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Um Hi there guys. Thank you for joining us for another seminar. Um So today we've got uh hematology special with one of our registrars. Um Puja who's currently um he's currently doing the session first today. Um But she's one of the hematology registrars over at Royal Sorry. Um So we're just kind of go the different presentations. Um And without further do, I'll hand it over to Puja. Thank you. So, thanks for asking me to present today. I'm one of the S T four's on hematology at the moment. Um And I decided to choose this topic. Um It sounds basic, but we're going to kind of break things down and then go into some of the more trickier aspects because I know hematology um instilled fear into people. Uh and often isn't that very well understood. So I'll try and kind of make it more accessible for you. Um And please, I would like this to be interactive. So um please try and ask questions or volunteer if, if you think, you know, um some of the answers to the questions. So, um my presidential today is going to focus on anemia and different, slightly rare types of anemia as well. I'm gonna really focus on the diagnostic aspect. So this isn't going to go through the basic management. I'm sure you're aware of um the acute presentations. This is more looking at how we are investigating it. Um and how we kind of really pin down what's going on with this patient. Okay. So why is this patient anemic? So we're going to do an overview of anemia. I'm gonna go through how to interpret a full blood count with some other parameters. You may not be used, used to using um look at red cell indices and iron studies. And then I focus really today is going to be on human hemolytic anemia and how to approach diagnosing this, what tests we use and what they show and then we'll go through some clinical scenarios to try and um put these into practice and kind of work through what investigations we would do and how we would pin underpin the diagnosis and manage it. Okay. So when we think of anemia, um this is the W H O definition. It's a condition where there is um uh an insufficient number of red cells to meet the body's physiological needs. So that varies um for each patient to patient, um anemia has three different criteria. We think of it as a low hemoglobin, but actually, um you can have all three. So a reduced hematocrit and a reduced red cell count as well. In terms of diagnosis. It varies between different patient populations. So that's slightly lower threshold for women. Um and we have kind of cut offs of less than 130 g per liter for men, 1 20 for non pregnant women. And there's different criteria for um throughout pregnancy. So as you progress through pregnancy, um the actual diagnostic thresholds drop and for pediatrics, it's very specific to the age and the gender of the child. Um So we don't have one set cut off for pediatrics. Okay. So this is probably the what you're used to classifying anemia um with previously. So we look at the MCV, the mean called muscular volume or mean cell volume, essentially fancy words to say the size of the red cell. Um Could anyone sort of volunteer some of the the causes of a low MCV? And generally this is kind of less than 80 we'll see if this chats working. So what do you use your causes? Um uh I think uh the slides don't seem to, to be keeping up with. Uh it's a they, they don't seem to be moving on on. Can you see what slide are you on? It's just, it's the first one. Okay. Let me just uh can you see it now? I can't see any. No, you can. Uh So them even now. Okay. Can I just go back a sec? Can you see that? Uh I didn't do it back at that time. We're on the classification mean capacity killer volume, you can see that okay. Can you see the causes or uh we can, we can see the cause is um okay, it doesn't seem to be telling up annoyingly okay. So anyway, um so you can see the cause of that. So we break it down. Usually for low MCV, usually the most common cause is being an iron deficiency. The other one to think about is a haemoglobinopathy, um particularly if the MCV is very low and out of proportion to the hemoglobin. And then you've got the rare causes that some of you may come across when you're doing kind of paces and um you're part one exams. Um The classic one, they always bring up his lead poisoning although I've never seen it and then sideroblastic anemia and other types of bone marrow failure, but generally a low MCV tends to indicate an iron deficiency or hemoglobinopathy. Your normal M cvs tend to be more things of anemia of chronic disease. So, chronic kidney disease, heart failure, inflammatory and autoimmune conditions, chronic infection. And then in terms of hematological causes, you can have multiple myeloma that presents either as a normal normocytic or a macrocytic anemia. And pregnancy also has similar changes when uh to the red cells as well. So you can have enormous citic or a macrocytic picture there. And then we have to be mindful that you can get a mixed hematinic deficiency. So if you've got something that's increasing your red cell