Final Year Series: Haematology

You, um, so hi guys. So I'm Rimer. Um, I'm an F1 doctor. Um, I'm currently working on hem-oncology at Barts Hospital in London. Um, and we've also got Amon on the call, who's just helping with any questions and, um, is sort of the lead of all of the final year stuff for Mind the Bleep. So, um, so yeah, um, thank you, Amon. And we'll just get started. So I'm going to give you guys a lecture on hematology today. Um, it's quite a complicated topic in general, and I remember at medical school finding it really confusing. So I'll try and make things as simple as possible, but obviously, um, just feel free to shout out with any questions that you have. Um, so in terms of the structure of the talk, so we're just going to go through a few different topics, um, as outlined over here. And then at the end, I've got some SBA questions. Um, I think there's just about five or six, and we'll go through those. Um, and it shouldn't be more than an hour, hopefully, but we'll see how things go. Um, so in terms of what we're going to cover today, today, um, I'm going to go through how to take a hematology history and examination. It doesn't tend to come up in OSCEs too much, um, but I think it's just important, um, to know how to do it in general because heems is a part of so many different specialties. Um, and then we'll go through some blood tests, how to identify, um, different sort of hematological disorders, including anemia, um, some of the malignancies, any coagulation disorders, etcetera. Um, and then the majority of the talk will be anemia because that's the sort of biggest thing in heems. Um, and we'll go through some high-yield things at the end, followed by SBAs. So, hope that's okay. So, um, if we just start with how to take a hematological history, um, it's important to just be aware that you may need to ask these questions in several different scenarios. So we'll go through how to do the history first. So in a heems history, it's always important to ask about any symptoms of anemia. Um, so this could be things like any shortness of breath, um, you know, generalized tiredness. Um, if they're really anemic and severe cases, then patients may often feel quite dizzy as well. Um, palpitations are super common because you've essentially got less blood being pumped around the body, so your heart has to work a little bit harder. Um, and then again, in very sort of severe anemia cases, patients can also get chest pain for very similar reasons in terms of your heart working extra hard. Um, and then obviously, we've got loads of different hematological malignancies. You've got the lymphomas, myomas, all the leukemias as well. Um, and all of them tend to, in one way or another, present with your B symptoms, as we call them. So that's things like night sweats, weight loss, um, fevers more than 38 degrees, um, and also any new lumps or bumps anywhere, so lymphadenopathy. So always really important to ask about those things as well. Um, and with weight loss, just remember to quantify exactly how much. So how many kilograms have they lost in the last three months or, um, in a year or whatever it may be. But yeah, really important to quantify that. Um, and then the other thing is symptoms of infection. So, um, in lots of different heems disorders, which we'll talk about, um, patients can often get either a low white cell count or a very high white cell count. But regardless, those can be, um, indicative of some sort of infection or bugs going around. So ask if, you know, in the last year, how many times have they been ill with coughs and colds and and things like that. Um, have they had any hospital admissions requiring antibiotics? Um, or, you know, how have they managed all of these infections, basically? Because it's a red flag if someone's had, um, it's, it's sort of an arbitrary number, but in, in heems, we don't like them to have any more than, um, an infection a month. So if you're having, you know, if you're ill two or three times a month for every single month of a year, um, then everyone tends to get quite worried about that. Um, so that's that. Bruising and bleeding. So, um, if your platelets are low, which again can happen in several disorders, then you might have a lot of bruising. You might have bleeds which can range anywhere from, you know, just epistaxis and any mucosal bleeds to something more severe like, um, bleeding into the joints or, you know, massive, um, hematomas, basically. Um, so those are the four main things to, to ask about, and those are the four main things that we worry about the most. Um, but obviously, just some other things to be aware of. So important to ask about their diet. So, um, that will be particularly important for any nutritional deficiencies. So, you know, like the classic sort of, do you eat green leafy vegetables for anemia? Um, are you vegan? Because if, if, you know, vegans can sometimes have a low B12. So, so yeah, um, just sort of general things like that. Um, and then drug history. So this is an interesting one, um, and I see it all the time on hem-oncology, um, but there are a lot of drugs that we actually give to patients with heems problems that can inadvertently also cause bone marrow suppression and therefore lower all of your counts. So your red cell count, your platelets, your neutrophils as well. Can you guys think of maybe if you just put it in the chat, any drugs that you know that might lower some of your counts and cause sort of pancytopenia? Don't worry if not, but just wondering if you know anything off the top of your heads. Um, yep, carbamazepine, that's a good one. Um, I'm not really sure if statins lower your counts. Maybe I've, I've never heard of it personally. Methotrexate, exactly. Clopidogrel. Yeah, you won't really see clopidogrel very much in, um, heems patients, um, but yeah, definitely in psychiatry patients. Um, the other one that I'm thinking of is co-trimoxazole. Um, so yeah, so the main, the main three that I would, I would say, be careful with methotrexate, carbamazepine, and co-trimoxazole. Um, and co-trimoxazole is often, um, something that we use to prevent people from getting infections as prophylaxis. So, um, and yeah, that I would say that's probably the commonest drug in heems. So just be careful with those. But yeah, um, excellent ideas. Not, I'm not sure about statins, but maybe. Um, so yeah, so that's that. And then in terms of family history, again, you don't have to spend very long on this, but just asking them if they, if they've got a family history of any hematological disorders. Um, they often won't know what that means, so maybe just wording it, um, in something like, you know, have you got any, um, blood disorders that run in the family, or has anyone been told that they've got anemia, etcetera? So, so yeah. Um, and the last thing is social history. So obviously, you'll ask this in any history that you take, um, but just some things to be aware of. So alcohol, um, or chronic alcohol abuse in large amounts can cause macrocytosis, and we'll talk about this more when I, when I speak about anemia. Um, and then the other thing is smoking, which can cause polycythemia, which is essentially just, um, a very high red cell count and hematocrit, um, level. So, yeah. Um, can I write it up, please? Do you mean the, um, different drugs? I can definitely send them around later, um, but if that's what you mean, just to reiterate the main ones that I was thinking of was Methotrexate, carbamazepine, and, um, co-trimoxazole as well. Fine. Um, Amon, maybe you just want to spell them in the chat, I don't know. Um, but yeah, I can definitely send them around later. No worries at all. Um, yeah, cool. So we'll go on to the next slide. Oh, and then travel. Malaria can often cause anemia as well. It's just asking if they've been abroad anywhere recently, especially if you've got a very well patient or you know someone who was previously very well and has suddenly come back from holiday, very unwell. So, yeah. So, um, that was the history. Now, just some things to sort of look out for in a, um, examination of a sort of hematological person, I guess. Um, we'll go through some of these things. I don't know if you guys can see my cursor, but if we just start with the image on the top left-hand corner, the one of the eyes. Um, any ideas what the main sort of finding is here? If you just put it in the chat again, or feel free to shout out as well. Yeah, fantastic. So jaundice. Um, fancy word for the eye, one for when it's in the eyes is, um, scleral icterus. Um, so someone said iron deficiency. Good idea, but if you look at the other picture of the eye, so the one that's second in the bottom row, um, that's more a sign of iron deficiency and anemia, and that's conjunctival pallor. Um, so you can see that the conjunctiva in that second eye photo in the bottom row, and the conjunctiva are very pale. Um, you'd expect them to be more sort of vascularized and and more red, basically, if you look at your own ones in the mirror. Um, so that would be anemia, conjunctival pallor. But yeah, the top left one was jaundice. Um, often seen in, um, hemolytic anemias. Um, obviously in, you know, gastro patients as well with with liver issues. Um, so yeah, so that's that. So if we now talk about the second photo from the top, so the one of the, again, I don't know if you can see my cursor, but the one of the red cheeks. Um, malar rash? Yeah, it does look like that actually. I don't blame you for saying that. Um, I don't know very much cardio, but yeah, it it does look like that. But in the context of a heems patient, what might you be worried about? Yeah, facial plethora. Um, so it is facial plethora. Um, you've got basically this, you know, bilateral redness of of the cheeks of this woman. Do we know what kind of conditions in heems can cause plethora, or one condition really? Yeah, ruddy cheeks is the other way they tend to describe it. Excellent. Yeah, polycythemia rubra vera. Excellent. So, yeah, so basically, um, we'll talk about polycythemia, but in polycythemia, you have an increased red blood cell mass. Um, and when you've got all of those extra sort of red blood cells and hematocrit, that causes, causes your blood to become a little bit thicker, and so you get all of this sort of swelling and vasodilation of all of your blood vessels, causing, um, that sort of complexion. And the other thing patients will often complain of with polycythemia is that this is, it can sometimes be very itchy as well. Um, and although I've showed a photo of the face here, you can pretty much get this kind of redness anywhere on the body. So it may be on their palms, on the soles of their feet, um, like rarely in their nails as well. So, yeah, excellent. Um, yeah, and then the photo right next to that, so the one of the lips, what are we seeing there? Yes, perfect. So, um, angular stomatitis, angular cheilitis. Um, I think the terms are interchangeable, but, um, yeah, either one of those. So you can see that on the sort of on the sides of the, um, lip, so where the top and bottom lip meet, you've got all of these, it's not a very good photo, but you've got cracks and fissuring of the skin and the mucosa on the inside of the mouth. So, um, yeah, and it's a sign of usually it's iron deficiency anemia, but sometimes you can also see it in B12 deficiency as well, and it's usually a sign of very severe, uncontrolled anemia that hasn't been treated for, um, months and months on end. Um, so, yeah, be very careful of that. And then the photo right next to it, um, I used to always get really confused at the difference between petechiae, purpura, and ecchymosis. So I've just put a photo on there to show you, and I know you can't really sort of measure it by eye, um, but just take my word for it. So the way to sort of identify the difference between the three is petechiae are usually very small and usually only anywhere between one to three millimeters, but no more than that. Um, if you've got multiple of those coalescing together, then you'll get purpura, which still look very blotchy, but, um, still sort of look like loads of separate different spots. Um, and and that's that's purpura. But then ecchymosis is where you basically get a massive bleed into the skin, um, and you can't really, you know, separate out all of the different lesions in there. It just looks like one big blob of red, basically. Um, and that's just a massive, massive bruise. Um, so, yeah, so that's the difference between those three. Um, and then the photo that I've got on the bottom left, so the, again, the one of lots of little tiny red spots, that's just another example of petechiae. Um, or at least I think it's petechiae. We don't know how big big they are, but I think they look small enough to be petechiae. Um, and I think that's around the knees. So those are most of the photos. If we just now look at at the one of the tongue, what are we seeing there? Any ideas? Cool. So, um, someone said leukoplakia. You're right, it could be leukoplakia actually, and I'm not too sure how you would differentiate that from from thrush. Um, so and and both leukoplakia and candida, you tend to get in very immunocompromised patients. Um, so it's a great thought. Um, but actually in this photo, um, well, when I Googled it, I was Googling photos of candida, oral thrush, basically. So, so that's what this particular image is. Um, and yeah, again, tends to happen in immunocompromised patients because we've got all of this flora living in our bodies, but it just overproliferates if you don't have any immune cells. Um, some people also said glossitis, smooth tongue. I do agree it looks a little bit smooth. They may have an element of anemia as well. Um, but yeah, and yeah, I think Amon just said hairy leukoplakia is typically on the side of the tongue. Ah, amazing, that's how you tell the difference. Um, so, yeah, and then the last photo, I think, um, is is more, is probably one of the most obvious ones, but we've got a swollen lymph node there, just underneath, um, in sort of the angle between the chin, um, and the neck, and it's probably, I mean, it's probably the super, one of the superficial cervical lymph nodes, but yeah, that's also quite concerning because you wouldn't expect lymph nodes that big just after a normal infection. Um, so good, excellent. Is glossitis enlarged tongue or smooth tongue? Um, it's smooth tongue, maybe both. But I think we usually refer to glossitis, meaning smooth tongue. And so if you've got iron deficiency, you'll have a very smooth tongue, but it won't be, you know, swollen or anything like that. But the opposite