technical level, you could say it is, too stands deviations between the normal age for normal, normal for age and sex because as you are born moving into having adult hemoglobin on, then having establishing marrow on, then as you grow go through puberty, you'll have fluctuating counts. Um, women and men, Big, non pregnant women and men have a very different cut off on D. There have historically bean thoughts that perhaps there should be different cutoffs for different genetic background ethnicities. But actually, that's probably more a sign of missing things and and not treating things thoroughly rather than they're being true differences. Who actually this largely scraps that idea. Um, in terms of the wh Oh, these are the threshold that they put out there in the stands of grams per liter, so normal, being about 120 ish on. But there are ways of categorizing into mild, moderate and severe, and that can be useful. But the most important thing, really is your ability to understand on a clinical level to them, evaluate for symptoms. Because actually, all it comes down to really is you shouldn't be chasing a number. You should be chasing what impact it has on the patient and being quite being a bit more open to investigation. If it's not just one or two below the national the reference range, but very much lower. Um, I was also going to examine you is really tough to measure Red Cell Mass, which is why we use proxy markers like the hemoglobin concentration, which is obviously, you know, problematic if you look at hemoglobin, ft's and other other things there, or things like hematocrit and things like that. But I wasn't going to delve into the full blood count today. But I can do if that's interesting for other people. So there are many approaches to the categorization off anemia. Okay, um, some people like to use the appearance on blood film. So looking at the size of the red cells, whether it's Mikus if IQ normocytic or macrocytic toe categorize things on, that can be a very useful approach, particularly you're trying to use test to guide you down one way or the other. But actually, when you're looking at, I think the most important thing is trying to understand what's going on. So you have your bone marrow producing red cells, and it should be producing enough to carry, um, your desired oxygen to the body on not leave you with in deficit. You know, if your peak pediatric patients starting to thrive, if you're older, patient starting to do exercise and things like that, Um, so you have your production and you can have a lack of production. No bread sales, like all cells, have a lifespans around 120 days. But if those cells are in some way ineffective, so they've been there, this erythroblastic. So the process of production has meant that they are not produced well, and they are dysfunctional on D, more vulnerable to the stresses and strains of being circulated around the body. Then there that lifespan will be less so they'll be removed earlier. That can also be other reasons that they can be removed from circulation by the natural processes, which is your reticuloendothelial system. And just spleen, which can be immune mediated, meaning that the cells are removed by a stimulated immune system that recognizes those is for um, which is where the auto immune on sometimes aloe immune meaning the immunity is coming from outside wear. Um so hemolysis the breakdown cells can come from, and then you can also just have the fact that red cells could be lost from circulation, which is blood loss, and actually that is the most common cause. Eso it's important to try and understand. Is this a lack of production, increased destruction Or is it loss on that? To my mind, the most helpful way of understanding the catherization. But there are different ways to approach it. Okay, so looking first of the most common things, which is blood loss Okay on that could be very, very apparent. Someone has a car crash. They're hemorrhaging. They are clearly losing blood. They need lifesaving transfer, transfusion and, you know, urgent hemostatic management with that be surgical or otherwise, to control the bleeding. And in that security situation where you've got acute blood loss, you won't really see many changes apart from the fact that the red cells and the hemoglobin construction and all the parameters will just go down. But you won't see the chronic changes. They'll still be the right shape, shape meaning normocytic. So the right size and normochromic meaning that they concentration of hemoglobin within those cells remains saves of the enormous cytic. You may see the bone marrow trying to compensate. It's losing all this blood on the bone marrow. Say, hey, I need to produce more, so you will get that increase off production on. Then you'll start to see that spill over off the slightly that one or two stages before the red cells spilling out as it rushes to produce and pretreatment circulation. So you'll start to see some of those particular sites, and you'll start to see some potentially some nucleated red