size and some thing that's decreasing, it, actually, your mean cell volume could appear normal even though there's two underlying dual pathologies going on. And then for macrocytic causes, um, the really common ones are alcohol. So, always ask for alcohol history. Um, and if you have to be a liver disease that can also present like that B 12 and FOLATE is a classic and easy way of um easy test to kind of diagnose and then you have hypothyroidism and there are certain medications that can cause it. So we'll go through that in a second. Um But if you have an anemia and a persistent macro cytosis, you might start thinking about hematological causes. So one would be myelodysplasia. So one in your older adults on another is multiple myeloma. Okay. And for or in terms of the treatments, one of them is hydroxy karma that we use for mds and that itself can cause a raised MCV as well. So there's lots of different things. It's not just um, the basic. So if there isn't a clear cause, um, you know, we can kind of categorize it in this way, but there are other ways um to look into anemia's as well and just remember that there's always a secondary cause anemia just doesn't happen on its own. Um So it is good to look at the underlying reason why to try and correct it and make the patient feel better. Can you see this slide? The next one? Um, no, it's not going, I'm going through the next one. I stopped caring and try again. Uh, I'll come out of it. Can you see them when it's on my? Yeah, I can see the mouth moving now. Okay. Is that when you're cooking the fly church? Was that? Yeah, it's a bit bizarre. Now, can you see it? Uh. Yeah. Okay. Well, you just tell me if it disappears, I will do. Okay. Um, fine. And I thought anything, I'm just at the moment, but usually we use the hemoglobin. We're used to using that. And that's literally the protein that carries the blood cells. So that's the parameter that we always use. But lots of these other ones can be really helpful. Um, but it's not very well understood. So the hama to quit, um is quite, is quite useful. We use it in polycythemia. So when you've got too many red cells, but also, like I mentioned earlier, the definition of anemia, you have a low hematocrit. So that's the percentage of the blood that's made up of red cells. So I've got a picture in a moment but when you collect your blood cells and that your blood sample and you spin it, it gets separated into it's plasma. Um and the actual red blood cells at the bottom. And that's the little part that we uh define as a percentage the red cell volume So in anemia, you've got less red cells and the policy theme is the opposite. So you'll have a high hematocrit and the red cell count will also be low in anemia. But often we don't really use that. We've already mentioned the MCV, which helps with diagnosis, but like I mentioned, you can get deal pathologies. So really, that's when you have to use these other parameters. So another one that looks at the different sizes is the R D W, the red cell distribution width. And it essentially assesses the range from the smallest red cell that's there to the largest. So in iron deficiency, you have a big range. Um and actually a high R D W indicates um iron deficiency. So if you have a mixed deficiency picture and a normal MCV, but a really high R D W that can still kind of suggest iron deficiency. And then we've got a few other parameters that I think by the time we're looking down on a full blood count, people start ignoring these ones. Um But again, very useful particularly for the fallacy mia's. So an MCH is a mean cell hemoglobin amount of hemoglobin in the red cell. And it's very low in thalassemia and much lower than in iron deficiency, but still decreased in both. And it's very similar to the mean cell hemoglobin concentration, which again is low in both and the new kind of parameter that's starting to come out on our blood counts is the percentage of HRC or the hipaa chromic sells. This is referring to the color of the cells. And we know that in iron deficiency, you get micro citic hipaa chromic. So you're lacking um that color. And so you've got a higher proportion of that in iron deficiency anemia. And so that percentage would be high. Um Now, I can't see the bottom of screen there, but the reticular site count will go into in a little bit more detail. And that essentially a marker of how immature the red cells are. And we can use that to see if your boma is actually producing red cells in response to anemia. Okay. So hopefully you can see that slide and that's just a diagrammatic way of ducks much by the. Okay. What I'll do if you can see it like that, maybe I'll just carry on like this. Yeah. Okay. Should I just carry on like this then? Sure. Okay. So like I mentioned, this is what happens when you, when in the lab, the lab spin the blood down and separated into its components. So with your anemic, you have low percentage of red cells and policy eigthy Mick, you've got a very high humidity, quit there. Okay. So we've classified it now, but what's actually going on, what's causing the