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I'll go on mute now. That's good. So let me just make sure that it's recording properly. Hello? Can you hear me? Yes, we can. Hi, Hannah. Yes, we can. Yeah. It says I can't start my video because the host has stopped. Uh, stopped it, but I'm not sure what that means. I never had this before. That's okay. We'll promote, you know, and hopefully should Oh, thank you. Okay, try now. Okay. I'll get it there. Yeah, Perfect. Thank you. We'll just give it a few minutes Where? Wait till everyone comes in. Fine. Yeah. We'll give it a minute or two and then start, shall we? Okay. Whenever you're ready. Hannah, you're good to go. Okay. So, um hi, everyone. I'm Hannah. Gina. I'm a Cardiff medic. Um, and I finished my fourth year, and now I'm integrating, um, in hematology at Imperial. Um, and welcome to the ace it Medical revision session on hematology. And hopefully this will prepare you for your progress tests than any hematology questions that come up. Okay, so today, we'll go through hematological malignancies, uh, anemia, leading disorders and red cell disorders. I'll try and do everything within an hour and 15 and have some time for questions at the end. Um, and also, um, at the end, You can also email me if you have any further questions before your progress test. Um, but yes, let's start with hematological malignancies and, well, first start off by briefly looking at the blood cell lineage, so we at least you know where these cancers are coming from. So this diagram assuring us the different blood cells where they come from but also their location. So let's first start off by looking at the two lineages So you can think about, um, cancers arising from either than my lawyer lineage, which becomes red cells, your platelets and your other white cells, like neutral, fails, basal fails is on a feels that you see in your full blood count. So that's one side. And then we have the other side, the lymphoid lineage, and we get the cells that were familiar with these B cells and these T cells that are involved in our adaptive immune response. And we can just think about the blood cell lineage in those two ways the myeloid side and the lymphoid side. Uh, we can also think about immature cells or blast cells. And these come from the burn marrow and the more mature cell that you see on your full blood count which marrow in your blood and some of them are in your tissues. So just, uh, just so we know what we are dealing with when we talk about cancers. Okay, So when we come to talk about cancers, um, we have acute leukemias and chronic leukemias. There are other cancers, and I'll talk about them a bit later. But leukemia just means cancer of the white blood cells. Um, and we have different types that you have acute and acute. Sounds like what it means. It's quite aggressive. It progresses quite rapidly. It can be quite face like presentation, and usually we're talking about the more immature cells or the blast cells that live in your bone marrow. And then we have chronically teen years, which are usually more slowly progressing, insidious, um, indolent. And these usually affect more mature cells of your blood. Um, cell lineages. So acute leukemia is quite fatal, quite rapid, quite aggressive and chronic. Um, it's more slow growing, and the problem with having acute leukemia or chronic leukemia is that we have growth of one abnormal cancer cell in your bone marrow and your blood. Um, this can fill up your bone marrow and suppress the production of other cells. The good, normal cells like your, uh, blood cells. Your platelets, Your white blood cells are good and do do its job. So we get bone marrow failure. And then patient's usually die from having bone marrow failure and having severe infections because they're not producing any good cells. Um, so hopefully that will just give you some good understanding of what we talk about when we think about cancers. So and that's another diagram to show you where the cancers are coming from or the cells of origin. So, um, loosely we have, um the A m l acute myeloid leukemia coming from the more immature cells in the myeloid lineage. So you're my lord progenitor cell and your myeloblast. Then we have a l l coming from your immature lymphoid cells. Let me have CML coming from your more mature my lord cells and cll coming from your more mature lymphoid cells. So we have cancer on the mild side for million food side acute leukemias and chronic leukemias. Um, so hopefully that will just give you some understanding of what we mean. So let's start talking about the conditions. Um, so I'm going to try and see if we can look at the chat. But my first question, uh, feel free to interact and put things into the chat. But when patient's have acute myeloid leukemia, how do you think they might typically present, um, to, you know, And if one a doctor, how would you? What would they present with what kind of symptoms? Um, let's see if we can look at the chart. Everyone wants to put an answer in the chart. Just give it a go. If anyone wants to a mute themselves as well and make sure if you can do that, I think they're saying the chat is disabled to just find out what's going on now. Okay, it's fine. That's fine. So just spend a few more minutes or a few more seconds thinking about how they might present um, maybe about the kind of patient of the demographics. How old would they be? Um, I should be able to chat. Now, if you guys just have a go Oh, yes. There we go. To fatigue. Children. Okay. Bruising. Yes. Dumbbell. Cytopenia. Yes. Infections. Bruising sepsis. Good. Mainly adults. Yes. OK, so really good answers. More adults over 65. Okay, good. So yes, Um, some really good answers. So we talk about acute myeloid leukemia. We talk about people who are a bit older. So usually over 75 for acute myeloid leukemias. Um, there's another type of acute leukemia that affects Children, and that's the acute lymphoblastic leukemia. But cute myeloid leukemia affects older people, and they present with symptoms of anemia. So you have shortness of breath fatigue that can be quite pale. We present with symptoms of they present with symptoms linking too low neutrophils. So, um, they'll have infections, recurrent infections and then low platelets. They'll present with symptoms of having thrombocytopenia so bruising, bleeding. And also, if you think about where the cancer is coming from. So it's coming from your kind of immature cells of the middle lineage in your bone marrow. So we're going to have some bone pain because your bone marrow is working quite hard and this disease going on there, and then we have something called constitutional symptoms, which basically just means fever. Night sweats, all those symptoms that you think about when you think about malignancy or systemic disease. Okay, So good. Um, and then this picture on the right, we can see gum infiltration. So, technically in myeloma or not, myeloma. Acute myeloid leukemia. Sorry. There are seven types. M one to m seven. Um, and they all present very similarly. So it's not really that important for progress tests. Um, but just to know that with one type of leukemia A m l m five, the particular cell effector So the particular immature myeloid cell, um, infiltrates the gums, you get gum infiltration. So that's one finding that you can have in keep my leukemia. That's quite specific. Um, and then also, pictures might present with the history of exposure to certain risk factors. So older age is that basically the biggest risk factor. But can anyone think of any other, um, risk factors to 4 a.m. L my b t o. It's in response to that question about constitutional symptoms. It's very similar to be symptoms. You can kind of use the terms, um, interchange and being away. But I think b symptoms is more specific when you think about, like, lymphomas and stuff. But yeah, basically the same thing. Fever and might sweat. Okay, so for exposure to risk factors, Down syndrome, Yes. Radiation exposure. Yes. Okay. So with exposure to risk factors, um, there are some good answers in the chat. So mainly we're thinking about exposure to ionizing radiation, Benzie and Down Syndrome and other congenital disorders. Um, become risk factors, um, but very specifically down syndrome for aml and then having myelodysplastic syndrome, which is kind of a precursor. Awful AML, um, increases your risk. So, uh, MGs you do have some blasts in your bone marrow, but not enough to be considered a ml and then certain treatment. So, um, when we think about specific treatments are linked to the development of a ML we're thinking about alkylating. Agents or topper are summarized two inhibitors. Um, and those two drugs are chemotherapy drugs used to treat other cancers like lymphomas. So you might have a patient who had a previous cancer been treated with an alkylating. Agent. Um, and that's increased their risk of a ML and they develop a ml. Um, so yeah, so we put all these things together. Um, and we have our patient. Okay, so when it comes to AML diagnosis, um, let me see the patient. We're gonna do a full blood count. Um, and we're going to see PANCYTOPENIA. So pancytopenia just means low. Uh, hemoglobin, uh, low platelets, low white cell count, and it's specifically low neutrophils. And that's what's going to expose you to lots of infections. In cancer, you get increased cell turnover, so you have I ldh ldh isn't specific to a m L, but it can be a sign that there is cancer going on. Okay, we're gonna do that blood test pretty quickly within 48 hours, I think, Um, but very quickly, because you want to know what's going on and then peripheral blood film. So we're going to see some blasts, so basically abnormal, um, cells, they're going to look quite immature. Um, and blast. Typically, you don't need to notice for your progress test, but they're going to be quite big. They're going to have a lot of cytoplasm, and they're going to have loads of Granules, So those are kind of blastic seen a ml milo blast, so they have loads of cytoplasm and loads of Granules in their cytoplasm and then auras. So we'll look at that a bit later. But that's very specific for AML. And when you see that you can kind of know that your patient has a ML and then the kind of the most important investigations to do a bone marrow aspirate and to look and see how many blasts are there. So more than 20% blasts, um is going to tell you that the person has a ML and then other tests are very important for hematologists. Not as important for medical student to know include cited genetics, which basically just means you're looking for anything like trans locations or dream deletions. Um, you're gonna do something called amino phenotyping. So you're gonna work out what kind of cell is affected in the cancer by looking at the market on the cell? Emelec, your tests look for specific really small mutations. Um, but those tests aren't as important for you guys to know. It's important to know that there is going to be more than 20% blasts when you look at the bone marrow aspirate and we're going to do a blood film and do