cells and potentially some earlier precursors, as the body rush is the drawing fill that void, but you won't see that within the first few hours. It takes a while for that, your body to detect either hypoc, CIA or other things that stimulates a refill for eaten on causes that process that happen okay on. That's normally the history examination. Fairly clear cut. What's going on on If you can't see that, you know, perhaps learn all the color it is chronic blood loss is a bit more difficult sometimes to pick up. It can be a really mishmash of things, but you do start to see some trends, so you start to see signs that your your blood is being lost. And as you're not having any Seroquel, Patrick recirculation off iron. You're losing that ferrous on my own. Um, your body's actually pretty rubbish absorbing iron from his diet on, so you'll start to see signs that the body doesn't have enough. It's losing it wherever it's losing it. Whether that be GI I loss is whether it be menstrual losses. Whether it be, you know, genital urinary loss is or anywhere else. The iron isn't recirculated. You start seeing the tronic signs off. I am depletion, which is started. See the MCV come down because the red cell is not packed enough with with hemoglobin on, so it just doesn't fill out a couple cycles government doesn't fill up on. Then you'll start to see the same things where the mean called postular hemoglobin. That's not him. Globin is low, the mean corpuscular hemoglobin concentration is also low, and you'll start to see that the iron markers going most particular ferret in which is obviously an acute phase, reactant so very difficult best biking, fevers or infected or anything else. But you can also see something like a total iron binding capacity or the trans fat saturation be very, very low, and we'll have these hypochromia mc acidic red cells under the blood pill, and that can be a science going on. You may have a reduced ridiculous I count because the marrow doesn't have enough to produce, but that's chronic blood loss is. And you know, if you're getting a picture of iron deficiency anemia, the mainstay of management is figure out where that blood loss is. So you know, in the classic 50 year old male, you're going to be thinking, this is GI I cancer until proven otherwise. In a 25 year old woman, the first thought is that she's having heavy menstrual Aussies on his losing blood. There is iron there, but there's all sorts in between. Don't forget your celiac screen because having that atrophic gastritis and journalists can lead to poor absorption on, you need to think about those sort of things as well. But having a a broad, real it of wag looking for these things on thinking about, you know, should they have another GD? Should they have a colonoscopy? Should we be investigating? Appropriately? So that's the most common cause, but actually the easiest one to review that it's actually mainly on history examination on thinking about, you know, some basic blood tests of iron studies. Um, the next one is decreased production where the bone marrow just isn't able to produce bread cells for whatever reason. Okay, Onda the most useful tests that you can really use toe. So pick this up would be getting a reticulocyte count, because if the ridiculous I count is very, very low compared to the anemia is obviously if there's anemia, you'd expect the bone marrow to be trying to increase its production, so you would probably see a ridiculous psychosis so it would be above the reference range as the marrow tries to keep pace with blood loss. But if there are particular sites are low on D is anemia. That's a disproportionate particular cytopenia. And you need to think, Is there a production problem now? The most common things apart from the iron deficiency that we just talked about would be a hematinic deficiency. So the building blocks just aren't there on D. As a knot there, your body cannot produce enough red cells. Okay, so this is where we move on to be 12 and folate, which are very, very commonly low. And with B 12, you you have to think about, you know, is there enough in the diet, which is actually the most common, particularly elderly people on nursing home residents. You may have calories going in but not having other things on. Do you need to consider a placing that, um, if it's very severe with B 12 deficiency, you will start to see a neurological problems as well with the weakness and everything else. So it's important thing to pick up so late is another one that can lead to a megaloblast IQ anemia. So basically, you get the scientist gets and produced, and it was, you know, getting up with hemoglobin. But it's just struggling to be, you know, that for the entire DNA synthesis to come in, and so you end up with a problem. It's called megaloblast IQ, because when you look under the microscope, particular bone marrow there characteristic changes on what you'll see is ah, multi load neutrophil and macrocyte. It's on. There are other cause of macrocytosis, which will come on two shortly. But if you're