tends to happen in B12 deficiency. You usually get a very beefy red tongue, um, which you could, which sometimes can look a little bit enlarged. Um, so I guess it can mean both, just depends which, which type of glossitis you're speaking about. Um, but yeah, and yeah, petechiae are due to bleeding disorders, usually due to low platelets. So if you've not got enough platelets, then any small insult to your skin, you know, if you accidentally bash your arm against a door or something, then that will cause, um, sort of superficial bleeding because your capillaries just burst very easily. Good. Um, and then I won't spend too long on this slide, but there's not much to a hematological examination, but there are a few things to always, um, watch out for. So the main two things that I always think of is always examine the lymph nodes and always feel for the spleen as well. So if you've got splenomegaly, you can see in the top right picture, your spleen obviously sort of on the left-hand side of your body, but when it enlarges and when you've got splenomegaly, it tends to extend down towards your right iliac fossa. Um, so it's always important that if you're feeling for someone's spleen, just make sure you also feel down to the right iliac fossa and just to assess the sort of extent of enlargement. Um, and then sometimes you can get hepatomegaly as well, less common, but we do see it in patients. And, um, yeah, I mean, that would just be, you know, an enlargement under your sort of right ribs. Um, and then the lymph nodes, main thing to say about the lymph nodes is, um, we're most concerned about three areas, which is the lymph nodes in the neck, the lymph nodes in the, um, underarm, so in the axilla, and lymph nodes in the groin as well. So just have a system of of sort of feeling them all. Um, and I guess with the, the most complicated ones are the neck ones, really. And, um, the picture on the left is quite helpful, but just have a system when you're examining them. So start at the top and work your way down, or vice versa. Um, and never forget your supraclavicular lymph nodes as well. Okay, fine. So, um, just some differentials of all of our different examination findings. So with lymphadenopathy, obviously the commonest things that cause lymphadenopathy are infections. Um, so EBV, HIV, TB, a lot of vaccines, so the COVID vaccine, for example, can also cause lymphadenopathy. Um, so might be worth asking if they've had any recent immunizations. Um, and then some more uncommon causes are things like, or the more concerning things, really, so lymphomas, any other solid tumors that have metastasized to your lymph nodes. Um, so a bad, it's a bad sign, really. But in particular, your breast cancer tends to spread to your, um, axillary lymph nodes. It's just something to watch out for. And then probably the most rare one, but sometimes in inflammatory disorders like SLE, you can also get lymphadenopathy. But I've never really seen it or or heard about it to be honest. Um, so that's really lymphadenopathy. And then for splenomegaly, um, I think PM or somewhere else online used to say the three Ms are the commonest cause of splenomegaly. So those are, um, chronic myeloid leukemia, the myeloid being that M, and then myelofibrosis and malaria as well. So just good to memorize those three in case it ever comes up, in case you have a splenomegaly patient in OSCEs, you can sort of reel out those differentials. Um, and then just some, I've just listed some other causes on there. Um, so again, our, you know, lymphomas, leukemias, if they infiltrate into the spleen, can cause splenomegaly. Obviously, anything causing portal hypertension. Um, and then, yeah, a few other things on there as well. Um, and then hepatomegaly. So, um, again, a lot more sort of systemic causes for that. So right heart failure can cause hepatomegaly due to backflow. Um, again, liver issues, so, um, liver cancer or mets from any other type of cancer. Um, and then some, some of the rarer sort of genetic things like hemochromatosis, myeloproliferative disorders as well. Um, so someone's just asked, how are the erythematous features iatrogenically affected by treatment such as anticoagulants and antiplatelets? Um, do you mean can anticoagulants and antiplatelets cause the erythematous features? Um, I'm not too sure what you mean, but I mean, yeah, theoretically, anticoagulants, so things like heparin, can also lead to bleeding. Um, but obviously, we don't usually expect that. Um, and we'd be quite worried if it caused bleeding in someone. And also, um, I think with usually with things like anticoagulants, we're more worried about bigger bleeds and sort of systemic bleeding, so things like, um, cerebral bleeds and and bleeding everywhere else. Whereas when you've got low platelets, you get much sort of smaller bleeds, so things like all of your mucosal stuff, so like, you know, nosebleeds, bleeding into the gums, all the superficial stuff that I showed you photos of, like petechiae, purpura. Um, so that's one of the differences, I guess. Um, but I don't know if I interpreted your question correctly, so just let me know if if you meant something else. Um, but yeah, so let's just talk about the full blood count as well, very briefly. So, um, when we look at a full blood count in heems, there's three main things that we want to look at. First is the, um, Hb, so hemoglobin. Um, the neutrophil count as well, and also the lymphocyte count. And I've just sort of split it into, um, things that we, our differentials if if the counts are low, and our differentials if the counts are high. So, so, um, if we just start with hemoglobin, um, obviously if your hemoglobin is low, then we're worried about anemia. There's several different causes. I'll go through them, but if you notice a low hemoglobin, the key things to do are also check the MCV and request any, um, hematinics. So your hematinic, hematinics are basically ferritin, B12, and folate, um, because that will allow you to further differentiate what type of anemia you're dealing with. Um, but on the flip side, if your hemoglobin's high, um, then we worry about polycythemia. Um, and polycythemia is split into primary and secondary polycythemia. So primary is genetic polycythemia. Um, and you guys may or may not have heard of some sort of funky mutations that cause polycythemia vera, so things like the, um, JAK2 and CALR mutations, I think they are. Um, they tend to cause polycythemia vera. And I think JAK2 mutation is present in more than 95% of patients or something like that. So that's your sort of primary genetic, not a patient's fault or anything like that, basically. Um, secondary polycythemia is, um, not inherited, and there's several different causes. So we've got things like COPD and smoking. And in both of these, what happens is you've basically got chronic hypoxia to the lungs, and so in order for your body to deal with that, it just produces more, um, Hb and more hemoglobin, so that, you know, you've got enough being pumped around your body. So, so that's why you get polycythemia in those lung conditions. Um, and then sometimes, so with renal patients who are on erythropoietin because they don't make enough in their bodies, if you accidentally take too much of that or you prescribe too much of it, then again, your, your hemoglobin will be raised. High altitude is sort of similar to COPD and smoking. It's just, you know, for your body to adapt to low oxygen saturations at higher altitudes, you know, if you're going like mountain climbing or you live in the mountains or something, then again, your hemoglobin will be raised. Um, so, yeah, so that's sort of polycythemia in a nutshell. Um, I think I do have a slide on it later on as well. Um, but if we talk about the neutrophils now, so, um, if your neutrophils, neutrophils I find a little bit confusing because sometimes they can be low in infection, sometimes they're raised in infection. Um, so it's, it's all a bit confusing, but what I've been told is that if your neutrophils are low, then we tend to worry more about viral infections. Um, or the sort of non-viral infection that we tend to worry about is TB. Um, but if your neutrophils are high, then we're more concerned, it's almost always a bacterial infection, um, being the cause of of a raised neutrophil count. So low is viral, high is bacterial, is the sort of generalized rule. Um, but they can also be high after surgery, inflammation, um, etcetera. Um, the other thing is, so, um, some ethnic groups also, um, tend to just have low neutrophils or have a higher, um, sort of probability of having lower neutrophils, and it's fine, it's not worrying at all. Um, but I think it's Afro-Caribbean ethnicities in particular, just have hereditary, um, low neutrophils, but they're not concerning and we don't do anything about them. Um, so, yeah, and then drugs. So we already talked about some drugs that can lower our neutrophil counts earlier on, um, but but most chemotherapy regimens also lower your neutrophil count. Um, and that's why you get neutropenic sepsis, which I have a slide on later as well. So just to be aware, any patient on chemotherapy, always check their neutrophil count. Um, and then obviously some autoimmune conditions as well. Um, but yeah, and then just to talk about any, any neutro, any high neutrophil counts that you come across, obviously we talked about reactive neutrophilia. The other thing is, um, leukemias as well, can sometimes cause very high neutrophil counts. Steroids as well can sometimes cause a falsely raised neutrophil, and you'll get people being really worried about this patient has an infection because their neutrophils are super high, but actually it's just a reaction to the steroids. Um, and then obviously in some myeloproliferative disorders like, um, myeloleukemias, you can also get high neutrophils. Um, yeah, so those are your neutrophils. Then just moving on to the lymphocytes. So, um, again, sometimes after surgery or trauma, your lymphocytes can be a little bit low. Not really sure why, but, um, yeah. And then COVID-19, you guys may or may not remember, but again, um, typically patients would have low lymphocytes, and that would be a way to, um, you know, differentiate COVID versus another viral disease or bacterial infection, for example. Um, and obviously HIV, you get low CD4 lymphocytes. Um, and autoimmune disease. And then for high lymphocytes, annoyingly, again, viral, some viral infections can cause high lymphocytes, like EBV. Um, chronic things as well, like TB. And then any, uh, lymphoid malignancies that involve your lymphocytes, so the, um, lymphocytic leukemias, for example. Okay. Um, that's that. And then, oh, yeah, so just some, um, other things about, just some other things to be aware of with your hemoglobin. So sometimes if you get a low hemoglobin, it may be a false result because if the blood sort of coagulates, then you may get, um, the sorry, this is not supposed to have hemoglobin, that's supposed to have platelets in the left-hand side. Um, so ignore that, that's my fault. So it should, so we're talking about basically causes of low platelets and causes of high platelets. Um, so if we just start with causes of low platelets, um, sometimes it's just a false result. So if you get platelet clumping, then your platelets will appear low, and the way to basically differentiate that is you need to get a blood film because if you get a blood film and it's worth just Googling this if, if you've got a computer next to you, but, um, on a blood film, you can see loads of platelets stacked on top of each other, basically, and that tells you that you've got a falsely low, uh, platelet count. Um, and then other causes include, um, your marrow, bone marrow, basically not producing enough platelets. So that can be in like aplastic anemia, where everything will be low. Chemotherapies, leukemias as well. Um, and then obviously either our marrow's not producing enough platelets, or, um, our platelets are being destroyed somewhere in the body. So, um, it can be due to immune causes like ITP, infections as well. Um, you know, DIC, drug reactions, drug-induced thrombocytopenia, sorry, drug-induced, um, thrombocytopenia from things like heparin. Um, and, yeah, and then the other reason is splenomegaly. So sometimes, um, if you've got splenomegaly, all of your platelets might pool in the spleen and basically get destroyed. So that will cause a low platelet count as well. Um, and then for a high platelet count, so again, it could be reactive to several different things. Sometimes if you've got a patient with iron deficiency anemia, you might see that their platelets are also raised, and it's just a reaction. Not really sure why, but those two things sometimes go hand in hand. Um, and then obviously to things like infection, surgeries, malignancies, etcetera. Um, and a bit like polycythemia, we've also got essential thrombocythemia, which is raised platelets. It's a myeloproliferative disorder. Um, and, yeah, those are the sort of main causes. And, yeah, just to reiterate, it should say platelets in that first column, not hemoglobin. Cool. And then I've just got a question in the chat. So how do you actually differentiate bacterial versus viral infections? Is it just fever and bacterial? Any other sign such as sputum volume or culture? Um, so usually, um, so I'm working on hematology, and usually, to be honest, it's based on all of the investigations you do. So obviously, you'll send, if if a patient's got a fever or they're spiking, you know, they're spiking a temperature, they're unwell, you would send off blood cultures, which may grow some sort of bacterial bug. Um, and you'll be told if it's gram-negative, gram-positive, etcetera, and in that case, you'll know they've got a bacterial infection. And usually, as part of the septic screen, so you'll do your blood cultures, you'll also send off a respiratory viral swab, or if they're coughing, then you might do a sputum sample and send that off for MC&S, and and that would also tell you whether, you know, they've got any bugs growing in their sputum or or if any of their viral swab results come back as positive, then yeah, you'll know if they've got a viral infection. Um, I think generally, I remember often at medical school, yeah, so you're right about the sputum color. Yeah, the procalcitonin is a really good point. So if you've got a raised procalcitonin, that tends to be a sign of a bacterial infection as well. Um, and so you were asking about symptoms and signs, so yeah, I, I know at like medical school or generally people think that if you've got green