bloods and then, in terms of general management, again for hematology and full cancers. In hematology, it's usually the same. We're going to give them chemotherapy. There's another different chemotherapy regimens, Um, so it's quite specific for each cancer, Um, you might use amino therapy to She didn't put on the slide, but that's another way to manage. Patient's bone marrow transplant can be really helpful. But if you remember, patient with AML are older and can be more frail, so we're not going to jump to doing the bone marrow transplant. Really, it depends on the patient, but we have to keep that in mind that they're older and could be more frail. And the support of management is really important. So you want to treat them with analgesia. You want to give them blood transfusions, depending on things like hemoglobin levels. Um, and we want to give them. We might want to give them allopurinal. And could anyone tell me why it's linked with, like, treatment? Yeah, tumor lysis syndrome? Exactly. So it's not just, um, leukemia. Also, when you cheat patient with lymphoma with chemotherapy, you can get a rapid destruction of these cancer cells and you get leaking of all the bad stuff in those cancer cells so you can get lots of uric acid in the bloods. Abnormal. Use the knees. You see hyperchloremia and high phosphate levels and low calcium levels. Patient's might have arrhythmias Um, and they might be quite unwell following the chemotherapy. So it's usually you're going to see a patient who, um, in an SBA who's had lymphoma, leukemia, had chemotherapy and now has abnormal user needs. Um, and other pyrinyl can be given prophylactically and another medication called respiratory. It can also be given prophylactically and treat humanizing syndrome. Um, OK, so time to your license in Jefferson. Response to the question in the chat because when you get, um, rapid breakdown of cancer cells due to chemotherapy, Um, and this leads to an increase in uric acid. So you get really rapid breakdown of, um, your cancer cells and why you give allopurinol specifically, I'll look that up. I remember being told it, um, there's two medication allopurinol and respiratory aids, but I'll double check why you develop, you know, uh, specifically and I'll respond to that later. Very good question. Um, okay, so that's acute myeloid leukemia. And, um, I mentioned it in the other slide. But can anyone find the important feature in this blood film that will tell you that this person has? Yeah. Mhm are all roads. Exactly. And these all rods, I'll just show you what they look like. So it's like these. They look like rods. They're going to be in the cytoplasm of these Milo Blasts. Um, so this is a blood film, and we can see that they have all rods, and we can kind of know that they have a ml Good. Yeah. So they are pathogen genomics. So they tell you that person has a amount. Good. Okay, so that was a ml, um, and then we're gonna be going to chronic lymphocytic leukemia. So kind of based on how I started this talk, can anyone tell me what cell is affected and see? Allow, um, specifically or what group of cells? The big, big clues in the title of the actual cancer. Um, see, uh, yeah, B cells, T cells. Yeah, so B cells. So we'll emphasize our B cells and t cells. But the main cell that's affected in cll B cells are B cells and T cells. CLL is very, very rare. So you're mostly thinking about B lymphocytes. But yes, you're correct. And it's going to be these more, more mature cells in the lymph oy lineage, the B cells. It did, uh, so with chronic lymphocytic leukemia, it's a slightly different presentations. The patient's are a bit younger than they are in AML, Um, so they'll probably be over 55. So still on the, you know, hippie older, but a little bit longer younger than a ML. So we have lymphoid cells involved or B cells, and these can live in your lymph nodes. So that's why we have lymphadenopathy. Uh, we can also have some better megaly. And this is because we have all these, um, increased lymphocytes that are going to infiltrate your spleen and call it to be bigger. And then we have other symptoms. So fatigue linked to the anemia infections linked to her, um, low neutrophils and bruising due to low platelets and then again, constitutional symptoms similar to your B symptoms. Fever weight last night sweats, Um, and it's important to remember that patient's could be a symptomatic. So clinically they do sometimes find these patient's without having many symptoms or no symptoms at all, and they find it on a routine blood test. And remember, when I said chronic cancers are more indolent, slow growth, slow growing progressive. So that's how you can kind of remember that they can be a symptomatic because it's more of a slow growing cancer and slowly presenting cancer. Okay, so with any questions, I'll try. And, um, if I don't answer them now, try answer them at the end. So you keep you keep asking. Okay, so with the diagnosis, we're gonna do the same thing. So are four ways. So we're gonna do some blood and we're gonna see an anemia and thrombocytopenia because we have all these abnormal cells in our bone marrow suppressing the other cells were going to have a high white cell count. And this is because we have lymphocytosis with loads of lymphocytes, but we're going to have very few neutrophils, and that's why we get infections and another kind of key s be a binding. Could be, um, warm autoimmune hemolytic anemia. So you might have a positive DAT test or a positive direct Coombs test, which is also linked to chronic lymphocytic leukemia. We'll do a blood film and we'll see increased lymphocyte. Um, and we'll see something called Smear cells are quite, um, good for knowing that the person has CLL, and then we'll do a bone marrow aspirate. Or you could do Burma aspirate or Linford Ass. Biopsy is not as important in see allowed to get those investigations, Um, and you can think about it in the fact that it's not the actual cells don't really live in the bone marrow, so it's not as important to do a bone marrow aspirate. But if you think they have a ML or another kind of cancer, it could be really helpful. You might want to do a lymph node biopsy to all that Hodgkin's, um, but it's not as important. And then other tests are really important to Hematologists would be the site of genetics, immunophenotyping and molecular tests, which not are not as important for things like s pas because they're very specific test. Um, but just to let you know that these tests you go on behind the scenes, okay, so management for CLL, it's a slow growing cancers, indolent a lot of patient's at first go into, uh, watch and wait approach. So doctors will observe them and monitor their lymphocyte count. And then when they get to a place where they're really unwell, maybe have really high lymphocyte count, then they might give chemotherapy immunotherapy again. Blood transfusions, depending on their hemoglobin levels, and then study for progress Has that might come up? You can get right to transformation. So this is the progression of CLL into quite an aggressive lymphoma. So you might have a patient who has cll and is doing okay. But then they become acutely and well have lots of lymphadenopathy. Um, and they have fever. Wait, wait last night sweats, and then you're thinking is their writers transformation? Um, so that's kind of a a good SBA question. Okay, good. Okay. So, um, what do you guys see in this peripheral blood film? Um, this person has cll smear cells. Exactly. So the smear cells are these cells here. They looks much, and we get them because the the lymphocytes and the blood of someone with CLL will be quite fragile. And when you prepare this blood for peripheral blood films, um, you're gonna damage You're gonna break these lymphocytes because they're already quite fragile. And that's why we have smear cells are so much cells. And that could be a good way to know that this person has cll maybe an s B a question. Okay. And then the last May counts. I'll talk about chronic Milo duty Mia. Um Okay, so the chronic myeloid leukemia. So what is the famous chromosome found? Um, in CML? Yeah, Philadelphia chromosome. Exactly. Um, it's a chromosome learned about quite early on a medical school. And it's a really important chromosome, actually, In CML, it's really changed how we treat it. So chronic myeloid leukemia. So we're going to think of it as a kind of a slower progressing cancer affecting the more mature cells of a myeloid lineage. Putting the chronic Milo together, and we're going to have this Philadelphia chromosome, so it's formed on the translocation of chromosome nine in chromosome 22. Okay, so, uh, Chromosome 22 has the B, c r. G, and a chromosome man has the able gene, and we're gonna put them together, and basically the B c r-gene it's. And then there's a gene that codes for a tyrosine kinase which is something that helps cells to grow and survive. The bottom part of chromosome 22 is really important in regulating be CR. So if we remove that bottom part, the B C R goes out of control and they want to refuse it with able. Able encourages it to get out of control even more because it kind of allows this gene to always be on. So that's why it's quite bad, because it allows tyrosine kinase this gene to always be on and allows cells to grow and survive, um, and not be negatively regulated by the bottom part. The crumbs in 20 g protein of Jean I mean or chromosome. Okay, that's just kind of background for the Philadelphia chromosome. We go. Okay, So patient's present around the same age as Patient's Percy allows of 55 to 60. They're going to have splenomegaly quite characteristically, because we have infiltration of all these my load cells in the spleen. They're gonna have fatigue because of anemia. We'll have again these constitutional symptoms like weight loss and night sweats, where they could be asymptomatic as well. So in the chronic phase, which usually lasts about 5 to 6 years, they're going to be usually asymptomatic in the accelerator phrase you might see patient, then presenting with symptoms. So this splenomegaly fatigue and that lasts a few months and then the really kind of bad phase. Um, it's a blast phase or blast crisis where we see blast forming in your blood cells in your blood film or in your bone marrow, you see loads of blast. Um, so hopefully we get patient's before they get to that place and treat them well. Okay, so diagnosis again, These kind of full ways, they do bloods and they'll have anemia. Characteristically, for CML, they'll probably have thermal citosis. They could have a thrombocytopenia, but they could have thrown bursitis. That's quite different from the other cancers where you won't get from both cytosis. You're going to have an increase in south of the Milo. Linear is the more mature cells of the Milo linear, which includes your neutrophils eurozone, a fields and your base ovales and your preferred blood smear. Um, you're going to see again. Increase in nuclear cells and nuclear cell just means white blood cells because the only cells that have a nucleus on a