seeing a megaloblast IQ appearance and you see that in the Blood film report, what's the reporter was trying to tell you is that there is clear morphological visualization of the cells. Evidence off, uh, the B 12 or folate deficiency on. Don't forget. If you have a mixed deficiency, you do not want to be in a situation where you run out of B 12 because if your both deficient and you replace the folate, not the B 12, you're suddenly kick into gear and use up. Every bit of B 12 was left with the photo going in, and you become profoundly B 12 deficient, and you then end up with neurological problems, which may be irreversible. That sub acute combined generation court. So always replace B 12 1st on, then think about replacing the phone 24 hours later. The other thing you need to think about with B 12 it is a common thing that comes up is pernicious anemia, and what this is is that you've lost your intrinsic factor and you're not able to absorb it on. The reason is simple. To think about is that you can only really diagnose the intrinsic factor. Antibodies on a blood test prior to giving B 12. Is it exalts? Confound the results and the reason that's a relevance is that people who have deemed B 12 deficient and I'll start intra muscular injections for B 12 and they have a dietary deficiency could well easily be replaced with or a B 12 and appropriate multi vitamin in the future, which have all avoids the whole rigmarole of going to the GP for Jurassic injection. So it's if you are suspecting, if there's clear evidence of dietary deficiency, it's probably worth while thinking about sending intrinsic factor antibodies before you give the B 12 just to rule it out. So they're not condemned, toe. You know, no one thank you about it and giving them beat or injections for life, which happens more commonly than we would like. Yeah. Now this is also where thyroid function concomitant causes the macrocytic anemia on. Do you need to think about TFT is well, you know, I explained anemia, so that's recent. Okay, There are other things that can lead to a decrease production. Okay, No, only the building blocks being absence, but also on anemia of chronic disease. So this basically leads to a chronic inflammatory state off some description where that comes from, renal disease, liver disease, malignancy, you know, chronic inflammation from him. Thought because there's anything else you get up. Regulation of helps it in, which is the main molecules involved in the regulation of iron uptake in metabolism and so basically, just don't utilize your iron very well. You end up normally with enormous cytic anemia, but you just get normal indices, but just, um, anemia. And if you're looking for those factors, you can normally find it quickly. Then you might get a ridiculous that opinion as well. The mainstay of management is actually sorting out online course. Then we come on two other more sinister causes, which is why people worry about in your in the first place, really, other than becoming symptomatic, which is some process infiltrating the marrow Now there are all sorts of things that can do this. Solid tumors can sometimes infiltrate American, get bony metastases that crowd out anything else going on there? But you can also get married filtration from him, too. Logical malignancies on that. So cancers lymphoproliferative disorder on. But you know things like myelofibrosis and other things where the substance of the marrow is replaced by non functional tissue of some description and you get a decrease. And a blood film can be very helpful in your circumstance to try and evaluate whether there are leukemic cells or anything else, or even signs of stress in the mirror in the absence of anything else, which would be a first line investigation. But it depends on the circumstances. But sometimes we would also start thinking about doing a bone marrow aspirate in that circumstance. If there was, if it was indicated other from him for prospective orders to get diagnosis was going on. And then we got into the really rare stuff, which is actually comes up in exams quite a lot because it's quite interesting. But I don't want people to get too excited about because it is weird and wonderful on the's. A bone marrow failure syndromes, which can be acquired, um, which normally come from medications or chemotherapy or toxin. So even alcohol is actually a way of getting married failure because it's just not producing anything infection. On by this, I'm talking about things like parvovirus CMP on other parasitic infections that can infiltrate there. So leishmaniasis on go travel histories and thinking about those it is very important and also get married failure. If you're profoundly septic, a well and you'll often see the cooking in context in the history giving you those things, then you have things like acquired a plastic anemia which I'm not going to delve into today because it is no ah, lifetime of research in his own right. But this is where there's normally an immune mediated pathology that leads to a lack of reduction of