sputum or yellow sputum, then that's a sign of a bacterial infection. In real life, or like with patients, I've not really found that to be helpful. Everyone pretty much has yellow sputum. Um, so but yeah, theoretically, yeah, you should, and you should definitely ask about the color of their sputum, and if it's like green, then you're more worried. But light yellow or yellow sputum, I wouldn't be, I wouldn't rely on it necessarily. Um, and yeah, and I don't, I think there's not much else really. Sometimes the severity, you know, viral infections can be a bit milder, like, you know, rhinovirus is just a mild sort of cough and cold, whereas bacterial infections can be a little bit more serious and cause sepsis and bacteremia. So, so yeah, but yeah, don't think there's much else I can think of there. Um, but yeah, so I've just got a slide here on how to approach anemia. Um, so I think it's important to just understand what's going on with our red blood cells in order to understand what then happens in anemia. So I won't spend long on this, but basically, our red blood cells go through several stages both in the bone marrow and the blood as well. So initially, all of your red blood cells are pluripotent hematopoietic stem cells, which means they can basically become a absolutely anything that they want. You know, they can become platelets, red blood cells, white blood cells, etcetera. And then eventually, after some time and some cool complicated things happen, they basically become reticulocytes, and your bone marrow will throw out a load of these reticulocytes, which are basically immature red blood cells. And they don't tend to spend any longer than a day in your blood. But if you ever get a blood film, you'll often be able to see a few of these reticulocytes because every day some of them will be thrown out of your bone marrow into your blood. Then once you've got your reticulocytes, after that, after a day or so, they will then turn into erythrocytes, which are your mature red blood cells, and these have a lifespan of about 120 days in your blood, after which they're destroyed, um, in the spleen. And then I've just got a photo just to remind you guys of, or to remind myself as well, really. This is what a hemoglobin molecule looks like. So you've got your two alpha chains, your two beta chains, and then your heme molecule in the middle as well with iron atoms. Okay. Um, fine, cool. So what can actually go wrong to cause anemia? There's three main things, really. So either you're losing blood from somewhere. Again, many things, so cancers causing GI bleeds, or ulcers causing GI bleeds, trauma, surgery, heavy periods. Um, or you're not producing, um, enough red blood cells. We'll talk about what causes that. Um, or you are producing red blood cells, but they're just very frequently being destroyed and aren't actually lasting in your system for 120 days. Um, yeah, and then this is just a nice schematic to show you causes of sort of decreased production and increased destruction of your red blood cells. So if we just start with the left-hand side, so things that cause decreased, um, production. So you've got your nutritional deficiencies that can be iron, B12, folate, as well. Um, and then also reduced bone marrow. So if you get bone marrow infiltration with things like leukemia and lots of white blood cells, then that basically stops your bone marrow from being able to produce all the other cell lines. So you might get low platelets, low red blood cells, but obviously have a very high white blood cell count because of the leukemia. Um, and then sometimes when you've got a lot of inflammation in your body, um, or in genetic disorders like thalassemia, you do get red blood cells being formed, but they're just not formed in the correct, um, way necessarily, or with the correct amount of alpha chains and beta chains. So there's that as well. Um, and then if we talk about increased destruction, um, so which, which is also called hemolysis, we split that into intrinsic and extrinsic issues. So intrinsic issues are usually, um, problems with the actual red blood cells themselves. So they're either not the right shape, or they're not working properly, or there's a problem with the hemoglobin, for example. Um, and usually most of these tend to be inherited disorders. So again, I've split them up. So if you've got problems with the metabolism of red blood cells, so that's things like G6PD deficiency, then again, you might get, um, lower counts. Um, and in G6PD deficiency, for example, you get an inability of your red blood cells to respond to hypoxia, and so they, they basically get destroyed, um, under oxidative oxidative stress. So there's that. And then problems with the red blood cell membrane, so all these funky disorders like hereditary spherocytosis, where the red blood cells are very spherical shaped, or elliptocytosis as well. Um, and elliptocytosis is rarer than the other one. Um, and then obviously we've sort of touched on the hemoglobin disorders as well, so thalassemia or sickle cell, where your red blood cells are just shaped incorrectly, and so again, tend to clog up in your blood vessels or get destroyed very easily as well. So that's the problems with the actual red blood cells themselves. If we've got, um, problems outside of the red blood cells, so that's usually, um, either problems with the marrow or, um, anything that we do to the patient, like transfusions, then again, we can get low counts. So, um, in autoimmune hemolytic anemia, you often, that's what AIHA is, you can get antibodies against your red blood cells attacking them, so they get destroyed very easily. And again, if you get, um, you know, incompatible transfusion reactions, which are very serious, then again, your red blood cells will become very destroyed very quickly. Um, and then also, um, we've got TTP and DIC, which can basically, um, cause sort of mechanical trauma to your red blood cells and cause your red blood cells to just shear within your blood vessels and and get destroyed. Um, so, yeah, and then, um, this is probably one of the most important slides of the, of the whole talk. So, um, if you remember back to, I said when you look at your hemoglobin, to, hemoglobin level, you want to check your MCV as well if you've got a low hemoglobin. So, um, we get low, normal, and high MCVs. Um, and so of course, causes of a low MCV, so usually this is iron deficiency anemia or thalassemia as well. Um, and sometimes anemia of chronic disease, but anemia of chronic disease tends to usually cause a normocytic anemia, so a normal MCV. Um, and then I've also put some rarer causes on there, which you don't really need to know about, but just good to be aware of for SBAs, so things like lead poisoning, CID, blastic anemia, and hookworm as well. So those are causes of low MCV. Um, and then if you've got a normal MCV, then the commonest one usually is anemia of chronic disease. So that may be due to renal disease or inflammation anywhere else in the body. Myeloma as well, for example. Um, so, yeah, and then also acute blood loss from anywhere in the body. Increased plasma volume, so if you're pregnant or you've got a lot of fluid overload, then your red blood cells will just get diluted, basically. That can cause a normocytic anemia. And then sometimes, um, if you've got a patient who's just deficient in all of their nutrients, and if they've got a low iron, which causes a low MCV, as well as a low B12, which tends to cause a high MCV, then those will sort of balance out and give you a normocytic, um, normocytic anemia with a normal MCV. Um, and then hemolysis as well. Um, and then causes of a high MCV, so that's the other end of it. So that, that's your B12, folate deficiencies, alcohol or any sort of liver disease, um, and hypothyroidism is, is the other sort of main one. Um, so, yeah, and unfortunately, it's something you just have to memorize at some point. It may come up in OSCEs, you may get a full blood count given to you, and you have to sort of talk through your differentials of what it could be, really. Um, and then the other thing that, um, I never really understood at medical school, but, um, that people tend to look at a lot is the reticulocyte count. So if you remember, I said reticulocytes are your immature red blood cells, the ones that only last in the system in your blood for about a day. So if you've got low reticulocytes, it means that your bone marrow is not producing, not throwing out enough of these reticulocytes, and basically, it's not able to make enough new cells to then send into your blood. So with low retics, always think that you have a bone marrow issue going on. But on the flip side, if you've got a high number of reticulocytes with an anemia, then it means that your bone marrow is working because it's sending out, it's, you know, pumping out all of these immature red blood cells. But the problem is happening somewhere outside the bone marrow. So the red blood cells are being produced, um, but either they're being destroyed, or you're losing them through bleeding, etcetera, etcetera. So, yeah, and then just to go into the different types of, um, anemia. So obviously, the commonest type of anemia is iron deficiency anemia, and it's important to not just, you know, label a patient with iron deficiency anemia. We need to actually figure out what the cause of it is, because there are just so many different things. And often, with depending on the gender of the patient and depending on the age of the patient, you'll be more suspicious about sort of different things. So if it's a woman, always ask about, um, heavy periods, so menorrhagia, basically. Um, or, you know, they may have stuff like fibroids, which can cause a lot of bleeding, and therefore cause iron deficiency anemia. But if you've got, say, an older patient or a patient who's come in with with other red flag symptoms like weight loss, night sweats, fevers, then be more worried about possibly a malignancy or a GI ulcer that's been chronically bleeding, or just sort of general chronic blood loss from from anywhere else. Okay. Um, and obviously, in relation to all of that, make sure you ask about any blood in the stool and the color of their stools as well, because black stools were thinking melena from an upper GI bleed. Um, and then just some other causes. So I told you about pregnancy causing dilutional anemia, malabsorption, so celiac disease, H. pylori. Um, and, yeah, just a couple of other things on there. Um, and in terms of your, uh, test results, again, people sometimes find this quite confusing, but ferritin is basically the stores of iron in your body. So someone just said you have to leave. Yeah, so our, our whole, this whole lecture is going to be recorded and then eventually put on either YouTube or be available on MedAll, so don't worry, you'll, you'll be able to access them. Um, but thank you for coming. Um, um, so, yeah, so ferritin is a store of iron in your body. So obviously, if you've got low iron, you'll have low stores of iron, therefore causing a low, low ferritin. Um, and then transferrin is what basically binds to iron in the body. So, um, if you've not got enough iron because of a deficiency, there won't be any of it, or very little of it, basically bound to transferrin, so the amount of transferrin that's saturated with iron will be low, if that makes sense. Um, um, and then serum iron will be low because obviously you don't have any of it. But TIBC, which is your total iron binding capacity, that will be high because it's sort of the opposite of transferrin saturation. It it sort of means that there is a lot of capacity for, um, for the transferrin to bind the iron, because not much of it is bound at the moment, so that's why that's high. Um, but yeah, I hope I didn't confuse that too much. Um, and then the treatment. So several different ways you can replace iron. The commonest in the community is oral iron. We usually give that as either ferrous fumarate or ferrous sulfate. These oral iron tablets tend to have a lot of side effects, in particular GI side effects, and that should say nausea, not nausea. But yeah, people tend to get either constipated or have diarrhea, can often feel quite sick with it. And we tend, we used to give people, um, a tablet three times a day, but most trusts have now moved to saying that one tablet a day is sufficient, because that's just much better tolerated in terms of the the GI side effects. Um, and then, and also people tend to tolerate fumarate better than sulfate, but fumarate is more expensive, which is why people sometimes won't be happy to give it. Um, and then, yeah, it's recommended to take it, take these tablets with vitamin C because that increases the absorption of iron. But avoid tea and coffee around the times that you take your iron tablets because they can decrease, um, the absorption. So that's just good advice to give patients. You could get an OSCE asking you to explain to a patient how to take their iron tablets, so important to say those things. Um, and then it's much rarer, but sometimes if someone's got really low iron and they're not able to absorb oral iron, so maybe they've got celiac disease or they've had bowel resection, for example, then we could give them IV iron. But it tends to not be very well tolerated, and you just have to be very careful around giving it. Lots of people also react to IV iron, so they have to be very closely monitored. Um, and then obviously in very severe cases, so on my ward, for example, where we've got all of these hematological malignancies, patients tend to be very pancytopenic, so get daily, um, blood transfusions to replace, to replace the, you know, low hemoglobin basically. Couple of questions. So, um, transferrin, could you explain the transferrin saturation again? Yeah, sorry. So basically, transferrin, um, binds to iron in your body. So if you've not got much iron in your body, it's not really going to be bound to the transferrin, so your transferrin is going to be basically very free to bind to loads of iron. Um, so that's why the amount of transferrin that's saturated with iron is going to be low because you don't have iron, if that makes sense. But just let me know if that's confusing. [Music] Um, yeah, and then the next question, so are both fumarate and sulfate available on the NHS? Do you ever need to give a pro? So, yeah, they're both available on the NHS. It's just sulfate's cheaper. So, um, most GPs and initially in hospital, we tend to try sulfate. Um, and if that doesn't work, then we can move, we can try fumarate instead. And then do you ever tend to