peripheral blood film should be a white blood cells. So increasing neutrophils designer clothes and both fields. And it's quite characteristic when you see a basic pill on a blood film is not is not normal, not usual to see it. So when you see many of them, we can give you a big clue that patient might have CML and again increased platelets, bone marrow aspirate again. It's not super important in this because we have really good genetic testing, which is quick, easy noninvasive. Um, and someone asked, How do you get John Russell introduces in CML? Uh, so I'd like to think of it as you get an increase in the amount of cells in your Milo Dinny ege that are more mature. And if you remember that kind of image, I showed you platelets and red blood cells. Do you come from, um, the Milo lineage? So that's kind of the way I think of it when it comes to thumb, bro. Cytosis, you can get thrombocytopenia as well. It's just quite characteristic. See thumb, bro cytosis In CML, we don't get obviously high levels of red blood cells, which is kind of confusing. We get anemia because we suppress the red. Um, let's cells in this cancer. But we can get high levels of platelets because they're in that myeloid lineage and we're getting more cells than my lord lineage. So hope that answers your question and I'll try and find a different answer. But that's kind of why they think we have thrombocytosis iss. Um, let's see. Okay. And yeah, So, like I said, Spicer genetic is really important for diagnosing CML along with blood and peripheral blood film. It's really gonna tell you, and it can be done really quickly. So, uh, this is fish. Um so fish is fluorescent in situ hybridization. Sounds fancy, but it's a very easy and quick test. So we're gonna look for the Philadelphia chromosomes. The fusion between be CR, which is on the chromosome 22 able to swim chromosome, um, nine. So the red here, this is going to show you. So this is the bigger chromosome. So it's chromosome nine with the able, and this is chromosome 22 here with the little green dots. It's smaller. Um, that's got be CR and then we're gonna fuse. BC unable. I'm going to have this uh, fusion dream. So it's just looking at those markers together. The B C unable markets come together then Karyotyping. So here we have You can see chromosome nine here. Uh, one of these chromosome nines is slightly longer, and that's because it's got a little bit of the chromosome 22 on the end due to the trans location. And here, chromosome 20 to this arrow is pointing towards that. That's the Philadelphia chromosome. So that chromosome has a fusion between B. C. R. And able is a bit shorter than the other chromosome 22 because the bottom of it has kind of been taken can joint up here. And you've got the fusion here from the chromosome nine. So I hope that's kind of explained it for you. Um, there we go. Philadelphia chromosome here The short, the smaller chromosome 22. Okay, so what's the name of the game changing drug for CML? What's the kind of mechanism of Axion? Yeah, matinee. Um, exactly. So the matinees is a really important drug of CML because up into the early two thousands that were using bone marrow transplant to treat people with CML when they had poor prognosis because bone marrow transplants are not. They're really invasive and there's a lot of complications. But now we have this drug you can give patient's. You can monitor them. They can have their living a lot longer. Now it's really changed the game For CML, it's quite a memorable drug drug because of its history. So basically the Taiwanese terrorism kinase inhibitor. And if you remember, when we have the b c are able fusion well up regulating the receptor kinase gene to be getting loads of cell growth and proliferation because that's what that gene does. But we're gonna inhibit the action of terrorism kinase. And hopefully we're gonna prevent this cancer from growing. Um, so yeah, and matting up has really changed everything. Okay, so we'll do some, um, questions now get a little bit behind time. But we'll do some questions, though. So, um, a 74 year old male, uh, Tom Smith presents to the hematology clinic with fatigue, ongoing chest infection and noticeable weight loss. Over the past six weeks, he has type two diabetes and takes metformin. He has no allergies, and he has a family history of prostate cancer. He smokes 10 cigarettes a day and drink eight units of alcohol week and usable or a driver. So those cultivations are normal except for a high temperature. On examination, he is pale with petechia on his chest. Um, and we see some blood results here, so red means abnormal. Uh, and, um, Green is normal, and I'll just give you a clue. That of the red meat is that it's all lower than it should be. And I'm just going to do a poll for people to answer. Okay? Yeah, that's fine. That's fine. Okay, so, um, which what did he have? Was the underlying diagnosis, Um, given his presentation, his symptoms as good results? Um, okay. The poll should be live. Okay, so wait a little bit. I'll wait like a minute. You think about everything, take it all into consideration. Um, his age, his his presentation, his blood results and what was the most, like, a diagnosis? Okay, so, 60 I guess 6% of you are saying, uh, going for be so I'm going to say take that as usual. Group answer. Just end the pole. Okay? Yeah. So 60 point view said be so. Yeah. So it's be um, so I try to explain it. So he's kind of he's an older male. He's presenting with fatigue due to anemia. Um, ongoing chest infections. We're not sure how many chest infections he's had. Book, You know, we're thinking it's an ongoing chest infection. Is not clearing has weight loss, which is a symptom of, like, basically any cancer. Um, so it's not that specific. And then on examination, we have features of his anemia and his thrombocytopenia and look at the results. He has low hemoglobin, low platelets, low white cell counselor pancytopenia. And he has low neutral fields, but kind of normal lymphocytes. Um, so we're thinking aml and this is because he has this kind of pancytopenia an older person who's quiet and well, so I hope it's clear why this person has a ml. Um, so I kind of get some answers. Why? It's not a l l um, So, um, no lymphocytosis or lymphocytosis will be a big give away in a l l you're gonna get lymphocytosis. I don't talk about it, But is it cancer that affects Children usually have two peaks, but it's quite characteristic. Think of it as a cancer or leukemia that affects Children because not many other leukemias you affect Children? Yeah. You'll get high levels of lymphocytes because it's a lymphoblastic leukemia? Uh, with chronic lymphocytic leukemia. Again, you'll have a high level of the emphasis i'ts. Chronic myeloid leukemia. Um, you're gonna usually have, uh, high neutrophils, not really low neutrophils. And you might get something Explainer megaly as well. Patient's might be a little bit younger and then small cell lung cancer. I mean, we don't really know anything about his chest and chest X rays, so we can't really say that. So I hope it's clear. But ask any questions if it's not clear, and I'll try to answer them at the end or as we go along. Okay. So, question, too. So, uh, some ricora 60 year old female presents to hematology hematology clinic with, uh, fatigue. Um, on examination, the hematologist find splenomegaly lab results. Uh, lab investigations are done, and we see a blood film below, So this question is a little bit harder, but have a think based on this presentation and the blood film, what's the most likely diagnosis? So we don't have too much information, but try and put together what we have. So we have splenomegaly fatigue. We have this blood film. Um, because see loads of nucleated cells. I'm not sure. Is there going to be a pole for this one? Mhm. Yeah. Hannah, I'm just doing it now. That's okay. That's okay. See, I'm seeing a lot of sees right now, Basically, all sees, okay. And the pole to didn't show results last time. Should I share results? Is that better? Yeah. If you press show results, they will share it to everyone. Okay, so everyone said basically, everyone's at sea. Um, and yeah. So you're right. You're all right at C. Um, So why are we saying it's see, we didn't give much information, So it's the most likely diagnosis. So at the age kind of fit CML um although, you know, it still could be a ML. We can't rule it out from this age. Uh, splenomegaly is quite a giveaway in, especially for CML. It can also be in cll. But remember, it's usually going to happen in cancers where we got loads of, um, cancer cells within the blood, and there's infiltrating the spleen. That's how we like to think of experimentally loads of cancer cells within the blood from them within the bone marrow. That's when we get splenomegaly and CML. And then the main global way is meant to be the blood film, which is hard to kind of know what's going on. I think, um, but the loads of nucleated cells to have loads of neutrophils, these kind of cells here hope you can see my arrow. These are all neutrophils. And then you've got a basic pill here, which you don't really usually see exception things like CML. And then we've got one blast sell here. So maybe they are like going into blast or the accelerated stage where it's like a few blasts. Um, yeah, well done, guy, because that was the main thing. Here was the blood film that kind of gave it away. And you guys did a good job too, about realizing your CML. Okay. And, um, the last cancer I'm going to talk about quickly is multiple myeloma, cause it's quite an important cancer. Especially when you think about progress tests and just in general as well. Um, so in multiple myeloma, that cancer cell, you're gonna have mutations in the plasma cells, but the plasma cells go back to the bone marrow, so it's kind of confusing. So the plasma cells, um, they're kind of these well differentiated cells that go back to the bone marrow and live there. So we get the cancer within plasma cells in the bone marrow and get loads of many, uh, many goblins. Or among antibodies or paraprotein. There's loads of phrases for loads of immunoglobulin. Usually I G um, that's the main one. You got loads of I, G and loads of abnormal plasma cells, and then we're gonna have crabs. So this is like something that everyone usually knows for their progress tests. So we have a high calcium levels, and that's because, um, these plasma cells in the bone marrow, they lead it, increasing the absorption of the bone. So we get loads of calcium, you know, dysfunction. Because always been a hi guys. I think we must have somehow lost Hanna. I'll see where she's going to. Hi, Hannah. We must have lost you. Yeah, I think sometimes I don't know what happened. It says I'm not able to start video, but I've connected to another my phone WiFi. So this should be more liable. I think my fire is not good. Sorry, guys. Um, let me share a screen. Yeah, he said, What's it on? I should I don't think my video is walking up. Okay, Just waiting for my video to turn on. Um, but OK. Sorry, guys. We'll continue