all cells are not just red cells. You can also get just a simple limit effects, but it's quite rare, but it does require quite a lot of work up to sit around. Then you have the myelodysplastic syndromes where genetic errors creep in on the lead, the bone marrow failure with time on. Then we have other rare things that PNH which you probably know, see a case of in your lifetime. But that can also lead to a plastic anemia type of condition going forward and let me move on to the inherited bone marrow failure syndromes, which very rare. And you really, really encountered, Um, no, a few times in a in a career, Really, Unless you you wanted to the lovely well, the pediatric rheumatology. I mentioned them. Just so you have some idea where these names fall into, I'm not gonna go into. No one would expect any of this to be routine knowledge. It's more just an understanding that people are presenting pants like a peanut on a malignancy has been ruled out. You may be looking younger patients start to think about bone marrow failure syndromes, and there are various things you can think about them that long. Okay, Uh, right on. Then we move on to losses, and that's predominantly hemolysis, which is actually an area which is much heart from blood loss, which is relatively straightforward hematomas. Maybe head mal assesses something that really confounds people. So I'm gonna focus the last 20 minutes on this very large area. What you get is a huge topic, his own right to talk about where cells are prematurely destroyed and so hemolysis is just simply the premature destruction of cells on. Do you become anemic when your bone marrow can no longer compensate? So you may have a modest is going on, which is stable, and you may even have normal counts. And you can get these things called intravascular where within the circulation, the cells destroying you just release or their contents. Or you can have increased reticuloendothelial destruction cells may loosely and that's the extra basketball missus. And there's lots of causes like so many. The way that I think about this is to break things down into whether there are things outside the cell that impacting us out and causing a policy is or whether there are things with in the cells that are causing hemolysis. Let's start with the very interesting intrinsic stuff, which red cells don't really have much in them. Apart from hemoglobin, their roles are quite limited. They have gaseous transport, they have not got side and some basic dilation type roles on a few other bits and bobs. But they don't have much in them, so it makes him quite simple. You could have that as a membrane on. There could be things wrong with the membrane. What that normally comes down to is Member is a member of apathy is on the most common one. We may have heard off this ferrocite OSIs, and this is an autosomal dominant things. So 50 50 chance of at me, Parsi onto your Children on. They basically have a A spectrum defect. That means that they don't form the biconcave disk. They just have these big, round red cells, which can still transport him, but they are more subject to destruction early destruction because they can't quite because they're not the right shape they're not malleable on. They gain damaging time, have similar things with a little cytosis on the matter status on a whole bunch of balance. It does, and other members of these. But the HS is the most common one. Um, and they can have all sorts of because if there's something that kicks in that knocks him off their perch, they can certainly enter him about hemolytic crisis or even in a plastic crisis. Where they're they're compensation is no longer happening. They have parvovirus on, but they haven't got enough cells that will survive long enough for them not to become anemic, you know, so they can run the real problems. Then we have the hemoglobin up the so there's something wrong with the hemoglobin within the red cells. Now there are rare hemoglobinopathy defects, which you know is the whole topic, but the ones that you probably heard off our sickle cell disease, which encompasses a range of defects. But they basically have cells palm arise, and that was in fourth and final employees, and they contract the cells and make them all horrible on. They then blow I/O of this one as they're exposed to a hypoxic states. And that leads the early destruction and also very close of crisis as these from Boston through these things clumped together and caused from both sis. Um, then you have fallacy me where you have an absence off hemoglobin production off one chain or another, and that leaves were really variable phenotype with cells that the survivors long but also a really failure of hemoglobin production. And that is a huge spectrum of disease on does come under the hemolytic courses, and then you have the ends of apathy is which basically means the small amount of enzymes within the red cells that maintains the small amount of metabolism is going on. There's any, you know, a few of these Heck, so so shot kind of shuts things