anemia. So if you think of it in basic terms either and not enough is being produced. So there's a marrow problem or something that combines with the red cells to produce, proper, to produce them or it's ineffective. So something like thalassemia, you've got a mutated globin gene and it's not working properly. So you'll still produce the red cells. They just don't work very well. And last of all is you're producing the red cells, but they're being broken down faster than they're being produced or they're being lost, for example, in gi bleeding, okay. Um in terms of this pathway, um when you have an anemia, your kidneys are stimulated to produce a referral poet in. So that's where the word comes from. For erythropoiesis iss. So if you have an anemia or things like hypoxia, it stimulates your kidneys to produce this hormone and then it's a feedback cycle. So it will go, it will stimulate your bone marrow to produce more. And what you produce are the reticulocytes, the immature red cells and they take about 24 hours to mature. So when you have a high reticular site count, you know that there's lots of immature red cells in the bloodstream. So it's, they've been churned out for a reason and that's usually in a response to an anemia. Okay. There's some disorders where you have to kind of um tumor's on the kidney that can produce with reporting and dr uh this cycle to to continue. And that's one of the causes of the opposite problem, which is polycythemia. Uh and again, hypoxia from COPD and various other respiratory causes can, can cause that drive as well to make the opposite problem. So basically, are you not producing your red cells? Are, are they ineffective or are they being broken down or lost? Okay. So, um we're going into the reticular site count. So we don't often in medicine use this market, but it's actually really helpful in helping to differentiate. So shame we don't do it automatically when you're doing a full blood count really. But anything that's indicating that the marrow isn't producing the red cell. So a production problem, you tend to have a low reticulocyte count. So your marrow is not making these immature red cells okay. Um with anemia of chronic disease and some of the fallacy mia's, there's a functional problem. So you're still producing your red cells. Um but they're not kind of, they're not doing what they'd like to. And you can get this functional iron deficiency anemia with anemia of chronic disease. So the one I will focus on a bit later is hemolysis iss. So you'd have a high reticulocyte count usually in conjunction with anemia and there's lots of different causes of that which we will go into. But a reticular site count can also be really helpful to see if your treatment's working. So for example, if you have a severe B 12 deficiency, it may be that you don't produce um you don't produce enough red cells. So you're anemic and then when you start producing them, you can get a, a ridiculous cytosis. But then when you're completely replete, um in response to anemia, your reticulocyte count goes up until it's normal. So it's a normal response and it really is quite helpful um when you're trying to work out what's going on and I know that you're probably used to these causes. Um and looking at a ferritin and deciding what type of anemia you have, but there is more to anemia than an MCV and offered him. But we've done lots of research now into these functional iron deficiencies. So we know that less than 15 micrograms um confirms the diagnosis of iron deficiency anemia, but you still can have iron deficiency with normal ferritin levels. And that's in the context of a race CRP and chronic inflammation that stimulates helps it in that um causes this, this kind of functional impairment if you will. So you would target people with chronic kidney disease and heart failure and potentially give them parental lines or IV I and when you need to. Okay. And last part of the kind of the blood cell parameters. So we've already mentioned ferritin and that's the actual protein, the iron that's bound to the protein. But we know it's going to be altered by infection and inflammation. Serum eye on is one of the tests that is analyzed, but it's not very useful at all in that it changes from day to day and it's kind of a an indication of the last meal that you've had. So it's not of any really clinical significance except for we use it in this ratio that I'll mention in a second. And then the total iron binding capacity is the ability of the blood to bind um iron. So if you are anemic, your body wants more iron and actually you've got a high binding capacity. So you try and hold on to that iron. Um So in iron deficiency and um you try and hold on to it. But in iron overload, um hemochromotosis, it's the opposite, you'll have a high tea, you have a low TIBC because you've got too much iron. You don't want any more to be stored. And then with transferring saturation, I find these really useful, particularly for the anemia of chronic disease. Patient's with a high CRP and the B S H suggests that 16% or less than 16% still