Give a prophy prophylactic laxative? No, never. Never really, really, um, because, I mean, I don't know the exact numbers, but I think diarrhea is probably equally as common as constipation. So, you, you don't know which way the patient's going to go, basically. So there's no point.

Um, and T, as far as I've seen patients, I think one tablet a day is okay for most people and tends to reduce the side effects significantly. So they don't usually tend to need anything. Um, or sometimes people recommend the other common regime I've seen is one tablet every other day. Um, so, yeah.

Um, what, and the other question was, what about iron deficiency with a normal hemoglobin? Have I talked? Is that it's not really in my talk. Um, good point. I should have probably included a slide on that. Um, but if I just go back to the causes, um, oh, sorry, never mind. I misunderstood your question. Iron deficiency with a normal hemoglobin, I've never really seen that, to be honest. Maybe Aman can help out with that. Um, but, yeah, I've never really seen an iron deficiency with a low normal hemoglobin. Um, I mean, if it's very mild iron deficiency, then maybe you'd have a normal hemoglobin, and we wouldn't really treat that. Um, we tend to get more, what, what sort of happens is that a patient comes in very tired or whatever, and you do a full blood count initially, you notice that they've got an anemia, and only after, after that, do you send off, um, hematinics, so iron levels, uh, folate, B12, etc. So usually, it's, you know, we're triggered by low hemoglobin and then find out that the patient has iron deficiency. Um, so, yeah, I've, I've never really come across it the other way around, but that's interesting.