with multiple myeloma, So we have lots of immunoglobulin. Like I said, don't worry about the video, Hannah. It's OK. That's fine. So we have lots of immunoglobulin I g causing high calcium, renal dysfunction, anemia and bone disease. And if I wasn't clear as to why you can drop me a method, but yeah, basically, um, increased bone resumption causes hypercalcemia the, uh, immunoglobulin the kidneys blocks up the blood vessels there. Suppression of red blood cells. And we have bonuses because of increased reabsorption of the bone. So increase osteoblasts increased osteoclast activity and decrease osteoblasts activity. Okay. And then, for your process is really important to know, you know, the diagnosis and what we see. So we see anemia. We see high, uh, esr. Because s are kind of measures them out of protein in your blood. It's inflammatory marker. So you could have loaded these immediate goblins will have high esr because kind of a I'm so sorry. I don't know what's happened. Usually mention it was really good. Okay, We'll keep going. Okay, Let's keep going. Just try again. Don't worry about it, Hannah. So, um, what do we see in this blood film? So, um, there's a few things. The arrow is kind of giving us a hint, but what do you see in this blood film? Exactly. The rule. It's formation. Bench Jones protein. We see those in the urine. Um, so you won't see this in the blood film, but yeah, we'll see the bench Jones protein in the urine, but yes, the rule X formation with the stack red blood cells and this myeloma cells going to look like an egg. So it's gonna have a nucleus. That's towards one side. Um, that's quite helpful in seeing a plasma cell and, you know, things. A plasma cell, because it'll be to one side. Yeah. Good. Okay. And our last question in malignancy. Uh, so Jaden Anderson, a 62 year old male presents with shortness of breath weakness, abdominal pain, thirst and bone pain Observations are with their normal range whereas hemoglobin is 97. So it's low and his calcium levels are high with 3.5, um, there are raised inflammatory markers. Um, later, serum protein electrophoresis and bone marrow biopsy confirms the underlying diagnosis. So what's the most important initial step in managing this patient? So taking two acceleration? Um, the blood results, how they're presenting. What do you think we should do for this patient? Um, as a fast as a first step as an initial step, you think there'll be another poll, and if not, drop your answers in the in the chart as well. Um, I'll have a look at both whenever you want me to share the results. Um, how's you? So, um, yeah, uh, share the results. We'll see them because you have too much time. Hopefully, we have a few answers, and if not, just drop in the chat. I'm seeing a lot of sees so you guys can see Yeah, So, see, And this is because, um, this patient obviously has multiple myeloma. Oh, not obviously, but the results have confirmed it. The protein electrophoresis confirmed that the bone marrow, but actually confirmed it haven't said, but they've confirmed underlying diagnosis. They have anemia, but they have this quite bad calcium level. So when you look at the nice guidelines, um, uh, calcium level of 2.6 to 3, it's quite mild. And then from 3 to 3.4, it's kind of moderate, and then over 3.4, it can be quite severe. And that's the kind of calcium, high level calcium where you want to treat with fluids and then gives Ellen John F a second. So I'm just trying to show that it can be overlap with other things, like hematology and other treatments. Um, so you're you're trying to treat how the Pacific patient is presenting? Uh, any questions? All the costumes. Hi. Sorry. The costumes high. So, um, the normal range is up to 2.6 between two. And 2.6. Um, so over 2.6 is high. So this patient has high calcium, not low calcium. Okay, good. Yes. So I didn't put the ranges, but over 2.6 is high, and over 3.4 is very high, so this patient has very high calcium levels. Okay, so we're not going to give you, um, a transplant first because that's not you. Never do that with any patient. A chemotherapy. You might need chemotherapy to treat this cancer, but it's not going to be the first thing we'll do. Um, and then the Spiro cases given to treat tumor lysis syndrome So as well as the allopurinol, which we mentioned earlier, and then zoledronic acid is the second step. Any tips on how to read nice guidelines for conditions There was so much going on. Um, I would say if you want to look at nice guidelines, look at it for the most important, uh, conditions Don't look at it for every condition, because some conditions you don't really need to look at the guidelines specifically, uh, things like a F or stuff. Maybe you look at the guidelines, but don't get too bogged down when you do questions, more and more will kind of stick with you the most important stuff, and usually you will get some kind of like reference range. Um, that could help you as well. Ok, so just quickly took to look at the SBA tips. So I think mostly in your free time. Have a look at this may be just so that you know what to look for. S B A s. Um so with leukemias with cancer of the blood. A very nonspecific presentation sometimes. But there are some features will give which will give the cancer away. I think so. If there's a cancer in a child is probably gonna be a l l if they're older and especially to have your rod aml with cll might look for things like Samir cells. Question Might have writers transformation with CML. Definitely Philadelphia chromosome. As soon as you see translocation 9 22 you're gonna think, Oh, CML and a matter neighbors a key treatment and with multiple myeloma crap. Um, so, yeah, just a few things to help you know which cancer they're talking about or what kind of cancer and what kind of treatment might be the best option. Um, but apart from CML, all the other ones have very generic treatments of chemotherapy immunotherapy, um, and things like that. So yeah, Thank you for sticking with me through that. And for I'm sorry for all the connection issues. So we'll talk about anemia. Next. We'll try to go with do it. Um, get a good pace so anemia. So what is it? What does it mean? It just means having deficient red blood cells were deficient. Hemoglobin and clinically, it's less than 100 and 15, uh, grants police and women and less than 130 in men. So signs and symptoms of anemia. So I've kind of gone through them a little bit for the cancers. Um, So what? What do you guys think people will present with if they have anemia? Um, loads of things. Yeah. Fatigue short of breath. Fatigue, weakness exactly. Tiredness, shortness of breath, fatigue. Exactly. So it's quite a vague presentation of someone who's being tired. Short of breath. Um, very angina. Yes. So, uh, so it could be fatigued. Might have palpitations or tachycardia. Or maybe some chest pain, like someone pointed out, might feel a bit dizzy. Or they might have episodes. Whether fainting a lot might have cold hands and cold feet might have shortness of breath, they might have women. When you do an examination, then you might see some, like conjunctival pill ore, which you know, always pulling down eyes. And we're looking for some conjunctival pill or so. Yeah, So loads of symptoms might be like you said week. Um, my has quite specific symptoms as well, depending on the type of anemia. So, um, when we're looking for anemia and we're trying to work out what type of anemia or how to classify it, what other results other than chemo globe in, um could be important in, like, helping us see what type of, um, an email. Your MCV MCV is really important because it helps us to work out. Over Is microcytic microcytic normocytic? Anything else? That's the main one yet Iron City is good. Oh, the acid. I can't pronounce that, but yes, very good. Iron City is good. Fantastic. Um, so your MCV is the most the most important thing when you're first looking at anemia. But, yeah, iron studies can be really useful, especially for iron deficiency anemia, which is the most common type of microcytic anemia. Anyway, particular sites can be quite good, because if you have an anemia and you have loads of particular sites, you can show that the bone marrow is working hard to produce red blood cells and particularly if they're just kind of like these early precursor red blood cells. They do circulate in the blood, but they'll circulate more if you have an anemia and your blood marrow. Your bone marrow is trying to push out more bed cells. And then if you have a hemolytic anemia, you might find high levels of bilirubin, especially if they're drawn. Dissed? Um, you might see that. And it's gonna be unconscious gated because it's before the bilirubin hasn't gone through the liver or the bald ups or anything like that. Questions? Yeah, full. It beat up. Exactly. Exactly. All these all these, um, investigations are very useful. Okay, so types of an email, so I'll go through them. Um, so microcytic. So we usually the MTV of less than 80. The most common type is iron deficiency anaemia. You can sometimes have anemia of chronic disease in the microcytic range. Although usually in the normocytic range and alpha thalassemia, in a progress has questioned it might have, characteristically, quite a very severe uh, microcytic picture. So with someone with alpha thalassemia, you could have kind of a medium ish or slightly low hemoglobin. But then a really low MCB. So that's kind of like a a characteristic thing for alpha thalassemia. Really low MTV normocytic so usually going to be with an 80 and 100 MTV and humanistic anemia is going to fall into that hemorrhage. When you have an acute hemorrhage, you probably will see normocytic anemia and anemia. Chronic disease is more likely to be a normocytic anemia because of, um, a balance kind of between iron deficiency anemia and other types of anemia, and then macrocytic so with an MCV usually of more than 100 and have megaloblast ick and non megaloblast ick and essentially megaloblast ick means that there's an impairment and DNA synthesis within the red blood cells. Um, and that's going to be infected by having a B 12 deficiency or folate deficiency and with detailed deficiency can be caused by a few things like pernicious anemia, which is an autoimmune disease. Um, and you might have some neurological symptoms as well in your presentation with B 12, and then we have non regular plastic. So alcoholism, hypothyroidism, hepatic disease, there's quite a few causes. So yeah, this is how we think of anemia. Microcytic, normocytic and Macrocytic. Okay, so let's start with as soon SBA now. So join Meridia, thought a 32 year old female presents to her G P. So what is Mega bus? Okay, so before we do this question to answer that question so megaloblast it just means there isn't a problem with d n a synthesis within the red blood cells. So Foley in B 12 or to do with DNA synthesis within the red blood cells? Okay, I hope that answers that question. So no. Yeah. So question four. So during Marie, the, uh, 30 year old female presents her GP with tiredness over the last two