suggests I'm decrease the anemia. So if you're still clearing it, um I would do iron studies as well as a ferritin, particularly in the context of other um things going on. Now, I don't know if there's any questions at the moment. I can't see any on there. So those are the basics and I know a lot of you would have known um some of those already, but hopefully just looking at the other parts of the full blood count and trying to interpret that as well. To see what's really going on. So I just move on to the next part, which is hemolytic anemia. Okay. So that's the premature destruction of red blood cells. Now, it's normal lifespan of red blood cell is 100 and 20 days and normally after the 120 days, it's broken down in the reticular endothelial system. So that's your liver, your spleen and the macrophages, the white cells that kind of phagocyte toes and breakdown or the red blood cells. When you have a hemolytic anemia, the destruction is much greater than the production. Okay. So I'm just going to ask a few questions now. So how can someone present with a hemolytic anemia? Are we able to respond on the chat if possible? Two? Okay. So I'm not sure if that's working for me, but there's lots of different presentations. So it's a wide variety and it can just be normal features of anemia. So, pallor lethargy, breathlessness and there's also more kind of worrying features. So jaundice, pata, splenomegaly, dark urine fevers, um sometimes gallstones. So those on those of you on surgery should have, I think um wisest patient getting recurrent um colecystitis. Is there an underlying reason? Um, patient's with sickle cell anemia or kind of hereditary causes of demolished sis often have recurrent gallstones and finally have acrocyanosis or Raynauds. And and this is essentially where the red blood cells in your fingers start breaking down usually in response to the cold weather or other triggers. Um But any features like this, it would be worth thing him honesty screen and we'll go through what those entail. So how do we break down how to manage hemolytic anemia? There are so many causes as you can see. And a lot of them are quite rare and it's quite a complex topic. So I'm just again trying to break it down into an easier way um of understanding it. So my first question is, is it intravascular or extravascular hemolysis? Iss now, I mentioned that it's normal for the red blood cells to be broken down by the extra vascular system. Um But in pathological causes, you can get intravascular hemolysis generally. Um This happens um when this happens, the patient's are much sicker, but there are cases of either um that overlap. So, actually vascular, we mentioned which organs were involved. So we've got the spleen um and the liver and that's when you get a raised bilirubin, particularly unconscious gated. And when that goes to through the to the gut, you get Sterk oh Bellingen. So that's when you're getting your dark year and um pale stall. So it's the red blood cells are being hemolyze and it's going via this aria system. In intervascular Hamal icis, the red cells are being broken down within the blood vessels, it releases free hemoglobin into the circulation. And that can be quite toxic. And one thing I just want to differentiate here is we think sometimes that hematuria indicates him on icis. But actually, hematuria is the full red blood cell. What we worry about is hemoglobin urea. So when the red cells actually broken down and the hemoglobin protein is being excreted in the kidney and that can be looked for and you can test it on a urine dip, but you need to send it for microscopy. And also you can do something called um hemosiderin uh test to see if there is chronic hemolysis iss so slightly different presentations depending on whether it's intravascular or extravascular. So again, if you, if we are able to interact to just kind of go through what a basic hemolysis screen might look like. What sort of tests could we suggest anyone? Any ideas? Okay. So we have different ones again, depending on whether you're targeting intravascular or extravascular hemolysis iss the basic ones in both that are increased are your reticular sites. We already mentioned that. So in response to anemia is going to be producing these immature red cells, the unconscious gated bilirubin, although it's mostly with extravascular, you can get um intravascular causes doing that as well. And then an LDH, so that's one of the enzymes, there's lots present on red blood cells. So essentially that is a marker of Hamal ESIs, but it's really nonspecific. So, you know, it's raising infections and and all sorts. So we can't kind of rely on that. Um a blood film, sorry, this is American. The blood film is quite helpful in determining which type of Hamal icis. It is um the worrying things we want to look out for are schistocytes or red cell fragments. So, um if you're worried at all about him, all icis doing a blood film and alerting the, the lab or the hematologist about it because this is mostly an emergency and we'll go through that shortly and a blood film can also show other