Um, so the next thing to talk about is, um, megaloblastic anemia. Um, so that's where you've got a high MCV.

[Music]

And, okay. Um, sorry, I was just reading the chat. Interesting stuff. Um, so, yeah, so megaloblastic anemia. Um, and what we, what we mean by this term is you've basically got, um, a, a delayed maturation of the nu, nucleus of your red blood cells, and that's because you've not got enough DNA being made. And there's two main reasons for why, um, we've not got enough DNA being made for our red blood cells: either your B12 levels are very low, or your folate levels are low, and I'll talk about that in a second. Um, but basically, what happens when you've got these, you know, um, defective red blood cells, basically, is that they, um, get a very reduced survival time. They're just not able to be present in the system for as long a period of time. And what you will see on a film, and I think I've got an example of this on the next slide, is you'll get these very large red blood cells because the MCV is big. Um, and you'll often see multi-lobed neutrophils, which are basically just immature neutrophils, um, within the circulation.

So splitting it up into B12 and folate deficiency. So, um, B12 is absorbed in your terminal ileum, which is why some patients with Crohn's disease, as well, will have low B12 levels. Um, but the sort of classic cause that you may see in SBAs is, um, pernicious anemia, where you get antibodies against your parietal cells, so they don't produce enough intrinsic factor, and we need intrinsic factor to bind to B12 in order for it to be absorbed in your terminal ileum. Um, so that's the sort of main cause of B12 deficiency to remember, alongside, obviously, um, you know, nutritional intake and being vegan, for example, or not having enough, um, as is in the photo, not having enough sort of eggs, meat, dairy products, etc. Um, and then if you've got very severe cases of B12 deficiency, very rarely, you can get neurological symptoms. Um, so, you know, you'll often hear about subacute combined degeneration of the spinal cord, um, which is where you basically get, um, your dorsal columns, uh, undergo demyelination, and that can cause a range of neurological symptoms, so things like unsteady gait, loss of proprioception, etc. Um, and then we've talked about malabsorption, so Crohn's, gastrectomies, um, etc. And then, uh, folate. So, main source of folate is your green leafy vegetables. Um, and folate is absorbed in your, um, in the, in the upper part of your, um, abdomen, so the duodenum and the, um, jejunum. So again, any issues with those, then you may have folate deficiencies. And then the key thing is, if you've got a patient who's got both B12 and folate deficiency, um, always give the B12 before folate, not the other way around, because you can then, um, you may trigger the whole sort of subacute degeneration of spinal cord. Um, and that sometimes comes up in SBAs, actually. Um, and then causes, so dietary malabsorption, we've said. And treatment for folate deficiency is folic acid, 5 milligrams once a day. Um, I should have put it on here, but for B12 deficiency, um, usually depending on how severe it is, we either give oral B12 supplements, or in more severe cases, especially if they've got neurological symptoms, then we will give, um, injections of B12 as well. And then this is just a blood film, very briefly, to show you what, um, mega, megaloblasts look like. So these are the, these huge red blood cells that you can see. They're very big. Um, and, you know, we'd expect them to be a lot smaller. And then in the top right-hand corner, you've got a, um, hypersegmented neutrophil, so multi-lobed neutrophil, um, and that's what it tends to look like.

Okay. Um, and, yeah, someone just asked, but we'll just, um, sorry, we're running quite behind, but, um, here's a, here's just a slide for feedback. If we could just pause for a couple of minutes, you guys could just fill the feedback, we'd be really grateful. Um, takes no longer than a couple of minutes, and it's just really helpful for us to, um, plan our future sessions and sort of see what went well, what didn't go well, etc. So I'll just pause here for, for a bit. And there's just a question in the chat: Can chronic use of PPI lead to B12 deficiency? Um, you're, I think it's not very well studied, but you're right, there are some cases of, um, PPI use or high-dose PPI use leading to B12 deficiency. Um, we actually had a patient recently who had a, a low B12 that just wasn't improving, and then we found out that this patient had been taking, um, lots of omeprazole without us knowing, basically, from wherever they sourced it from. So, and in that case, yeah, we basically stopped the, the PPI, but the B12 didn't really come up. So questionable, but there's definitely, um, a sort of link that people have written lots about.

Okay, so I'm just going to power on in the interests of time. Um, so let's just talk about hemolysis. So, um, hemolysis basically means a destruction of red blood cells. Um, obviously, it's, it's not normal, we don't expect this to happen. And we tend to split hemolysis up into intravascular, so red blood cells breaking down within your blood vessels, and extravascular, that's, um, red blood cells breaking down in your other organs, so your spleen, um, or your liver as well. Um, the main symptoms to watch out for with hemolysis are, um, jaundice. Um, reason being, when your red blood cells break down, you get a release of lots of bilirubin as a breakdown product. Um, and that then basically causes jaundice. Um, splenomegaly happens because when your red blood cells, um, are being destroyed, they will basically sequester in the spleen in order to be then removed from the, um, from your system. Um, and then, so in, on the image on the right, um, I've got an example of a child who, um, probably has thalassemia, but you can see they've got a, they've got a lot of frontal, they've got what we call frontal bossing, so the forehead's just sort of enlarged and protruding forward. Um, and the reason for that is because they've got chronic hemolysis, and their red blood cells are breaking down very often. Their bone marrow's working extra hard to then produce more red blood cells, and your bone marrow basically enlarges, and that can cause all these skeletal abnormalities, um, as well. So, so, yeah. Um, and then it's hemolysis usually gives you a normocytic anemia, um, with raised reticulocytes, because the problem is not with your bone marrow. Your bone marrow is working fantastically, which is why it's enlarging and giving you skeletal issues. Raised bilirubin and raised LDH as well. Um, the other blood to look out for is haptoglobin. So haptoglobin is basically a molecule that binds to any free hemoglobin in your plasma. So if you're having a lot of hemolysis, you'll have a lot of free hemoglobin in your plasma because it's being released from your red blood cells. So all of that will bind to your hemoglobin, sorry, will bind to your haptoglobin, and then your haptoglobin levels will decrease, um, because they're all being occupied with all hemoglobin, basically. Um, and the other key thing is the direct antiglobulin test. Um, so we often do this when we're suspecting autoimmune hemolytic anemia, and the DAT test basically detects antibodies on your red blood cells, showing us that, um, you know, yes, they've been marked for destruction, um, and we've got an autoimmune process going on. Um, yeah, sorry. So someone just said, can you show us the slide of the megaloblastic anemia? So here it is. Um, and the main points were really just, you get these really enlarged red blood cells. Um, again, I, I should have put a picture next to it to compare to normal red blood cell sizes, but just take my word for it, these red blood cells are very, very, very big. Um, and just very sort of perfectly circular, um, which, which isn't normal. And then you've also got a hypersensitive neutrophil, so multi-lobed neutrophil in the top right-hand corner, um, which again, is a sign of megaloblastic anemia.

Oh, sorry, before that. Um, yeah, did you want me to talk about anything in particular, or did you just want to see the [Music] slide? I might just pop it back up at the end, um, if we've got time, just, just because I'm worried that it's 8:00 and everyone probably wants to, um, have dinner or something. So just remind me, but I'll put the slide back up at the end in case you wanted to read over it or ask me any questions.

Uh, um, so, yeah, so, um, next slide. So just wanted to speak about clotting very briefly. Oh, you just wanted to see the slide? Fine. Um, so, so, yeah, so clotting. So there's two main things to think about with clotting. Um, so we have what we call sort of primary hemostasis, and then you get secondary hemostasis as well. Um, and if you just look at the picture on the right, so what happens essentially is when you get injury to a blood vessel, your blood vessel will vasoconstrict, um, to, you know, stop anything getting to it. And then you'll get loads of platelets being attracted to the site as well. Um, they all clump together to form a platelet plug and basically block off whatever defect was, um, made in the blood vessel. And this whole process of vasoconstriction and a platelet plug being formed is what we call, um, primary hemostasis, basically. Um, once that's happened, so once you've got your platelet plug formed, um, you'll then get various sort of clotting factors being, and, you know, all part of the coagulation cascade, also being attracted to the, to the site of platelet plug formation. Um, and this is what we call secondary hemostasis. So secondary hemostasis is that whole sort of coagulation cascade that you may or may not remember from, from preclinical years. So with our clotting disorders, it's just important to think about it in terms of, is this a problem with primary hemostasis clotting, or is it a problem with secondary hemostasis? Um, so, yeah, and just next slide again. I'm not going to spend very long on this because, um, it's very preclinical thing, but just to remind you guys, um, the coagulation cascade. So we have the extrinsic pathway, which is measured by the prothrombin time, so PT, and really to be on, we use the INR. Um, and the intrinsic pathway as well, which we measure using APTT. And eventually, these two pathways basically converge, um, to, um, form the clot, which is, which is where you get fibrin formed right at the end from fibrinogen. Um, so, yeah, but I won't go over the numbers, but just useful to, to recap. And main thing is, remember extrinsic pathway, prothrombin time, intrinsic pathway, APTT.