months. She does not experience any, uh, other symptoms. She has normal periods every four weeks, no relevant past medical history and does not take any medications and has no allergies. She has a family history of I B. S. She works at the school teacher and has been a vegan for years. And there's no significant examination findings, So hemoglobin is 100 so slightly low, and she has an MCV of, uh, 78 so slightly know and other laboratory results are not significant. So, given her presentation, what's the most likely underlying cause of her anemia? So is it gonna be, um, my absorption of iron malignancy menorrhagia reduce absorption of B 12 or reduce absorption of iron. Okay. Uh, okay. So I can't see the pole. The pole yet, But whenever it's available, can see what's going on with the pole and what people say. Okay. Uh, so, yeah. So most of you saying you reduce the absorption of iron. And yes, that's what I'm trying to get you to think about. Uh, there's not many other reasons this patient could have an iron deficiency anemia. So my absorption of iron is a cause of iron deficiency anemia. But usually I'll get features of other conditions that cause my lab absorption of iron like inflammatory bowel disease and celiac disease. So you might get a weight loss, abdominal pain, and, uh, something on the bloods that could suggest celiac disease or i b d again malignancy. There's no weight loss or rectal bleeding or anything that could address malignancy. Man, Arranger. That's a very good one to consider in any you know, woman. But she doesn't have any heavy period, and she's not complaining of it. Reduce the portion of details would call the macrocytic anemia. And, yeah, so she's a vegan. So maybe, you know, she's been a vegan for years. Maybe she's not taking iron supplements anymore. Maybe she never did at the beginning. So that's what we're thinking of is the most likely underlying course, because we don't really have any reason to think of the other reasons as being an underlying course. Okay, so well done. So iron deficiency anemia. So let me think about it. Deficiency anemia. There can be a few presentations that are quite a guess. Unique for SBA questions. I guess so. They might have mouth ulcers. Um, they might complain. Amount ulcers. They might complain of symptoms of anemia like fatigue. Um, there might be a symptomatic. So they might not have anything going on with them. And they're coming in for a routine check or something else. Um, And then when we think about other unique findings that are not as common kind of angular cheilitis so you can see around the mouth is quite sore or atrophic glossitis. So if this image here, it looks quite glossy. This is a normal tongue, and this is the kind of a trophic tongue Looks quite glossy, a bit bigger colonic ear, which is just, uh, spooning of your nail. Uh, so those are kind of could be like indications for in deficiency anemia that are less common. And then we're gonna do blood. Um, we're gonna see a low hemoglobin. And low MCV is the main things we're gonna think, um, as well. And then we're gonna do iron studies, which can be quite useful. Um, so we can see that usually they have low iron, low transferring saturation. Increase a total iron binding capacity because your blood cells want iron, so they want to bind to it. And then ferritin is another part of the STDs. But ferritin is also an inflammatory marker, so it could be low, but it also could be normal. Or it could be raised due to inflammation. So it's less specific and less good at working out. If we have iron deficiency, anemia and then blood film, you can actually hypothermic microcytic cells. But really, all we need is a full blood count. Uh, maybe an iron studies to help, but it's the most common cause of anemia, so we don't really need to do a blood film and stuff. And the management we're going to increase dietary iron through eating food that has iron. Um, we're gonna treat the cause. So if we're not satisfied that it's due to, you know, dietary causes, it could be underlying inflammatory bowel disease. It could be cancer. So then you want to refer to specialists and treat those causes. Iron supplementation is really important. Usually you give, you don't need to remember the actual like, um, amount, but usually give oil ferrous sulfate 200 mg twice a day or three times a day for three months. Then you check on the patient. Um, you know, tell them you're drinking with orange juice, Um, and watch out for GI disturbance like constipation, diarrhea. Eat it with food as well. Um, and then blood transfusions if severe anemia. So not most patient's. But if you have severe anemia, then we do blood transfusions and then referrals over sixties with for, um, colorectal cancer. They have a low, uh, hemoglobin or iron deficiency anemia because they're worried about underlying malignancy as the cause rather than dietary causes. Yeah, that's the main thing. And just to show you this is a normal blood film. So we see loads and loads of Senna normal Red film will see loads of red blood cells, which are not nuclear cells. We see some platelets here, these little things here. And we see some nucleated cells, which are your neutrophils right here. And then this is meant to be Show you, uh, iron deficiency anemia. Uh, it's a bit blurry, but we can see this cell here has got an area of Central Pelosso. It's hyper chromic. And, um, you can't really compare between these two, but it's meant to be a smaller cell as well. See, I just to show you the normal blood film. And this is slightly abnormal with hyperchromia and macrocytic. Okay, Deficiency anemia. Okay, so question five. So Jose Rodriguez is a 69 year old male presenting to a and E with upper abdominal pain and hematemesis. Oh, he sorry has a past medical history of CKD and osteoarthritis, for which he takes ibuprofen daily. And he has no allergies. Um, his hemoglobin A 60 g per liter. How she reminded, um, the anemia here. So should we give blood transfusion? Should we give Aretha poet Ian? Should we give am hydroxy carbo? Um bellamy? And should we give IV iron, oral iron? How do we treat this anemia, considering the hemoglobin, their presentation. Okay. Should we have a look at the results? How much of there was a poll? Actually Oh, there we go. Yes. So every, uh, 57% said a good if you said be if you said d she said E, But the answer is a, um So this patient. So I'm trying to get you to think that this patient has, um, is having a bleed because of the history of NSAIDs. I'm thinking they probably have a ruptured, um, ulcer. Um, but they're presenting quite unwell with pain and hammer to missus so and a low hemoglobin. Um, so the hemoglobin slightly change from the last page, but it's meant to be the same. Um, So you wanna wanna transfuse them with blood with red blood cells? Um, and according to nice in patient's who are stable. Um, if the hemoglobin is less than 70 we'll give them blood red blood cells. And if the hemoglobin is less than 80 in patients with acute coronary syndrome and give them red blood cells for those markers are for people who are stable. That's when we use restrictive standard. But if someone's really unwell, has a low hemoglobin were less likely to use these kind of standards. But just so that you know, And then it was the protein. Uh, I threw well for the CKD. Think, um, they might have an anemia due to CKD, but this is not going to help their current situation. And then the i m b 12, which is C. That's for people with pernicious anemia. We can't absorb anemia properly, not anemia. Absorb B 12 properly. Um, so that's what we give for them. It's not for acute bleeding. I v i n That's what people who, uh, don't tolerate, uh, oral iron supplements. Very well. Um, and have, uh, intolerance to it may be due to side effects like the G eye irritation and then all iron again. This patient's hemoglobin drops significant. It's probably due to a bleed, so we're not going to give them all iron. Okay, Just checking any questions. Good. Okay, that's clear. Okay, So, um, and our in okay, bleeding disorders hope everything has gone well, there's any questions. Please drop them in. I know. I I left. So then some questions we're missing, I think, um But if you want to send them again, please feel free to, and I'll try and answer them. Okay, so we have bleeding disorders now. Okay. So just go to go through normal costing. Very simply, Uh, So when we think about crossing, we need platelets, and we need a coagulation coagulation factors. We need these working together and working well, So when we bleed, we have an or blood vessel, which then, uh, injured. And then we have exposure of collagen and the plates. That's kind of stick to explode site. And we get, uh, fibrin mesh, and we get this clot. And that's how we get good clotting. Be good. So you're helping each other out, and the child is good. Okay. Um, so does anyone know the normal range? Your platelet counts. It's quite a big range. You don't really need to know it, but, um, I didn't want to do it. 302 150 close. It's from 100 and 50. So Yeah, so it goes. It might even be 100 50 to 500. I'm not sure, but basically the cord is like there's a big range 150 is on the lower end. Um, and what are some examples of bleeding disorders that you guys know of? There's quite a few. So think about when there's low platelets or problems with coagulation factors. Yeah, exactly. So hemophilia one. Gillibrand's I t p TTP. Exactly. So today I'll focus on the platelet ones more so than and the acquired one rather than the inherited ones. Um, so let's start with I t. P. So I t. P is, um, there is linked with, um, an immune response against your platelets. Um, there's several mechanisms for why people think it happens. It can be autoimmune, but basically your immune system attacking your platelets. Um, it's usually self limiting, and it's usually following a viral infection. Sometimes vaccinations. But I think typically in a in an SBA will be a viral infection. And you'll see this low, uh, platelet count. So less than 100 and 50 or threat to actually be to cause bleeding usually less than 50. The platelet count. So the patient will present with bruising ti chi bleeding from their gums, uh, epis axis know be menor Asia, and there's different time frames for I t. P. So an acute I t p would be less than three months and then persistent, um, 3 to 6 months and then chronic more than six months. Um so like I said, it's mostly self limiting. So management for every patient would be We're going to monitor your platelets, maybe weekly, maybe every other week, and we're going to give them good education. Like, don't you know, if you think you've had a head injury and you feel confused and dizzy come into A and E, there could be a bleed. Be careful. Contact sports. Just be careful in general because there is a risk of bleeding and then further management. So this is gonna be usually indicated by like, um, having maybe a more chronic or persistent I t. P. And it's probably gonna be started by a hematologist, but you can get them steroids. So when you have an S