causes of hemolysis. So sparrow sites, um it's something that we can, we can pick up and that can be useful. We report the film. So if you see that there's a mention of parasites, that's just something to think about. And then another one that we, we send just away at Royal Surrey. But another test that we can use is called the haptoglobin. So you might, we probably hear all these words that we use and not really understand why we're we suggest it. But the haptoglobin czar proteins that are circulating and they help to mop up any free hemoglobin. So if you have your red cells being broken down here, hemoglobin on its own is actually quite toxic. So these haptoglobin mop up the excess hemoglobin in Hamal icis and because they're bound to it, they are reduced. Okay. So generally you'll have a hieratic count, high bilirubin LDH, but a low haptoglobin, okay. It's worse in intervascular, but it can, it can extravascular hemolysis as well. And then the more worrying causes of intravascular hemolysis, you'll get hemoglobinuria. Um and you can even get things like met hemoglobinuria and things like that. Okay. So we've established whether we think this might be intra or extravascular. So the next step is whether it's immune or nonimmune, anybody know what causes or how we differentiate between the two. So this is where the D A T comes in. So the direct antiglobulin test, this helps to see what is whether this is an immune hemolysis or not. And we can decide what is coating the red cells. So in the lab, they take the sample, they wash it and then they add a re agent that binds to any of the antibodies and they see if they stick together and they cause an igloo tenation. So what do we mean by a positive D 80? So when you first have a D 80 there are two antibodies that the lab tests and I G and A C three D. So this is an immunoglobulin and this is part of the complement cascade. So they test for both. If that's negative, it's really unlikely that this is an immune humility anemia. So you want to go down and look at other causes more structural things, for example. But if you have a positive D 80 there are antibodies there, one of these antibodies is positive and you want to find out which one. So you then do um on a specific deity and the lab generally do that themselves without having to be asked. Okay. Um And they will kind of grade how strongly they react. So, back in med school, you might vaguely remember these terms. Um But essentially the I G that is usually involved in extravascular hemolysis iss, if the I G is positive, then we can term this a warm or two immune hemolytic anemia, sometimes that is positive in conjunction with this C three D but on its own, it's suggestive of a warm huma lytic anemia. And how do I remember it? Usually, I think of C three D is a cold huma huma lytic anemia. And that's the only one that causes both intravascular and extravascular. So essentially you do the D 80 you find out which antibody is positive and how strongly positive and then you kind of use these test to see. Do we think this is a cold glue tenation which has a different management pathway to a warm one. But we, as your hematology team will be guiding you through all of this. So even just getting to doing the D 80 would be very helpful and getting you on your way. So how do we differentiate the immune causes? So your D O T is positive, what does that mean? So you either have a low immune or autoimmune. So whenever we use the word a low immune, that means that there's an antibody from a foreign antigen. So, an antibodies produced to this foreign androgen. So for example, your, you've received blood from a donor and they're a be incompatible with your own blood. Or pregnant women have a baby who has the antibodies from their father, who they interact and cause hemolytic disease of the newborn. And that can be quite um critical and it can't even be fatal at times. And then autoimmune is the body reacting to its own antigens. So, we've already mentioned autoimmune hemolytic anemia, medications can trigger that. Um And in Children, you get something quite rare called paroxysmal cold hemoglobin area. But that's very rare and we don't see it too often. Okay. So we mentioned that we use these antibodies to kind of guide us and we're not expecting you to learn any of these. It's just to kind of trigger your thought processes if, if it's positive, there are idiopathic causes, but the warm hemolytic anemia are usually a secondary anemia to something else. And cancer particularly CLL and and very, very commonly uh lead to a warm huma lytic anemia, autoimmune conditions like sle um and also very common drugs that you may not think of. So if you've got an I D G positive and see three D positive humanistic anemia, your patient's HB is dropping, you have no idea why going through the drug chart and just seeing has anything started and looking at the time frame just before this Hamal icis has happened Um, so yeah, like imagine simple antibiotics. Keflex points. We do use that frequently, eh, nsaids. Um, just have a think is there, is there a drug that's