that that the ones that will be most prevalent in your mind's from medical school will be stuff like G six PD, which you can set off a oxidated crisis when you're exposed to certain medications or mothballs or father beans on. Do you just don't have enough to keep the cells healthy or you have things like peak a deficiency, which is quite rare but comes up from time to time on. That's a way of thinking about the intrinsic things that can go wrong. And so if you have ah, a young person or somebody's been rejected, then you might start thinking about these as causes off your, um, hemolysis Okay on. Then we have the extremes it causes now, almost always in thing adult population. The most common thing is the fact that these are immune mediated. To some reason, the immune system has been triggered on the immune system has decided that red cells are bad and it's going to destroy them on Do the easy test to go looking for for this one is to look for that by doing a direct anti globin test. This looks for Circulating antibody to see which, which would be acting. It's red cells on. That gives you a good idea off what's going on the nonimmune causes of that negative ones. They're a bit rarer on. Obviously, the intrinsic causes will always be that negative, um, off the immune causes. People get very worried about these things. What on earth is warm What on earth is cold? What on earth is mixed? What on earth is this? It's very weird. What it comes down to is when off those, um, antibodies active, are they active at room temperature at sporty temperature or not On the most common things that I G, which is activity 37 degrees on D, is the most common thing, and that's warm or two immune hemolysis. Okay, the cold tamale assist is where you do it at four degrees on you can quite often gets cold a gluten ins at four degrees, but when you warm the sample up, they start working on, so it doesn't have any clinical impact whatsoever. So the most common thing is that you'll get a sample that clumps together a gluten eights because of these circulating colder glutens. But they don't work at 37 degrees of body temperature, so it doesn't affect the patient to talk this of extra sample, but rarely it can. And if you have cold visions and the main trigger for those people is getting cold, it's much rarer. It's normally compliment mediated thing can happen, but it's very rare. Okay, um, and so the other things that can cause it are things that stuff like drugs, which trick of the immune system of confuse the molecules? Connective tissue disease very commonly stimulates an immune response and getting on topics. The the rheumatological condition is the mainstay of management, and you can also get this with lymphoproliferative diseases because obviously lymphoid cells are the ones that produce antibodies so they can be quite easily trick it toe produce a dysfunctional protein or antibody that will attack the red cells on. Then we start thinking about the nonimmune cools is which going back to the previous stuff, some people like divide things in the extra vascular, which basically means that you've got cells that are, you know, deemed ready for destruction. So stuff like cirrhosis leading to pour membrane for forming hyper Splenda is, um, whether, see explains, is very active on lots of red cells. Go there and they can't escape infections, particularly intra red cell infections. Bartonella babies here both sort of things. They will lead to increased red cell production because your body wants to remove those cells from circulation. There are other extra Mexico's the whole big list. Interesting is a bit more interesting in the sense that there's something within the circulation causing red cell destruction that could be infections can be transfusion, where the antibodies latch on to transfuse cells. PNH snake bite because it copper copper relation with Wilson's. The interesting thing here is a marker heart, a mantra. Angiopathic hemolytic anemia that can come from all sorts of causes from the simplest of being, ah, heart valve, where, as the red cells pass through a metallic valve, most commonly, they just can't survive the process to get shared into pieces. And you end up with hemolysis within the circulation. If you have micro from by down with a very bad level, then you'll start to see a mark. Our pictures. Those fragments go through and they get shredded the rest of get shredded. Buy those trabecular meshwork down that level, so there are many causes down that line off hemolysis, and it's important to get your head around. What's going on now When it comes to Hemolysis, this is just a basic summary, which I'm happy to send out off how to break things down down that line, whether it's intervascular vascular in New Nonimmune, where the um so in the assessment of anemia. The absolute thing I want to really get through is that as ever in medicine, the most important thing is a decent history on de examination, because that will tell you most of what you're going on. What's going on? What symptoms of anemia do