B A, and there is a treatment option is probably going to be steroids. First line. Things like China stomach acid might be helpful for, um to the patient, and then other further therapies are going to be I v i g, which are going to attack the antibodies that attack the platelets, which took the map which attacks the B cells, um, prevented them from releasing, uh, immunoglobulins attack the platelets. And the split next to me is, like, really like the last resort you don't want to do, you know, split next to me, even though it's quite effective. You don't really want to do it. Um, and it's effective because the spleen is where or your damage platelets go. So if you take other, please spleen, you can increase your platelet count in your blood. Um, yeah, not ideal. So it's kind of steroids are your first line thing after you kind of see if it goes away on its own, and then TTP, which is kind of harder to, uh, grasp, I guess. Um does anyone know, like like the pen tad or the five things or some of the five things that patient's present with when they have TTP or the five things they include? An S B a s more. So. One of them is number cytopenia. Yes, A breezing. So it's like a pen tad impeding some cytopenia A fever. Exactly. Neuroscience. Exactly. Like seizures. Yeah. Coma. AKI. Yes, Serena impairment. It's one of them and email. I think we've got all of them now together. So N T T p Basically, we have a condition where, um at first we have, um, lots of thrombosis and your small vessels, and then all your platelets get used up. So thrombosis. First, all your platelets get used up. Then we have thrombocytopenia leading to bleeding, and it's usually an ultra immune condition, but it can be also a genetic condition, and it can be kind of have an inheritance pattern, but that's not as important to know. Um, and it leads to that that pent add. So you're thrombocytopenia because you used up all your platelets. Now we have low level of platelets, platelets. We have red cell fragmentation or, um, your red cells kind of been broken down. Um, we have fever as well. So, um, and we have transient neurological deficits or things like headaches, seizures, comas and kidney failure. Uh, and how we manage it is with this diagram you can see here it says usually pleasant exchange so you can get hematologist involved. Do plasma exchange. Also give them things like steroids and rituximab as well can be quite useful, but your plasma exchange is kind of known to be quite useful. Okay, Um but yeah, that's TTP. So the most important thing to realize that pent had, I think when it comes to SBA questions. Okay, so, um, this person has TTP. What is the finding that we can see in this blood film? It's related to what I said about red cell fragments, but it's like a name for it. If anyone knows the name. Yes, Shift decides. Exactly. So it just reds are fragments is not exclusive to TTP. Other conditions can have, um, sister sides too. Um, but yeah, that's a good finding that they might be able to show in an S B a question for TTP. Okay, so another question. So so on the topic of bleeding disorders. So a seven year old male presents to the pediatric A and E and wild tummy pains and bloody diarrhea over the past a few days following a trip to the farm has no significant birth or past medical history. Um, and has had all the vaccinations, don't have any allergies. His observations are normal and he's stable. Um, on examination f to notice a particular rash on his abdomen. His blood results show anemia, thrombocytopenia raised white cell count and CRP. Um, raise urea and creatinine, and the store culture results are on your right. Right here. So given this presentation, the blood results, the full culture results. What does this patient have? And, um, you can see the results as soon as Yeah, be so everyone's saying be sent to 1% would be so we'll go with that. And yeah, you guys are right. So I try to do a quite a classic presentation of humanity remix syndrome. So this patient has the symptoms, so they have a, you know, a bloody diarrhea and tummy pains giving you a picture of gastroenteritis following a trip to the farm. Um, and they have the triad of anemia or hemolytic anemia. To be more specific thrombocytopenia and renal impairment and the stool culture result. This really tells you because this E. Coli 0157 is quite a key. Um, it's what's going to cause, um, him elliptic remix syndrome because of what it produces that produce the sugar toxin, uh, and that causes hemolytic uremic syndrome. It causes this triad of result and yes, so it's quite a nice SBA question because it's quite noticeable. Um, and like we said, they'll present with features of gastroenteritis. Probably that will present first. And then they might have other symptoms, like funeral impairments. They might have blood in their urine. They might have reduced urine output and they might have, you know, bruising patiki eye from the low platelets. And it's due to this sugar sugar toxin, um, and typically affects Children. So the patient's are likely to be younger in their SBA, so we don't want to give them any antibiotics. Um, we want to give them supportive management as appropriate. So if they have really bad anemias, you might think of giving them blood transfusions. You're gonna give them supportive management, and we're gonna notify public health as well. Um, so good. That's the nice STV a question to have. And then d I c what happens, um, as a consequence of something else. And this is usually sepsis. Um, I'm still here. Good sepsis or malignancy? Particularly, uh, acute myeloid leukemia is linked with it. Upset your complications like help syndrome and then trauma. So basically, you're gonna have something really bad happening before, and then you'll get D I. C, which is also really bad. And then you do the blood and you'll see thrombocytopenia and then you do their coat screen and you'll see basically everything going wrong. Um, so you'll see high, uh, prothrombin Teen High A P T T and lo fibrinog in, um And just to go through why you get it So it's caused by you know, something going on in your body that's going really wrong except that you get systemic inflammation and you have lots of similar to TTP. You get loads of clotting first, which usually all your platelets, these are all your platelets, all your coagulation factors. And then you have low platelets, which leads to bleeding. So that's how you get d. I see. So it's like called, uh, consumptive coagulopathy use it for your platelets, and then you get nose of bleeding. Um, following all that kind of microvascular thrombosis, okay, so underlying, So you're gonna treat it by treating the underlying cause, So whether accept it or the malignancy, you want to work on that, you're gonna treat them with supportive care, so blood transfusions are very important especially for platelets. Fresh, frozen plasma crying precipitate. Because these have all your clotting factors. So it's mostly supportive and the unknown nice. Ghilas have also a measure for when you give platelets. Uh, I think platelets can go quite low. Um, so below even below 30. So when it goes below that, you might think of giving a transfusion for platelets. So it's slightly different to the hemoglobin. Yeah. So under 30 give a blood transfusion, but yeah. So those are the beans orders we talked about, So h u S d i c and then I t p and T t p. There are quite a few other ones that we have hemophilia A which excellent recessive. So mostly seen in males and usually get collection of blood in the joints or Highmark process. That could be a can sp a question. And then from willebrand disease autosomal dominant or recessive, depending on the type, um, again be eating disorder and heparin induced thrombocytopenia so following heparin. So I would say maybe have a quick look at a YouTube video all through on all three of these. Um, if you have time, um, that could also broaden your understanding of bleeding disorders. Okay, so we've done bleeding disorders. We did that quite quickly, so I'll have a look at any questions. Okay, So given the question, what makes it hate us or not? H S p. It's a good. That's a good question. Uh, so if you look at the question again, it's very quickly. Thank you, guys. Okay, so HSP again. These are all these are all really good differentials. All these answers a c d e. A good differentials for anyone for any child presenting with, like, a rash, a particular rash H s p um so you could get things like tummy pain as well. But usually this patient has a history of going to a farm, getting some kind of infection. And also, this positive stool culture is going to tell you that it's not hs psh us. So, H s p, you're gonna have tummy pains as well. You're gonna have a rash as well. Um, you might get knee pain or joint pain. Um, so yeah, so the main indication is this positive E. Coli 0517 0157. So, yeah, I hope I answered your question. Why not antibiotics and h us. It's called by bacteria. Good question. So when I looked it up, it just said, Antibiotic actually makes chus worse. So clinically, the outcome when you give antibiotics is worse. Um, so, yeah, that's why you don't give it. I can look up an email you back. Why? It makes it worth, but it's not good. Um, and that's why gastroenteritis they treated with antibiotics with caution because of, um, the fact that could make a US worse here to speak and follow on from an infection, though. Yes, that's a good point, but this specific infection, E. Coli 0157, is linked to h US. More if I'm correct. If I'm not correct, um, feel free to correct me, but I think it's mostly linked to H. U S. So the main thing in the question is this Positive E. Coli 0157. But they're all good differentials who are patient's with having, uh, a non blanching rash anyway, So I hope that answered the question. Okay, so and we're aware that we don't have much time left, so I'm gonna go through red cells, orders. Um, briefly. There's quite a few, but we'll try to go through the main high yield ones and hopefully answer some questions as well. So let me talk about red cells orders. We're gonna think about what's actually going on with the red cell. So there's a very, uh, not common disease disease that we learn about quite often that causes a problem with the red cell membrane itself. Anyone know what that is? So one of them cause the problem with the red cell membrane sickle cell? That's a really good answer. Single South is a problem with the hemoglobin. More than the red cell membrane. Um, but, yeah, we're gonna talk about sickle cell later. Um, so hold that answer G six pd a very good answer as well. We're going to talk about that later. But that's more of a problem with the function of the red cell. Prevent Terry Spirit cytosis. That's the answer. Yeah. So really good answers. We'll talk about all those later. So hereditary spherocytosis is caused by problems with the red cell membrane. So it's due to problems with proteins in the sight of skeleton called ANC urine and, uh, spectrum don't know goes particularly, but We just need to know that it