contributing to this for the cold hemoglobin, hemorrhagic anemia's infection is often a trigger. So, EBV and then mycoplasma but if it's primary, so if it just happens on its own, sometimes we call that cold agglutinin disease and these cases really do benefit from, from some preventative methods. So I'll talk a little about that later, but the hemolysis occurs when the patient is cold. So trying to keep them warm and warm fluids, etcetera can help prevent them humanizing and against drugs that we use fairly frequently can trigger this type of Hamal icis as well. And lymphoma can cause both but generally, um it's more of a warm phenomenon. Okay. So we've established um some parameters we've, when we've done the dat dat is now negative. So how that helps is that we need to go down a different pathway and we need to think of inherited causes or something that's acquired, there's no immune element to this. So that's when we're looking into other drugs. So this might be confusing because we've just done, we've just said that drugs cause warm and called him a globe hemolytic anemia, but they also cause nonimmune ones. So ones where your d 80 is still negative. The ones I want to focus on here is the inherited hemoglobinopathy. He's so things like sickle cell and thalassaemia and hereditary spherocytosis iss and then we'll get into kind of the G six PD um deficiency. The enzyme deficiencies which actually occur more often than you might think. So, infections um on, on microscopy, we can see things like malaria, clostridium. These can cause humility. Anemia's um mechanical causes include things like TTP where um you get platelet aggregation and clot formation and that kind of causes trauma to the vessels. Um And that is one of the severe causes of humility anemia and this is a life threatening emergency. So all of these nonimmune causes, I'd recommend doing a blood film because it really is helpful to help to clinch the diagnosis. Um And this is when we're looking for these worrying fragments or schistocytes. So these are what they look like under the microscope. Um and they present with low platelets um and all those intravascular symptoms and um and uh really this is an emergency and a whole talk within itself. So other patient's that are at risk of having Hamal icis. So cardiac patient's who are having um who have heart valves, chaotic stenosis where there's narrowing that can actually cause more sheer stress, pregnant women, there's lots of different um pathologies. So help syndrome of preeclampsia D I C. These can all lead to him all ESIs in terms of the actual structure of the red cells. Um I was hoping to make this bit a little bit more interruptive, but the film here, you can identify the different shapes. So um I don't know if you can see the slide here, but we've got the sickle cells there. Um And these bigger more purple cells are reticular sites. So, polychromasia. So we can see them on the film and we can see under the microscope, Marcus of hemolysis for hereditary spherocytosis, you have these round and dark red blood cells here. So they hide per chromic. So they have, they are the opposite of these hipaa chromic iron deficient um cells, they are humanizing. Okay. So this patient has a structural cause for their anemia and similar to HS you have these are Ellipta site, um sales as well. Thalassemia can actually cause quite marked changes on the blood film. And we mentioned already the microcystic picture which is much lower generally um than you might see in iron deficiency. So you might have an H B of 105 but actually the MCV is 65. And here there's hardly any color of these cells. They're tiny, they're, they're all very ineffective. Um So they can um struggle with anemia. So we mentioned enzyme deficiency. So G six PD, we use that, we test for that on hematology quite a fair bit as there are a few drugs that we use regularly that cause um hemolysis. And so we have to pre empt that and um test for that before starting medications. Um You have infections that can trigger it. And then we mentioned drugs again, they're really simple um causes that might be missed. So again, just go back and look at the drug chart. Why did this person start humanizing? Is there something that can stop? And usually the hemolysis stops as soon as the offending drug is stopped? Okay. So, um we'll see if this is going to work. Um Can you see that slide? I'm on the oxidative slide. Okay. So you can't do the case. Um Sorry, it's got the answers. That's the problem. Okay. Um So just going through the case, um we have a 25 year old female of West African descent with breakfast, this and jaundice. So there's a raise, the H B is obviously very low at 60 MCV is reasonable. Um Billy's high reticular sites, count's a little up and then LDH is very high. So normally, um when you see this sort of picture, I think most people will jump to thinking about sickle cell. Um and the dat is helpful in this case, it's a structural cause it's not an immune course. So that will be negative. And if we do a film, it might show some of these classic characteristic