they have? Is it fatigue? Breathlessness, even being sinkerball, palpitations, chest pain, breathlessness You may see signs of a molecule with jaundice or regional back pain. Where the kidneys are rechecking that stuff, you may see chronic signs of hemolysis. Where the bile pigment is from bilirubin is is much higher. You see bilirubin pigment stones in Goldstone, which is actually a very common cause of Goldstone's in a young person. If you have an 18 year old who has, you know, Goldstone's causing significant problems thinking about things like human, if it continues because that may well be the cause, the travel history will be important. The history of bleeding, chronic blood losses, menstruals take a good menstrual history, and young women assess those type of things. Examination wise, you'll see the stigmata off, you know, anemia, iron deficiency. You may see neurological signs and beat off or folate you may see signs of anemia in terms of pallor can jump title power, you may see a tachycardia. A flow murmur is very common in anemia, particularly hemoglobin gets below about 70. You may see cardiac failure. It's really pumping hard and can't keep up. Apria Patrick jaundice, meaning that the bilirubin hasn't bean metabolized by the liver enzymes. So you end up with a uncomplicated happier of anemia. You may see Splenomegaly may see this more phys, um, in those rare inherited bone marrow failure syndromes. So although he's things can give you clues about where you're going and going back to Hemolysis, the most important thing that will tell you it's a pollicis is a full blood count on the reticulocyte count. Because if the reticulocyte count is high in the context of anemia on, there's no history of blood loss. You know that that blood is going somewhere and there is something destroying those red cells early because of bone marrow is keeping pace and really working hard and not keeping up. And then you need to evaluate the course, which would be doing your D 80 to try and figure out. Is this immune mediated or non immune mediated the blood film Making you some clues, the ldh will be high. The split bilirubin show that uncomplicated habit of the haptoglobin. This is the molecule in the blood that mops up free hemoglobin, which is causes incredible oxidative stress on the body and can really cause habits. So we have a protection mechanism, but that will get very quickly overwhelmed. And you'll end up with very low haptoglobin because it's all been used up mopping up that free hemoglobin as those him and him on a minute process occurs. This is a the 80 and it just a simple test that basically wash the cells, Put some anti human antigen in on, see if those antibodies are present on the surface of those red cells. And that tells you that you know you've got circulating, um, antibody. Whether that be from the person themselves, which is autoimmune or in babies, you might see aloe immune or in transfusion reactions. You may see a low immune where the antibody has come from someone else, but mom or the dependent. Okay, the blood film can be incredibly useful as a first line test. You can see this shape and size of the red cells. You can see if there's hypochromia and microcytosis, which could be on deficiency or rarely. A thalassemia. You may see sickling. You may see fragments of cells from that mar, huh? You may see malignancy may see cancer cells. You may see Sarah sites from HS or hemolysis. You may see bite cells will tell you this. Oxidated Ramallah's is going on indicative G six PD. Really? You may see signs of stress in the marrow. You may see signs of infection. You can see some of you know, sometimes you can see Dr Cox invading those red cells. You can see ah, huge amount of useful things within the blood film that give you some clue. Is that what's going on? So that's what you'll see. So the first slide, they're looking down a microscope. You can see that there are these cycles off cell where these red cells means have with this slight confirmation, Allchin Angel are open when, in hypoxic states, polarizing all the hemoglobin goes into one long chain rather middle separate on that condenses the cell and keeps it rigid, and it cut and it will not work very well. It will be destroyed earlier on day will cluck together and cause microthrombus eye and can cause basically said prices and things like that. You can see fragments. Which of these things in the middle of the market, which is can be a life threatening indicative, life threatening diagnosis. There should not be best. And you can see signs of lymphoproliferative disorder is with this one, which shows a a clear lymphoma that Maliti, which is a little although I'm looking a long way out, the management of anemia is as per the cause. I do not hold lifesaving transfusion. Um, in the world of transfusion, there's a lot of push to avoid transfusing mostly don't need it. But if you've got someone who's got clear cut signs of, you know, chest pain, you know, Mark breathlessness being very, very poorly and a risk of that being markedly