So, um, with abnormal clotting, to think about what's sort of causing your abnormal clotting, we need to think about what the APTT and the PT is. So if you get a very long, prolonged, um, APTT, we're thinking about things like, um, heparin, um, hemophilia, as well, um, Von Willebrand's disease, because that, um, involves factor eight, and then just a few other things on there as well, like DIC, liver disease, vitamin K deficiency. And, um, if you sort of really look into all of these, um, different diseases, so with things like hemophilia, um, A, hemophilia B, etc., you'll, you'll realize that basically one of the factors in the intrinsic pathway will be going wrong, and therefore causing a prolonged APTT. Um, and then it's just the opposite for prolonged PT. Um, warfarin can sometimes, um, cause both, um, as can vitamin K deficiency, as can liver disease, because they just sort of cause a generalized effect on the whole coagulation cascade. Um, so, yeah, again, like I, it's very difficult to sort of memorize these and learn these, but if it helps, just think back to what factors are actually involved in each of these diseases.

And then when we're thinking about thrombosis, so abnormal clotting, basically causing things like DVTs, PEs, um, main thing to remember is Virchow's triad, which is this sort of triangle on the right. Three main things that contribute to excessive clots in the body: so stasis of blood flow, any injury to the endothelium of blood vessels, and also hypercoagulability. Um, and obviously, um, sometimes in an OSCE, for example, you may get a VTE risk assessment, or you may get a patient who's presented with DVT or a PE, and it's always important to ask for any risk factors of thrombosis, um, which are all of these things on, on the left-hand side: so age, the older you are, the more likely you are to get a clot, immobility, which is why all of our hospital inpatients are on prophylaxis, prophylactic, rather, low molecular weight heparin, and then all these other risk factors like obesity, pregnancy, malignancy, flights, as well, to ask for.

Okay. And then thrombophilia. So, um, usually when you get, um, a patient who's had clots like DVTs or PEs, um, in nine times out of ten people, it's not due to an inherited thrombophilia, and it's usually just because of one of the risk factors listed on the previous page. Um, but sometimes, if you're in a bit of a, um, more nuanced situation, so you've got a younger patient, and, and sort of arbitrary figure we use as someone less than 40, or someone's just getting loads of recurrent clots, or they've got clots in a really sort of unusual site, like the brain, um, or the spleen, for example, then you want to think about whether they've got something inherited. Um, it's always good to check for the full blood count as well, because, um, our myeloproliferative disorders, so things like polycythemia, thrombocytosis, they cause our blood to become very sticky, um, and can also, um, cause, you know, if your blood's sticky, that can cause clots as well. So just exclude those conditions. Um, but after that, the commonest inherited disorder is Factor V Leiden. Um, and basically, if you've got this inherited condition, it causes protein C resistance. Um, and again, you may or may not remember, but protein C and S are important in fibrinolysis, so breaking down any clots in our body. So if we don't have these proteins, then our clots can't be broken down, therefore, you know, you get clots, basically. Um, so, yeah, and then I've just, I'm not going to go through them all, but I've just listed some other inherited, sort of thrombophilias here, but main one to remember is Factor V Leiden. Um, yeah, and then, yeah.

So the other big topic in hematology is, um, transfusions. Um, so, and, and the main thing to remember with transfusions, really, is the types of reactions that patients have. So again, we've just got, um, five different ones on here, but if we just start with hemolytic transfusion reactions, so these are a never event. They're very, very serious. You hopefully will never see one because it, it just never happens, or shouldn't happen. Um, but it's basically where we give the wrong blood to, um, the, you know, the patient, or, or, you know, patients accidentally receive each other's blood, for example, but it's very bad. Um, and you'll see this reaction happen immediately, so within minutes, patients will present with things like, um, vomiting, headaches, chest pain, shortness of breath. Um, and also, they will, in most cases, be hemodynamically very unstable. So their obs will be completely off. Um, they'll be tachycardic, hypotensive, be spiking temperatures. So, yeah, it's, it's a very acute situation. And to manage it, obviously, the most important thing is immediately stop the transfusion. Um, you need to inform the laboratory, the transfusion lab, um, and the hematology lab of what's happened, and check the ID of the patient, and just make sure that you, or whoever, hasn't actually given the wrong, um, blood. Um, and then obviously get IV access, fluids, and bloods are very important. Um, and then because they most probably, they will be, um, their sats will be low, you want to give them oxygen. Um, and obviously escalate and get your seniors involved as soon as possible. Um, but main thing to remember is stop the transfusion.

Um, and then you can also get what we call non-hemolytic transfusion reactions. Um, so these are basically where patients do get fevers, um, after starting a transfusion, but they won't really be hemodynamically unstable. So you won't get a low blood pressure, um, you know, tachycardia, um, etc., or at least it won't be as severe. Um, and they're usually caused by antibodies in the recipient's blood, reacting to the blood that's being, being given to them. Um, it's nowhere near as serious. We can manage it by just slowing the rate of the transfusion. So usually we give one unit of red blood cells over two hours. So I would just slow it down to one unit over four hours or five hours, for example. Um, and obviously, to manage their fevers, just give them some paracetamol. Um, so, yeah.

And then the other common one, which is probably the commonest reaction we get to red blood cells, is an allergic reaction. Um, which can be sort of very variable. People, patients might just get a bit of a rash or, uh, urticaria, um, or on the flip side, they may, um, get anaphylaxis to the red blood cells, which is again, very rare. Um, it's more common to just have a bit of a rash, um, which if mild, you can treat with, um, steroids, so hydrocortisone, chlorphenamine, as well. Um, sometimes, um, our patients are just prescribed these things prophylactically anyway, in case they react, um, on the, on the PRN side of the drug chart. Um, and obviously, yeah, again, slow down or stop the reaction at the transfusion for a period of time. And then anaphylaxis, I'm sure you all know how to manage adrenaline. Um, and obviously with anaphylaxis, you should stop the transfusion as well.

Um, and then we've got two very similar things, so we get TACO and TRALI. Um, so TACO, um, tends to basically happen in patients who've already got a problem with the heart. So, um, they may have heart failure, for example, or something else, and it presents very similarly, um, to pulmonary edema. So you might get bibasal crackles, um, peripheral edema, you know, in the hands and feet, shortness of breath, etc. Um, and also hypertension. So I'll, I'll talk about TRALI in a second, but the main way to basically tell the difference between whether you've got TACO or TRALI is that in TACO, you'll have a very hypertensive patient, whereas in TRALI, you should have either a normotensive or sometimes a hypotensive patient. Um, but with TACO, um, they're overloaded, so we want to slow the transfusion down. And with our heart failure patients, we get, we prescribe them the unit of blood much slower anyway, so about four, over four hours. Um, and obviously consider oxygen and furosemide is often given with the actual red blood cells, so it will run at the same time, um, as well as afterwards. Um, if someone's having multiple transfusions, sometimes we just have a rule of furosemide with every other unit of blood, for example.

Um, and then TRALI. So TRALI presents a lot like acute, um, respiratory distress syndrome. Um, tends to come on a little bit slower than, um, TACO. Um, and again, does have very similar symptoms, so respiratory distress, hypoxia, pulmonary infiltrates. Um, but, um, like I said, their blood pressure will be either normal or low, and they may have a fever as well. And in terms of managing it, so same as TACO, stop the transfusion. Um, we don't slow it down, we tend to just stop it, give them oxygen as needed, and escalate. I would escalate with any of these things as an F1, um, but, yeah.

And then, um, just a quick, so I'm not going to spend too long on neutropenic sepsis because it was covered, um, in the oncology talk that I gave a couple of weeks ago, but essentially, um, very important in hematology, it's the main, um, oncological emergency, as well as hematological emergency. Um, and usually we're just referring to a neutrophil count. People have different cutoffs, but sometimes it's less than 0.5, sometimes less than one. Um, and alongside that, you'll also have either a raised temperature or, um, other signs of sepsis. Patients won't always have a raised temperature because if you're immunosuppressed, then you've not really got the sort of immune cells to actually produce the temperature. So, um, it, we basically say neutropenia as well as either a fever or any clinical sort of indications of sepsis. Um, so were different risk factors, as I've listed there, with signs and symptoms. Main thing to note is that it can present very non-specifically. So if you've got enough white blood cells, then usually your body is very good at, um, you know, pointing to the source of infection. So you'll cough if you've got a chest infection, or you'll, you know, have an obvious sort of rash if you've got cellulitis or something. Um, but with these patients, because they've not got any neutrophils, often we, we never find the focus of infection. Um, which is difficult. Um, and I think it's in about 50% of patients, we never know what, what the source was. Um, so just be aware for someone who's generally very unwell, has got low neutrophils, be really worried about neutropenic sepsis. Um, obviously examine them very thoroughly and look for the source, so any coughing, urinary symptoms, any pain or swelling around any of their sort of arterial or venous lines, as well.

Um, and then with management, main thing to remember is, um, Tazocin is the antibiotic that is pretty much trust guidelines everywhere. Um, it's also called piperacillin-tazobactam. Um, so, yeah, so that's that's the sort of main thing. Sometimes people also add amikacin, um, but, yeah, yeah, as long as you say Tazocin, that's great. Culture the patient, do your sepsis 6. Um, and then in some patients, we would also give them GCSF, which you might see, um, named as filgrastim, which is basically just a, um, stimulating factor that people get as injections. They're subcutaneous injections, and it causes, or it helps their, um, neutrophil counts recover, um, a little bit quicker than they would otherwise. And obviously, call hematology if you've got a patient, um, with neutropenic sepsis.