features of sickle cell disease and it would prompt us to do hemoglobin electrophoresis or other sort of uh studies to look for sickle cells if the patient is not known to have sickle cell anemia. So we've mentioned it was nonimmune the extravascular part of it is that the bilirubin has raised. Um the LDH is high. Um Sometimes they present with a bit of jaundice. A lot of them have abdominal pain. Um But there are additional things we need to think about in the sickle cell. Um A namely the test that we do can help guide us. So if the same patient had a D 80 and it was positive, then it would be important to make sure we rule out a immune cause of hemolysis in a sickle cell patient, which is a previous transfusion. So these patient's often present with acute um transfusion reactions. So they may, it may have been a recent one few hours ago, but it can actually cause hemolysis iss for days prior to presentation. So they may have had it a week ago. So it's always important to ask sickle cell patients'. When did they have their less um transfusion and see if that correlates with when they started feeling unwell, they produce lots of different antibodies um and when they receive, but they also tend to make new antibodies as well. And so that's another thing to, to think about. Okay. So second case, um we've got a lady with COPD and breathlessness um with peripheral cyanosis and dark urine. So some of these getting to some of those um intravascular symptoms that we mentioned the dark urine, if they mentioned dark brown or black, that really is suggestive of hemoglobinuria and then peripheral cyanosis or delving into it a bit more. It could even have acrocyanosis iss, it can be bad enough to cause digital ischemia or ulceration. So, when we go through our different investigations, we know that there's an anemia, slightly macrocytic. Um because uh you have a reticular cytosis because that's the one of the commonest causes of humanistic anemia. So this has a very high LDH of 1100 it's that positive. And it's see three D. So see, for cold, there's no I G positivity in this case. So this is very suggestive of a cold humility anemia. And in a primary case, this is likely to be cold agglutinin disease. Okay. So you see those farah sites, you can get some markers of intravascular hemolysis as well. Um But these are the ones that you really need to try and um warn about keeping warm. So ensuring they wear gloves in the winter when we give any sort of blood products or fluid, you can put them through a warmer and that helps um prevent further Hamal icis, especially if you think we're putting a cold blood product into someone. It's going to cause widespread intravascular hemolysis iss. Um So we try and warm them up when we can and because the red cells are breaking down so much, they need more folic acid to help produce um functioning red cells. So they would always be on a supplement, even when they're not humanizing. Uh these patient center have chronic hemolysis iss. Um So if they have a history of it, uh they may have worsening symptoms when they have an infection or if it's particularly cold. So we tend to treat that with Taksim A but steroids aren't um as effective in this scenario. Okay. So if we had the same lady in the same case, but instead of it being see three D positive alone, there was an additional I G element that would suggest a warm hemolytic anemia. So the same case can sort of change your um thought process and we'd look into secondary causes and for the warm cases, you'd actually look for an underlying malignancy. You think about doing a CT scan to see if there's something that's triggering this off. And again, some of them management is similar and supportive with folic acid, but steroids are generally very, very effective and we use them very often and may not need to use anything else following that. Um But some people will require other immune suppression or chemotherapy and treatment of the underlying condition can actually improve the anemia. I think this is a final case. Um So if you have a young patient uh with jaundice and abdominal pain following a recent holiday, um this patient is anemic as you expect, all of them are um with a mild LDH know the ridiculous site count is actually normal that that's negative as you would expect because it's a non immune cause of hemolysis iss. And on the film, there's some sparrow sites and some polychromasia. So this would be a case of hereditary spherocytosis iss. So a structural cause. But if um you think carefully about this lady, she's from Cyprus, so they have her ethnicity suggests that there could be other things at play. So G six PD deficiency is common in the Mediterranean and West Africa. Um she's been on holiday. You need to think outside the box. Could this be something that she's acquired? Example, malaria? Has she been taking any medications? Antibiotics? Anything like that? There's a widespread um spectrum. I'll quickly talk about hereditary spherocytosis. We mentioned that gallstones can occur in hemolytic anemia in about 50% of patient's with H S. Do you have