worse. Very, very quickly. Do not what? Withhold lifesaving transfusion, Um, for autoimmune hemolysis, which is one of the hard things and manage you The on auto antibody will latch onto the red cells on the cross match is effectively looking for that, for alloantibody is so it confuses it completely. You have this pan reactive panel where everything, they try and figure out trying to get what what antibodies that person has will be positive on. So you have to wash the cells of that auto antibody to see if there's any significant aloe antibody that would lead to a transfusion reaction and could cause problems. If you're struggling, you're trying to find the best match based on the historical data and what you need for that patient. But so be a B o compatible recent capacity can on K kill matched if you can. You can give steroids to quell the immune the immune system IBIG too much up free antibody plasma exchange to get rid of if you really need to it. And sometimes you might even need to do another. Most expect me to try and stop the spleen, destroying everything to save lives. I wanted to cover very quickly childhood primary, warm autumn in, which is much less common, Um, and normally comes after infection but will be normal self limiting. But it's something quite rare. It's more just to say, think about other causes. That's why this case could be so useful. Um, are finished with 10 minutes left for questions. We've covered a huge topic in a very quick amount of time. What I really want to just holding on is the basics. Take a good history. Take a good examination. Look for signs of occult blood loss. Do your PR do your examination's take a good history of any menstrual bleeding. Any dark stools, Any other signs of anemia? Get the basic tests done. Get the full blood count. Look at the MCV. Think about I and think about B 12 folate. Think about the reticulocyte count. Think about hemolysis in the right context. On if you have that information to hand than your consultation with the hematologist will be 100 times easier because you've got all the stuff away and they have They've got nowhere to hide. They'll have to say right. Okay, next steps also think about family history on consanguineous He in the younger patients for those in inherited bone marrow failure syndrome on have to think about the historical context. Have they ever had normal counts on Is something changed or is this sustained picture Okay, um, off the any questions, that's what you see. Um, George has said, um, yet I'm not the same question That definitely said What? What are you referring to? Because there are, You know, hemolysis could be triggered by almost any drug under the sun. Really? But there are things that are more prone to cause that than other things. Predominantly some antibiotics. There are some chemotherapy agents and particularly monoclonal antibodies coming forward that do that. But actually, there could be idiosyncratic reactions to anything. So quite often will do specific drug related re agents to go from there. But the most common things are some antibiotics and some chemo talking chemotherapy reagents. Okay, Um, have not just young woman deep in your quite right. I meant for me. Young women are premeds, um, menopausal. Um, but Azzan obviously met story. Any menstruating women should have that one. It can be very common in a zoo approach. Menopause changes in menstration can be quite marked. Actually, people can come quite an official quite quickly, so that's a very good point. But in the hematology world, a young woman is anyone under. There's about 60. Is there anything else anyone wanted to clarify? Please, If you want any further references or anything else that you're just not sure about. Please email me more than happy to come back to you and just sort of guide you. As you can imagine, there are so many papers out there, but I can guide you some some things for particular areas of interest if that helps, uh, Louise notice what criteria is followed for blood transfusion of a patient with anemia. That's a very good question. Um, on one, that is very interesting. Actually, it's It could be very hard to identify who should have a transfusion. What we do know is that there is an evolving, um, body off data suggesting that you should only transfuse on a very restrictive basis. So we're increasingly moving threshold based transfusion down to about 70 g per liter from where it was previously 90 to 110 15 years ago. Because we know that long term outcomes, including 30 day mortality on on sort of survival to discharge are much poorer in those who liberally transfused. There's obviously immune disorder elation from having someone else sells transfused into you. Um, there's there are other ways of very deterministic risks that we're aware off stuff like transfusion reactions and blood borne viruses, there seemed there are definitely factors to do with transfusion itself that lead to poor outcomes. So the general cut off is about 70 or if they're significantly symptomatic. So it is very much one