Quick note on Myeloma. Main thing to say is you've got your, um, CRAB features, is the sort of mnemonic to remember: so hypercalcemia, renal failure, anemia, and bone lesions. Um, and in your SBAs, if you've got an elderly patient who's come in with hypercalcemia and worsening renal failure, so you know, they'll tell you that their eGFR has decreased or their creatinine has exponentially increased, um, then be very worried about Myeloma. Um, and what is Myeloma? Well, basically, um, it's a, so your, your plasma cells basically clone, and you get a singular plasma cell clone which makes only one type of immunoglobulin. So that could be IgG, um, G, so gamma, or IgG, um, M, D, E, etc. There's several different, um, immunoglobulins that you can make, but you basically just get one of them being produced. So we'll often say things like, oh, this patient's got an IgG Myeloma, or IgA, um, sorry, an IgA Myeloma, or IgG D Myeloma, whatever. So it just means the main sort of immunoglobulin that's being overproduced. Um, but anyway, you get too many of these immunoglobulins, and they can then basically clog up your kidneys and therefore cause kidney failure. Um, and they can also sort of build, crowd out your bone marrow, and if that happens, then again, it reduces the capacity of your bone marrow to produce your, um, your hemoglobin, so you'll get anemia. Um, and then all your other counts can be low as well, your white blood cells and your platelets. Um, and then, so in the image in the bottom left-hand corner, um, it's what I think, so some people call it a "pepper pot skull." There's several different ways of describing it, but essentially that's, um, bony infiltration of the Myeloma plasma clones, across this patient's skull. Um, and also sometimes, as you can see on this red blood cell film, you can get stacks of these, of these stacks of these cells forming, which is also another sort of worrying sign of, um, of Myeloma. Um, and I, there was a rouleaux formation, I was trying to remember what the name of this is, but basically we call, so on that film that you can see, um, it's called a rouleaux formation, where the red blood cells basically stack on top of each other. Um, and then, yeah, I've talked about the, you know, the main features, and then you can probably imagine what kinds of symptoms patients would get. So bone lesions will cause bone pain, lead to pathological fractures, and that's often how patients present. Um, and anemia symptoms, bleeding, infections. Hypercalcemia, that's your, um, there's, there's the other sort of mnemonic, so bones, stones, groans, psychiatric undertones, etc. So just remember your hypocalcemic symptoms too.

Cool. So just a quick note on, um, the hematological malignancies. They're very confusing, a lot of them. Um, but I've just, um, sort of put the key points on here that you should remember for SBAs. They won't really come up in OSCEs. Um, but obviously, the way we split our leukemias is we've got the acute leukemias and we've got the, um, chronic leukemias. So in acute myeloid leukemia, which is AML, the main thing to remember is, um, sometimes in SBA, you might hear the term Auer rods, um, which you, which there's a photo of, and you can see that you just get this little inclusion separate to the nucleus of the, um, white blood cell. And basically, if you hear about Auer rods, you're thinking acute myeloid leukemia. Tends to happen in older patients, whereas acute lymphoblastic leukemia is a disease of childhood. Um, so in AML, or sorry, in an older person, be more worried about AML than ALL. Um, and then in ALL, like I said, it's childhood malignancy. It's got a very good prognosis in children, but much poorer prognosis in adults. Um, and the, the sort of symptoms you get across both are similar. So with both acute myeloid and acute lymphoblastic leukemia, your hemoglobin will be low, so you get anemia. Your white cell count will be, um, well, it can be raised or low, but basically regardless, you've got white cells that are very immature, not working very well, and therefore you tend to get a lot of infections. Um, and then low platelets will often, will result in hemorrhages, petechiae, purpura, etc.

Um, and then so you've got your chronic ones. So chronic myeloid leukemia, um, is associated with the Philadelphia chromosome, um, which is basically, um, associated with this BCR-ABL gene. Again, you may or may not remember from preclinical years, um, but it's good, well, it's not good, but, um, the, the thing is, if you've got this mutation, then we can treat it with a chemotherapy agent called imatinib, um, which is sort of targeted therapy to that chromosome and to that gene mutation. Um, so sort of good and bad, I guess. Um, with chronic myeloid leukemia, you tend to get massive splenomegaly. Remember the, the three M causes: raised white cell count. And then sometimes chronic myeloid leukemia can also progress to, um, become a more acute leukemia, and that often signifies very poor prognosis, unfortunately. Um, and then CLL, so chronic chronic lymphocytic leukemia, very high lymphocyte count. Key sort of buzzword to remember is smear or smudge cells, um, which I may have a photo of, I can't remember, but again, that often comes up in SBAs. So if you see that, think CLL. Um, CLL is way commoner than CML, and usually in elderly patients. Um, and it's often actually just picked up as an asymptomatic lymphocytosis.

So I've just got some questions on here. A few SBAs. I'll just make a poll for this one, and then we'll be done soon. Don't worry. I think that should work. Let me know if not. So, um, so you've got a 56-year-old man here. He's had fatigue, weight loss, hemoglobin's 105, low MCV. Um, his stool has been darker than usual. What is the most likely cause of anemia that we're thinking of? Okay, so, um, so most of you have gone for the correct answer, which is D, which is iron deficiency anemia. So well done. Um, so the main thing that I'm worried about here in this patient who's got red flag symptoms, so he's had weight loss, fatigue, and the fact that he's got a low MCV and dark stool, the main thing I'm worried about here is a GI cause, basically. So either a, um, GI malignancy, so that could be gastric cancer or colon cancer, um, or, um, something like a, you know, chronically bleeding peptic ulcer, which is causing malena, um, and therefore an upper GI bleed. And so in both of those cases, we'd be really worried about it being, um, I mean, in both of those cases, we'd, we'd be worried about it being iron deficiency, um, anemia secondary to a GI malignancy or a gastric ulcer. Um, some of the next most popular answer, the only other answer that people picked was anemia of chronic disease. It's possible, but just remember that in anemia of chronic disease, you'll get, usually it's confusing, but usually you'll have a normal MCV, not a low MCV. Um, and it's very, very rare to get a low MCV. So for the purposes of exams, I would just, I would just learn anemia of chronic disease as a normocytic anemia, not a, um, not a sort of low MCV. Okay, but well done.

Um, so the next question, I'll just make another [Music] poll. So this is a, um, 26-year-old man. He's had an episode of prolonged bleeding after he had a tooth extracted, and he says his dad also had a bleeding disorder. You do his bloods. So hemoglobin is normal, APTT is prolonged, PT is normal. What's the most likely diagnosis? And I'll just give that a couple of minutes for.

Okay, so let's just talk through it. So, um, this is a more difficult question, and I think everyone was more, um, sort of torn about what the answer could be. So, um, 42% of you went with E, Von Willebrand's disease, and then the majority of other people were thinking either hemophilia A or hemophilia B, with a few of you picking C or D. So, um, the answer in this case is E, so Von Willebrand's disease. Um, so in order to understand why it's Von Willebrand's disease, let's just talk about the other options. So in hemophilia A, we basically have, um, insufficient production of factor 8, which would cause a prolonged APTT, you're right. Um, however, with your hemophilia, both hemophilia A and hemophilia B, they tend to present with much bigger and much more serious bleeds. So people tend to get bleeding into the joints, and, you know, just very, very sort of large bleeds from a very young age. Um, and it would be unlikely to present at the age of 26 years. You'd usually have a child coming in as a, you know, new diagnosis of hemophilia. Um, the other thing is, um, both of these diseases, so hemophilia A and hemophilia B, and B, by the way, is a deficiency of factor 9, um, but anyway, with both of these diseases, they are X-linked chromosomal diseases, which would mean that he couldn't really inherit it from his dad, because his dad wouldn't be the one passing on the X chromosome, his, his mom would be. So, so, yeah, so that's why it can't really be hemophilia A or hemophilia B, um, because remember, you get your X chromosome from your mom, and then the dad passes on a Y to make him, to make him, you know, male, basically. So he wouldn't be able to inherit a hemophilia from his father. And the main other reason is, you'd expect much more severe bleeds, whereas when with, um, Von Willebrand's disease, the key thing is that you get, um, mucosal bleeds. So that's much milder things, so things like, uh, nosebleeds, gum bleeds, you know, petechiae, purpura, things like that under the skin, but it's, you know, nowhere near as serious as massive hemorrhages into your joints. So, and yeah, and Von Willebrand's disease is, in terms of its genetics, it's an autosomal dominant disease, so regardless of gender, it will be passed down and can be passed down from father to son. Um, but, yeah, I hope that makes sense. Um, and then someone asked, so it can't be inherited from the father? That's the reason. That's one of the reasons, yeah. Um, but the other reason is also, um, it, hemophilia A and hemophilia B wouldn't present with with such, such mucosal bleeding. They would present with bigger bleeds into the joints, and the classic story would be, oh, you've got a four-year-old child who presents with an inability to walk or mobilize, or is just having, um, is not thriving, basically, and has poor growth, and they've got, and the reason why they can't mobilize is they've got massive bleeds into their joints, typically the sort of knees, rather than mucosal bleeds, um, which are much milder and therefore caused by the milder Von Willebrand's disease.