a current gallstones? So, something to think about if you've um seeing them coming in regularly that have a big spleen. Um And like many of these patient's who with hemolytic anemia, if they get an acquired Parvovirus, they can actually go into a, a plastic crisis where they don't produce any red cells at all. And that can be quite dangerous. Again, we like most cause of hemolysis, we'd give folic acid. Um Sorry. Um Okay. And we used to do it more from not so much. Now, a splenetic, a splenectomy can actually curative. So if you take the same case again and say that the deity was positive, you'd look into more immune causes for a young female. Think about autoimmune causes infection E B V. So the clinical history and the test really do help change which direction we go into. Okay. So I'm just gonna summarize now. So hopefully you've got a few more tools to help you diagnose anemia. So instead of just looking at the MCV, maybe thinking about the R D W and using um your basic um iron studies and red cell indices to help guide you in your diagnosis. Um Hopefully, you've got a bit of an overview of different types of hemolytic anemia and how to approach it. It is quite complex. Um So just pick up the phone if you, if you're concerned about this patient with a low hemoglobin, you're not sure what's going on and the labs kind of called you and said they've got positive antibodies, we can help try and source you some blood if you need. Um And there's different ways of escalating that to the blood transfusion service. Um And we can help you interpret a positive D 80 test and whether it's significant or not. Um And I'd always do a blood film if you suspect pollicis. These are a few useful resources. Um uh I don't know if any of you are interested in hematology. Um But lots of the guidelines, the gastro guidelines are actually some of the best for iron deficiency. There's loads of hematology guidelines. Um And for any of you budding hematologists. Um I always talk about him base is a really great website um done by trainees, but simple ways of um giving you information about things that you don't get taught very often. I don't think you mentality thought. Um It's very well at times. So that kind of helps break down um different aspects of hematology. So I hope you have found that useful. Um And if you do have any questions at all, please feel free to share them in the chat or um I'm sure you all know how to bleep or call your um hume Atala gist, but we're more than happy to answer questions about uh hemolytic anemia or anemia's in general. Um So thank you very much. Um And yeah, thank you for letting me speak today. Thank you. I think we sorry. Uh uh Is Doctor Marilyn? I think my wishes kind of echoing a little bit. Uh Okay. Uh We've got it. We've got one question from someone. Um uh they're asking in malignancy where we have changed in a total iron binding capacity on the type. So again, it depends. So if you, it really depends on the type of malignancy. If you, for example, have a G I malignancy, you're likely to have a conquer Rinty iron deficiency. So you would have a high TIBC, I wouldn't use TIBC in your day to day in general. Um And with malignancy, it gets really difficult again, they probably got a high CRP. I would use a transferring saturation instead of the TIBC. It's just if you have a low transferring and a high TIBC that gives you a bit more information. So, um I think it's likely that it will be more because of the, a concurrent iron deficiency rather than the malignancy itself. Any other questions? No. Yeah, I do. Ok. Well, hope you all have a nice evening. Sorry about all the technical problems. Uh There's another, there's another question uh They're asking when is the optimal time to reject HB of the iron transfusion? So um iron actually, I'm I'm sorry, I an infusion or iron tablet, bone replacement. Okay. So um parental iron takes usually a couple of weeks for it to start working, but it can take, it can have an effect for about 4 to 6 weeks if you're looking for an H B trick. Um Generally we'd say about at least six weeks to see the full effect. Um If you're giving parental iron though, we would always give two doses. So I know we always, we often not ambulate these patient's and do it on a day unit, but you would give the first dose and then a week later give the second dose. You wouldn't need to some trust, want you to recheck the HB at that stage, but you need to give the full dose is regardless of what the hemoglobin is. Um But yes, usually I would say at least six weeks. Um but 6 to 8 weeks will be most useful um but much quicker than or align, which is at least three months. Thank you anymore. Did you think the already knows? Okay, perfect. Well, I hope you all have a lovely evening. Thank you for listening and yeah, please feel free to get in touch with any of you want any more you experience or um interested at all in what that entails? Okay, thank you. Thank you. Thank you. Bye bye. Uh ok. Please fill out the feedback form it really have for us in Puja as well. Um uh Thank you so much for attending. Yeah.