causes a problem with the red cell membrane, which leads them being an abnormal, abnormal sphere shape. So that's what causes for a citosis abnormal sphere shape that makes it more likely to break down due to mollis is because it's not a very good red blood cell. Okay, so presentation patient's are gonna be fatigued because they have these abnormal red blood cells that aren't working properly and there are breaking down quite easily. They're gonna have jaundice because you get lots of hemolysis or red blood cells. Um, and patients can present with neo neo neonatal jaundice. You might see a baby with jaundice, and they could have hereditary swear citosis. That's splenomegaly because you're breaking down all these red blood cells, um, in your spleen. So it's gonna get bigger and then usually seen in people with northern European in the stent. And it's inherited in an autosomal dominant condition so they could have a parent that's affected. And it's important to know that if a patient has the symptoms and then, um, has a history, maybe of an infection with parvovirus or they have anaplasia, which basically means your bone marrow is not working. You'll get no hemoglobin know platelets, No white cells. This could be due to an infection with parvo. Virus is a very common virus that causes slapped cheek in Children. But it causes aplasia on a plastic crisis in her Virgin Mary Spherocytosis. That's the key. Kind of s be a question. Why isn't the bone marrow working? Why is a hemoglobin so low? Probably just a part of the virus. So for diagnosis, um, we're going to do some blood. We're gonna do normocytic. We're gonna see a normocytic anemia cause it's he, uh we're gonna see Humala, Sis, we're going to see an increase in MHC. And I like to think of it as the meaning that the cell is more like, um, it's it's more compact, so it's going to be more dense, and it's gonna be more dark. And that's why we have an increased MHC. So it kind of tells you how dense the cell is or how much hemoglobins in there within. It's kind of concentration. Um, that's why we have a high mh secrets more dense and then high bilirubin because we're having lots of him. Alice iss particular cytosis. So if remember, you get high particular sites when your bone marrow is trying to work hard to produce more red blood cells because it's not sure what's going on. Why is there so much hemolysis? They're going to try and work hard. We're gonna try and work hard the bone marrow and produce more red blood cells. Okay, so if the blood and then blood film, let's see spirit sites. Um and we're gonna for diagnosis that really help. We can do something called E. M. A binding. Okay. And the management, we're gonna think so. They have low hemoglobin. We might do blood transfusion, depending on what the hemoglobin is. So it was less than 70. Like we said, they might give them some blood transfusion with red blood cells, folic acid for supportive management. And then the next thing we can be quite effective because you just get a really big spleen because that's where all the cells are getting chemo realized, so it can be quite good. But what is the issue with the neck? Tammy's If anyone knows, I guess. Feedback link. If anyone needs to go, go free and give me some feedback. Yeah, I don't really have too long left. If you want to hang on, I'll try to make sure it will be most concise. Um, so there was an issue with connect Amis. And why? Why could there be an issue and someone, Especially if it's like a young person with a spin it to me? What do they have to think about? Yeah, and calculated bacterial infections. Exactly. Um, so, yeah. Risk of certain infections that meningococcal infections here. Metalist, um, streptococcal infections. Um, so they might need to have They need to have their vaccinations. Um, and they need to maybe have prophylactic antibiotics, depending on, um, each patient, but yeah, risk of infection because of the, uh, pen optic splenectomy. So you have to think about it before and counselor patient before doing it. Okay, So what's the important feature in this bit film? They do have hereditary spherocytosis iss. So what uh, feature did we talk about in other slides? Circular red, blood cell. Yeah. So we're going to see this, uh, spirit site, so it's kind of it's more dense. Red blood cell. Can you see? It's kind of a dark, like I says, more compact. Um, because you have red cell membrane disorder. It's not really, you know. It's a fair ical. It's a spherical red blood cell is a bit more compact. It's going to be a bit darker. Okay, good. And their problem. Red cell functions If someone said it earlier G six PD deficiency, that's going to cause a problem with red cell function. And that's because the rebels cells really depend on G six pd, um, to protect yourself from oxidative stress. So all your cells have G C H, P D. But red blood cells. But your other cells have other enzymes that can help with oxidative stress and protecting cells from oxidative stress or red blood cells. They only depend on G six PD to protect it from oxidative stress. And that's why red cells are affected by this deficiency because they really need the Six PD. Well, your other cells don't need to add much. Um, so they're gonna present similarly to hereditary spherocytosis. They're gonna have fatigue and drawn district to Hamal, icis and gallstones as well, due to Hamal Icis and build up a bilirubin. Been a megaly because that's where we get all this breakdown of your red blood cells and then they're going to be usually of a Mediterranean African descent or Middle Eastern. Um, it's associated with certain triggers, Um, which will go through after. But that's quite a good s be a question when they have triggers. And then they have this picture of fatigue and jaundice that's quite classic picture. And then it's more common in males because of the X linked, recessive pattern of inheritance. Question. Oh, yes. OK, thank you, guys. Feel free to leave. This slide will get sent to you. So if you need to go for free to go, OK, so diagnosis, um Bloods. So we have enormous citic anemia again because of the hemolysis and high bilirubin higher articular sites. Because your bone marrow is working hard to push out these red blood cells. Your blood flow is gonna be quite interesting. You're gonna see Hinds bodies and blister cells and by itself, which we'll see later on and then to diagnose it could be really important to do a G six PD enzyme essay, but we're gonna wait if they've just had been exposed to a trigger like father beans, which will go through after. We're gonna wait around three months because we don't want to have this trigger affect the results for your G p C a g six PD enzyme essay. So we want to really get a good result. Um, and the management avoid triggers, and blood transfusions is quite simple. So we'll have what the triggers are and just avoid them and treat their low hemoglobin. So, what are the triggers of G six PD? What could be an SBA that could trigger d six PD? I mentioned one of them earlier. Antimalarials good father being is good. So for fuck's in in? Yeah, exactly. You guys sulfa drugs? Exactly. So, uh, father beans, that's like a good question where they have father beans, They have, like, drawn dish and fatigue after, Um, I'm not sure father beans and broad beans are the same. I think they could be the same. Um, but yeah, they kind of use both interchangeably. Primaquine an example of anti malarial. They have antibiotics like ciprofloxacin, Natural fluent. Oh, and trimethoprim. Um um and the sulfasalazine, which is like an anti Um uh, Dmard is also used for IBD. So for your ears use for diabetes and then viral infections as well. So with a lot of these, um, red cell disorders, royal infections can be a trigger. Can trigger hemolysis can trigger aplasia. Um, but, yes. But typically we get these, like father beans or broad beans are linked with G six PD and these antibiotics and primaquine so good. So yeah. So to show you here, we have bite cells. Um, and we have hines bodies. So Heinz bodies are formed because of the hemoglobin being degraded due to oxidative stress and then by itself, a form because the macrophages kind of bite the degraded hemoglobin. So that's kind of why we get these. Uh, they look kind of similar to hold jolly bodies, but I like to think of them as being more on the edge, and much of that's actually correct. But I think of them as more on the edge. Um, and then put it together with the clinical picture will help you to figure out um, that is a highest body it presents with G six PD. Okay. Uh, so so this question. Samantha Evans, a nine year old guard sense to the hematologist, withdrawn this tiredness. and a large abdomen. She has no relevant past medical history and had all her vaccinations and doesn't take any medications and has no allergies. Her mother has a history of gallstones and had a spin it to me. Um, and as a t as a teenager, given the most likely diagnosis, what is the most appropriate investigation to perform on this patient? So it's e m. A binding is a genetic testing to six p. D enzyme s a hemoglobin electrophoresis osmotic fragility. Um, so, yeah, Whenever the poll is ready, you can see what you guys think. Yeah, e m a binding. Exactly. Well done. So e m a binding Because we're thinking this patient has hereditary spherocytosis iss. And why? Because she has, well, like a b g six pd from her drawn this tired, this large abdomen. You know, there isn't much from that, but we can think about the mother. Her mother has a history of gallstones and splenectomy, so her mother probably has a budgetary Spiro cytosis. And if you remember, it's an autism or dominant condition. So that's why I'm It's more. We're gonna think Herridge risk for a cytosis. And we're gonna do an e m A binding test and the genetic testing isn't essential to diagnose uh, surgery for cytosis d six pd NDM Actually a good test to do, actually. But we're thinking more e m a binding the better test because it's more pointing towards very thorough citosis due to the mother and her symptoms and then hemoglobin electrophoresis. That's more for sickle cell anemia, thalassemia and then asthmatic. Fragility is a test for H s, but it's not really used anymore. It just test how fragile the red blood cells are. And they're quite fragile in H s. Yeah, well done, guys. And then it's the last part. So we're gonna talk about sickle cell and thalassemia. So these are hemoglobinopathy hemoglobinopathy. Um so with sickle cell anemia, you get to, uh, you inherit two of these tickle cell genes. So it's also a recessive condition that usually affects West African people and Caribbean people in the UK um, and also affects African American people in America and obviously African people and, uh uh, West African people in Africa. So it's a worldwide condition. It's a very common also, um, natural trait. Sickle cell trait is a very common thing to have and then the anemia is quite severe. It's really it just really affect people's lives. So it's something that is worth knowing about. So, yeah, so six anemia