Okay. Um, so, yeah, and the next question. Oh, this is a bonus question. If the previous man with Von Willebrand's disease developed more significant bleeding, what could you give him to stop the bleeding? Also, I appreciate we didn't spend long speaking about these inherited conditions, just because we don't have time, but I will do my best to explain as much of them as we can. Maybe we can have another talk going into those in more detail. And here's a poll.

Okay, so again, sorry to rush you guys. I'm just worried about time. So, um, let me just look at your responses, but I'll start going through it. So, uh, 41% of you, very mixed responses, but 41% of you picked C, desmopressin, which is the correct answer. Reason being, so desmopressin, um, often used in ED, but also used in hem for patients with Von Willebrand's disease who are having bleeding that, um, isn't stopping. So, you know, if they've got, um, nosebleeds that have now been going on for hours and nothing's helping, reason is that, um, I don't know how, but basically desmopressin stimulates the release of Von Willebrand factor from the stores of Von Willebrand factor in your body. So that would basically cause more of it to be released and therefore help stop the bleeding. There is like a very severe funny type of Von Willebrand's disease where, um, they don't produce Von Willebrand factor at all in the body, and so giving desmopressin wouldn't help because they don't have any stores. But for our purposes, we're just going to assume that this guy has the commonest type of Von Willebrand's disease, which is just caused by, um, which, yeah, in which he does have stores, they're just not released very well. Um, and then factor, some of you picked factor 9. So not really factor 9. Sometimes factor 8 concentrate can help, but we very rarely use it. Platelets wouldn't be, we wouldn't give him platelets because there's not a problem with platelets in Von Willebrand's disease. And then vitamin K is usually used for, um, warfarin, reversal of bleeding. Okay. And GCSF, like I mentioned earlier, is to stimulate the production of neutrophils if you've got someone with neutropenia.

Next question. So, um, in this question, we've got an 8-year-old child brought in by her mom because the mom has noticed this rash that you can see in the photo. There's no past medical history other than a chest infection one week ago. You can see the full blood count there. Everything is normal other than her platelets are very low at seven. What's the most likely cause?

Okay, so quite an even split. The two most common answers that you guys have given so far are B and D, so immune thrombocytopenia and reactive thrombocytosis to infection. You're absolutely right to narrow it down to those two differentials. And I'll talk about why one's correct and the other isn't, but the correct answer here is immune thrombocytopenia. Um, so let's go through the answers. So with acute lymphoblastic leukemia, you would expect all of the other bits of the full blood count to be deranged as well. So, you know, you'd usually expect probably an anemia, so low hemoglobin, and you'd expect the white cell count to be very raised. It might be in the 30s, 40s, 50s, etc. Whereas it's normal here, it's, it's only nine. So that's why it's not ALL. And then, so the correct answer is immune, um, thrombocytopenia. Reason being, this is just a condition that is, um, very common in children and much commoner in children than adults, and tends to have a very clear trigger, um, to to causing it. So in this case, this child had a chest infection just a week ago, and basically what happens is that, um, antibodies are produced which attack the platelets and destroy the platelets, therefore causing this autoimmune reaction. And the main way to diagnose it is that when you have a full blood count, if you have an isolated low platelet count, meaning nothing else is deranged, it's just the platelets, then usually it is, um, immune thrombocytopenia. And that's why you've got the rash in the picture as well. So we've got this, um, sort of pinpoint, um, purpuric rash over whatever part of the body, caused by low platelets, basically causing easy bleeding into the skin.

Now, I just want to talk about D while we're talking about, um, B. So reactive thrombocytosis to infection is very similar to immune thrombocytopenia. However, it's not an autoimmune condition. So your platelets aren't really being destroyed, it's more of a case of it's just a reaction to the infection, really. And in reactive thrombocytosis, you wouldn't expect such a low platelet count. Your platelet counts are more likely to be, you know, like 120, 130, so, or even perhaps at the lower end of normal, so they may be 150, 160, for example. But single digits, very unlikely. Even double digits, very unlikely, to be reactive thrombocytosis. So the main way to tell the difference between them two is how low is the platelet count. Um, so, yeah. And then, um, in DIC, again, a bit like ALL, you'd expect more derangement of your, all of your full blood count, and usually DIC will be triggered by a much more severe infection, so something like sepsis, and you'd have a very ill patient in front of you who's basically bleeding and clotting at the same time. Um, and, yeah, whereas obviously this patient's very unwell, but, um, you know, isn't septic or anything.

Okay, question four. Um, so here we've got a 75-year-old man. He's got type 2 diabetes, hypertension, and heart failure. He comes in fatigued. Hemoglobin's 56. So, uh, he's sent to his local hospital. He gets two units of red blood cells, but halfway through the second unit, he, um, becomes very short of breath. You examine him, he's got crackles, um, to both of his lung bases and a raised JVP as well. What's the most likely diagnosis? This should be a bit more straightforward, hopefully. Almost at the end.

Okay, so, um, so most of you have got the correct answer here, which is, um, A, TACO. And a few of you picked B, so TRALI. And no one picked C, D, or E, which is fantastic. And yeah, A or B are your two main differentials. The reason why it's A is because we've got several risk factors here. So remember I said that with TACO, so transfusion-associated circulatory overload, you've got an overloaded patient, so too much fluid in the body, and he's got a past medical history of heart failure, which is obviously a significant risk factor for that. He may have even come in partially, sort of overloaded, you never know. Um, so, yeah, and then his raised JVP also tells us, um, that he's fluid overloaded. Um, so, so that's the main reason. And, um, if he, with the symptoms, it's with the symptoms, so the shortness of breath, the crackles, it's less difficult to tell the difference between TACO and TRALI, but the main things here are the past medical history of heart failure and the raised JVP. With TRALI, you wouldn't really have a raised JVP. Um, and I didn't give your blood pressure here, but just to reiterate, blood pressure would be normal or low in TRALI, and blood pressure would be raised with TACO.

Okay, good. Question five, I think this is the last question. Um, so 70-year-old woman has a routine blood test. Feels well. You've got her full blood count there, and blood film shows lots of big lymphocytes, which are those purple blobs, and smudge cells, which by the way, if you can see towards the bottom right-hand corner, you've got a, um, lymphocyte with the smudge cells. So, yeah, and what's the most likely diagnosis?

Okay, I'm not going to spend any longer on this because most of you have put the correct answer, which is, um, B, so the correct answer is CLL. And this is literally just something to remember. So just looking at the full blood count, she's got a very raised, um, lymphocyte count. Your lymphocytes, platelets, neutrophils are normal. So, and the other thing is the smudge cells. So if you remember, I said smudge cells, or smear cells as they're often called, um, is basically pathognomonic of chronic lymphocytic leukemia. So that's just something you've got to learn. Um, yeah, so well done on that. I was wrong, this is the last question, I promise. I'm just going to do last poll.

So, um, here we've got a 67-year-old man. He comes in with fatigue and night sweats for the last three months. He also complains that he's feeling very full and very bloated when he eats. You examine him, and he looks very pale. He's got splenomegaly right down to his umbilicus, and also some hepatomegaly as well. What's the most, oh, and sorry, you see a blood film which shows you teardrop cells. What's the most likely diagnosis? And again, I appreciate that we didn't really sort of cover these topics in detail, just because there's so much to cover, but, uh, yeah, try your best.

Okay, um, so again, everyone's a little bit more, more torn in this one, but, um, about 70% of you have gone for D, which is myelofibrosis. And then a few of you have picked, um, a couple of the other answers. Um, so the majority of you are right. The answer is D, myelofibrosis. Reason being, so myelofibrosis is what we call a myeloproliferative disorder, and if you remember, um, these very commonly cause splenomegaly, and he's got huge splenomegaly here. And they tend to present with very, um, vague symptoms. So, you know, the fatigue and the night sweats that you've got here, the, sort of abdominal bloating, loss of appetite, etc. Um, so, yeah, they tend to present very non-specifically. But you could argue that those are also symptoms of some of the other things on here, like, you know, lymphoma, leukemia, which are the other two common answers that you guys picked. However, um, the key thing that gives the, gives away the fact that the answer is myelofibrosis is the blood film here. So teardrop cells are basically again, pathognomonic of myelofibrosis, and it's worth just looking up a picture of these. I'm sorry, I didn't include it here, but, um, you get cells that basically look like tears. And the reason for that is when you've got a lot of fibrosis in your marrow, your marrow is not working very well, it's just full of rubbish, basically, and, you know, fibrous tissue. Um, the cells that are then leaving the marrow have to be squeezed out of this very small space, and so they become squished and look like teardrop cells, um, and sort of, you know, become squashed on one end. So, so, yeah. Um, again, main takeaway point, if you see teardrop cells mentioned anywhere, think myelofibrosis and pick that as your answer.

Um, so, yeah, and that brings us to the end of the talk. We ran over a lot. I'm sorry. I promised an hour, but thank you guys for listening. Um, let me know if you've got any questions. Questions. And please do fill out the feedback form. Um, you do get a certificate for attending, if you fill out the feedback form, which is nice for your CVs too. Um, and, yeah, like I said, just really useful for us to know as well what to improve on, um, in terms of future topics. And just to say that our next talk is this Thursday, and is on Endocrinology. So do come along to that as well, if you're free. And it's, it's advertised on Medall and Facebook as well. But, yeah, thank you. Yeah, it's, it's recorded, don't worry. We will be posting it on, I think YouTube or Medall, so it will be available.