case by case basis. And it's also gonna be based on your understanding off what the underlying pathology is because if they're sitting at 80 on, you've identified a clear iron deficiency anemia, and then it got chronic, very slow occult bleeding that you're looking into. You know that if you give them iron a week later, if they haven't had any further blood loss, they're gonna be a 90 a week after that, they're gonna be out 100. So in that circumstance, you wouldn't transfuse thumb, you would give him the treatment. If you've got someone who's got acute leukemia or a bone marrow failure syndrome, you're not expecting that to get better. You're expecting it to get worse. So you might be more inclined to give him a transfusion to stop them becoming symptomatic and aimed for ah, higher transfusion level. The other thing I forgot to mention is if you got a megaloblast IQ anemia on your transfuse him aggressively. So they may come in with a hemoglobin of 30. If you give thumb, you know, transfer them up to 80 which is four units of blood that is more likely to tip them into heart failure on in in a glass chemo. So in that circumstance, you might give them one or two units, then reassess on replace, because actually, within a couple of days, they're gonna be pretty Well, okay, so all of those things come into play on also, what else on the horizon if they need to know. Urgent procedure for a reception of their bowel cancer next week. You may want to talk him up to give them better surgical outcomes. If I am replacement on IV level doesn't work. So it's very patient Pacific. There are thresholds we follow on. Impatient basis. Restrictive strategy seemed to work better. The majority of patients, I hope that makes sense. Um, if on I find normocytic anemia tricky. You know, um, the important thing here is normal. City anemia hides all manner of ills. You might have a mixed efficiency. You might have, um, you know, anemic anemia, chronic disease. You might have other things going on. So with enormous if you need me, you don't have really good clues to say, Go down this line, Go down. That line is obviously a Mexican. You know, you're very quickly saying right on deficiency. Hemoglobinopathy very little else. Macrocytic anemia, right. 12 folate fired function ridiculous. I toast Got say that Actually, ridiculous sites are bigger. So if you have a marked ridiculous cytosis, your MCV will be higher. Which is why in humility anemia, you'll have a raised MCV. It could be very helpful. The same thing happens in disagree for poisons. If you have a bone marrow pathology, you will also end up with a macrocytosis because your bone marrow is struggling to compensate. Okay, but normocytic anemia It's almost always either to do the basics in terms off Understanding, you know, is that iron deficiency. There's something there that hasn't quite lead to enough microcytosis something else, or they compensate enough, do the basics first, and then start thinking about other things, like myeloid screens, my lab screens, thyroid function on looking for other things, but also thinking about that context. Normocytic anemia is most common in people with anemia off chronic disease. They will have kidney impairment. They will have liver impairment. They'll have a rheumatological condition. There will be something in the history that will say, actually all the basic tests and negative, and they've got a clear cut reason for their mild anemia on that's what it is. And so you can quite often but it down to that without to go forward. And then what is the rate at which the hemoglobin increases with each transfusion? So you would expect one unit to increase an adult by about 10 g. Believe so you started 70 and you expect them to get to 80 that in Children and increasingly in adults, and you probably will see this in the next 2 to 3 years. We should probably be transfusing on a weight based thing because a unit off 500 mils will be a very different thing to, ah, 97 year old, 37 kg frail woman. Compared to you know, a 200 kg a man off 45 that blood volume will go very different ways, so it's very patient pendant on ball, so depends on the insulin pathology. If they're hemolyze and it may not last that long, but on the whole one unit, 10 g per liter. Okay, on The important thing now is if they're stable. Because of that disparity, what's sensible is always try and give him one unit. Um, then reassess. It'll blood count so that you have void the second unit. It is not needed because of the poor outcomes, which is a dose dependent relationship. Each unit of blood increases poor outcomes long term. So that's why increasingly patient blood management is important. Okay. Is that anything else? I can clarify that Please do contact me. If there's anything I can help. Hopefully you'll always encounter friendly hemotologists. I will always try their best to help you, but it will be a lot easier if we have this information. Um, Andi, Um please call me if there's anything and help with. All right? Okay. Thanks 0.1. Have a lovely evening, but