is H B S s. There's loads of six old disorders, technically, but six Alinum is HBs s, and it's caused by a mutation. Um, that leads to an abnormal beta globin chain. So in the global part of hemoglobin, you have alpha chains and beta chains, and in sickle cell you have an abnormal beta globin chain. And then when you put that, uh, hemoglobin under stress the oxygenation, like when you exercise or when you're stressed or when you're, um, high altitudes you call sickling or the regular cells, and that leads to face of occlusion of your vessels and also chronic analysis. So that's kind of the pathogenesis, and you get loads of complications, lots of prices, lots of pain. Um, is diagnosing something equal that hemoglobin electrophoresis and high performance like chromatography. Not as important for SBA is but good to know that antenatal screening there's newborn screening with a heel prick test. Um and yeah, as managed, you need analgesia. These patient's on a lot of pain. Acute and chronic blood transfusions. Hydroxyurea is really important. Folic acid as well. And penicillin because, um, your spleen isn't working as well. Um, you're more prone to infections. So it's good to have penicillin. Yeah. Okay. Good. Um, so, yeah, I'll quickly go through this, So Yeah. So this is someone with sickle cell, but they have loads of features. So the first feature here is how jolly body. And that's a sign of hypersplenism. So when your spleen isn't functioning as well, or when you've had a splenectomy, you can get how jolly bodies. Um, so it's not just exclusive to sickle cell. Just one. Your spleen isn't working. Well, target cell. So again, that's not specific to sickle cell. Um, it's a sign of anemia. So we have this area that's not actually a target cell. Let me just make sure it is. There's definitely target cell in here targets. I just have a bullseye. So that's why I'm querying this target cell. Okay, so the target, I will have a bullseye. I'll probably end of the image just to be sure that it's target Cell will have a bullseye where it's red in the middle, and then an area of blow outside. And there's sickle cell. That's the main finding in here. So yeah, that's specific to sickle cell anemia. Really? Um, but yeah. And that happens when your your cells are under stress and it causes this sickling. Um, yeah. And then these are the diagnostic methods. Just so you have a bit of background, you don't need to know these Really? But in someone who's normal, you have three types of hemoglobin. So the main ones hemoglobin A and then you have haemoglobin f which is in your fetus and hemoglobin A too. But in hey, uh, single cell, you look for HBs. So this person has loads of HBs and, like, no hemoglobin A which is the main one in a normal person. And this test HPLC again, you don't need to know in detail at all waiting to see we're looking for hemoglobin s. That's the main point. Looking for hemoglobin s using these two methods. Okay, so the last condition and we have one more s be a is beta thalassemia. So it's two thalassemia is beaten it alpha, and it just depends if the Alpha chains are affected or the beta chains. And these chains are part of the globe, in which is in the hemoglobin, just to be just to be clear. So you get either reduced or lack of production of beta chains is inherited in an awesome a recessive pattern again. And you can have pizza thalassemia minor. So you only have your heterozygous only have one piece of thalassemia. Gene, you can have beta thalassemia intermedia. So you are symptomatic here, or you can be symptomatic. Sorry, you might have an anemia, so you might be tired and weak. Um, you might actually be homozygous. You might have to beta thalassemia genes, but usually there are some alleviating factor, which is going to be some clever genetic abnormality that's quite, uh, complex. But you have some alleviating factor. Um, but it's clear to understand that this beta thalassemia is non transfusion dependent. And then we have beta thalassemia, major. And the main thing about this is that transfusion dependent. So these patient's need transfusions to survive to live, so it's quite severe. It presents after around six months because up until then, you can use your, uh, your fetal hemoglobin to help you out. But after six months, you really need that hemoglobin A or adult hemoglobin to help you to have good hemoglobin. That's why it presents after six months. So you run out of the H B F. And then so you're dependent on transfusions. You need them to survive. It's really important. So then you need iron curation with the transfusion. And does anyone know why you need I Insulation? Yes, Organ overload causes organ failure Exactly. That's it. So it particularly can build up in your heart, causing heart failure in your liver, causing liver cirrhosis and in your pancreas causing diabetes. It's not Yeah, it's not great. And you need articulation to help you with that. That's really important. And you have that and then diagnosis against the same investigation as simple cells, the hemoglobin electrophoresis and H p R. C. But we're not looking for HBs. We're looking for an increase in another type of hemoglobin called HB A too. Um, and the way I like to think of it is that HB A is your normal one. Um and you're not making enough hb A. So you have to make more HBA to okay, It's quite complex. Why you have more HBA too. But just think of HBA to fallacy. Mia, have more of it and then have antenatal screening. So when the mother comes and she's, you know, pregnant, we can test for thalassemia and workouts. You'll have fallacy me and this can help. Okay, so our last s be a It's about sickle cell. Um, so, uh, Luisa, a g a 30 year old female with think cell anemia presents to a and e very unwell chest pain, breathlessness and fever observations. We will a temperature of 38.1 degree Celsius, a heart rate of 98 a respiratory of 24. And we do a chest x ray below. Um, so based on the traffic train, all these findings What is the most likely diagnosis? A plastic crisis? Acute chest syndrome, hemolytic crisis, pain crisis, sequestration, crisis. So these are all the crises that we see in sickle cell. And which one is she currently having? And we can look at the results of seeing us because we are over time. Sorry, guys. Okay. Oh, be. Yes. So we're currently okay, so I'll show you why it's bi so quite obvious because they have lots of chest in terms and you have a chest X ray. Uh, so in the chest X ray, they have, um, a classification in the right lower zone. Um, with acute chest syndrome, you can also get bilateral classification. That's probably the more SBA style answer. Um, SBA style extra with bilateral pacification. Um, but yes. And this patient has is very unwell. Um, and they have chest pain and breathlessness with acute stress syndrome. You can have, uh, an infection as well with it. And the patient's are really unwell. They need to be treated with analgesia for the chest pain and also things like blood transfusion for their anemia. Um, and need to be given things like antibiotics that they have an underlying infection, maybe a ct pa to look for a blood clot. But, yeah, they're very unwell. So a plastic crisis like hereditary spherocytosis. So I used a chess before, and I met hereditary spherocytosis iss. It's not great using acronyms if you're not clear. Sorry about that. So yes, Um, again, your blood, your bone marrow is not working because this parvovirus B 19, it's just it's just stopping a bone marrow from working, so you're very low hemoglobin and low reticular sites because your bone marrow is not working, humanistic crisis again can be triggered by think. Viral infection got low hemoglobin, but instead you get high reticular sites because your bone marrow is actually working to increase red blood cell production. Yet pain crisis when you you can have pain crisis in um, basically, when you have basic occlusion of your vessels, so it's gonna happen in any part of your body can happen in your knee and your elbow. This patient has chest syndrome, so that's leaning towards chest symptoms. So we're leaning towards acute chest syndrome and also the X ray. And the sequestration crisis is when your spleen gets full of these abnormal cells, Um, and then you get a really large spleen, and it's not that common. Um, but it's more common to have, like basic basic inclusion, your spleen and have loads of, um, in Fox. But Secretary in crisis, it's less common, Um, and that will present with splenomegaly. So, yeah, these are just all the crises you can get as well to other complications and civil Celik stroke. Yeah, Thank you for staying. Uh um, yeah. Thank you so much for staying. I'm sorry for the Internet and cutting out a few times. Um, please leave some feedback. Um, and I will make sure to send these slides to the right person. Something can be sent to you guys. Um, but yeah, I hope. I hope you find it useful, homes. Use it for your progress test. Um, and good luck for your progress test as well as someone asked. When do you study hematology in the in Cardiff. And you're meant to study it in third year. A little bit. That's when I did it, but yeah, oncology and surgery block. Yeah, hematology. You're You should do some. You should. You should. But what they actually do is another question. But I'm currently doing an indication hematology you can do as well, which is quite good. Um, yeah, and I hope all the questions were answered. Thank you guys for answering the questions as well along the way. Um, that's really helpful. Yeah, No worries. Thank you so much, Hannah. That was a really, really good, thorough, comprehensive talk, really good detail. And I'm sure everyone benefited Loads. Um I put the feedback in the chat. Sorry for the overrunning. Um, and our next session is a psychiatry. And that's this Thursday. Um, this coming Thursday. That's our last one of the series before the progress test. Yeah, thank you all so much. Thank you. Just wait for everyone to sleep like my leukemia or himself. So someone asked. And why Milo? Leukemia. Does Milo cells decrease in number? The Milo says in my lord leukemia should. So in chronic myeloid leukemia, the Milo cells do increase like the neutrophils increase. Those are my lord cells and lymphoblastic leukemia. The lymphocytes go up because it's a lymphocytic anemia. So sorry if I wasn't clear, but in my lord leukemias. So in acute myeloid leukemia, um, you get a pancytopenia because your bone marrow is just really bad. It's just not working, and it affects your earlier cells as well. So, um, it affects your milo blasts. So at that point, your bone marrow is not working well, you're not going to get really any good cells further along Mhm aml. Your bone marrow is just really bad. You get pancytopenia. It affects your early my lord cells in CML it affects your later my lord cells. So therefore, you see an increase in those cells that you get in your blood counts your neutrophils Arizona feels, um and that's why and then in, um, yeah, and then a lymphoblastic leukemia will get increasing lymphocytes. Good, uh