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Um Welcome to the hematology Talk from Conca Finals. Um This week, the session will be led by myself and Francesca. Um, who's another too? Um, at the same trust as me. Um I'm gonna start um with my section and then I'll hand over to Francesca halfway through. Um We have some questions. It would be great if you guys could just pop your answers in the chat. Guesses are absolutely fine. It doesn't matter if you get the answers right or wrong cos we're gonna go through the explanations. So if you can just engage, try and sort of figure out what you think the answer is, then you can learn from um any mistakes or misconceptions you might have had. Um, if you've got any questions for us, please pop them in the chat and one of us will answer um, when we can. Ok. Um So without further ado, let's get started, we're going to cover not necessarily hematological malignancies, bleeding and clotting disorders and anemia. And we might touch briefly on hematological emergencies, but it won't be the focus of this talk. So that's something you might want to go and read up more on afterwards. So, first question for you guys, I've got a 17 year old um with heavy periods who's always had heavy periods. So is her mum, she recently had a lot of bleeding when she had a tooth removed. Um and she tends to bruise easily but has never had any severe bleeds which of the following might be appropriate for controlling her periods. Anyone got any suggestions, you can also suggest any likely diagnoses if you would like to got lots of you uh in the audience is so anyone brave enough to throw out an answer. We haven't got the, the poles working this week. OK. We've got some d suggestions. Mhm I don't think anyone think other than d OK. We've got an a lovely, anyone got any ideas what this might, what condition this could represent? I mean, there are lots of things that can make you bleed but like with this little picture, what would people's top suspicion be? OK? So the answer I've put here is d we'll talk a little about OK. Someone suggested Von Willebrand disease, which is absolutely what I was going for other conditions as well. But from around is, is sort of your thing to think of when you hear heavy periods bleeding after dental procedures, et cetera. Um It's not usually too severe, although there are different types and actually a a was a bit of a trick because desmopressin is part of the treatment for VRE Brown's disease when you're trying to optimize someone presurgery. But in terms of actually controlling their periods, something like TriC aic acid or the combined oral contraceptive pill would be your more first line treatments. Um, later on you can do something like a hysterectomy, but that wouldn't be appropriate in a 17 year old who's otherwise. Well, um, we'll talk about prednisoLONE, that's for one of the other, um, disorders as, as is riTUXimab that can cause bleeding. And this patient doesn't really need a platelet transfusion. This is um well, we'll talk about Von Willebrand's disease, but it's not a platelet um issue and she doesn't need transfusions all the time. She just needs something to stop the heaviness of the periods. So before we go on to some uh sort of theory, got one more question. So this is a, a girl with this rash on her legs as you see in the picture. Oh, has Francesca made a pole legend? Um Thank you. So she's got this rash I've seen in the picture. One might call it um like petechia or purpura. One also says she's had a, a significant nose bleed this morning. She's otherwise. Well, no temperatures, no other symptoms, no regular meds. We do a full blood count which is normal, but apart from slightly low platelets, what do we think the most likely diagnosis is? Got TTP one will run disease ITP Christmas disease or meningitis. We have a couple of votes for itp. Any other suggestions? Everyone cos I get them all conf I frozen. I know I get them confused all the time. So I put in TTP and ITP and we'll talk about the differences, how you can tell the difference. And then we've got one Von Willebrand disease which can cause bruising. But this, this purpura is more typical in your um thrombocytic cytopenic p et cetera. Christmas disease is actually hemophilia B. Um And then I'll just put in meningitis there just to see if people are actually reading the question. Um You can get a rash like this and meningitis but should be unwell. OK. Six. Oh. Have I pressed the next slide? So I think we've kind of covered some top differentials here for patients that are bleeding. So we've got your form milligram disease, your um hemophilias yours. If we start with Von Bland, I can't use it. Von Willebrand disease. It's a condition where you have a deficiency or a malfunctioning of your Von Willebrand factor, which is a glycoprotein needed for platelet adhesion and aggregation. The problem with the factor is usually due to a genetic defect that's passed on in an autosomal dominant fashion. Um but sometimes it can be acquired due to another um underlying pathology like leukemia. It is the most common inherited cause of abnormal and prolonged bleeding. So, it's sort of one to have in the forefront of your mind when you're faced with a, a patient with heavy periods, et cetera. There are three types as you can see in the top corner. Um So type one, you ha you have some from the road around factor, you just don't have enough. Um type two, you have the, the factor but it, it doesn't function properly. And in type three, you have none at all, which is severe. But luckily it's also the rarest, the most common is type one, which is the mildest. Ok. Um Because of a very, there are many sort of causes in different type. It means there's no single diagnostic test. So you need to take an accurate history. Um and then hematologists will sort of do various laboratory tests. You ask about easy, prolonged or heavy bleeding, including a family history, heavy periods or any known bleeding disorders in the family management wise regularly. They don't need anything so day to day, these patients do not need anything apart from women who are having heavy periods, they might benefit from something like oxamic acid or mefenamic acid, which is a, a similar medication or some sort of hormonal um alternative if they have a significant bleed trauma or they are being planned for surgery. Um I've popped some option on the slide but that will be guided by a hematologist. Um, desmopressin works because it stimulates the release of von Willebrand factor from the endothelial cells. So that only works for type one and two where you have the factor, it doesn't work in type three. If you don't, if you're not producing the factor, then you can't stimulate, um, the release a hysterectomy would only be considered in really severe cases of menorrhagia because it's quite a drastic um, thing to have done moving on to the hemophilias. Um So there's type A and B which is factor eight or nine deficiency. Now, this is excellent recessive. So all males that have even just the one gene will express the disease. But females can either, you know, um have two defective genes or they can be an asymptomatic carrier. So it's much, much more common in males, but it's not impossible in women usually present in sort of early childhood or even in the neonates and can have quite significant consequences. So it's, it's usually more severe than your von will brand disease. Um Things like bleeding into joints can cause joint damage, deformity, et cetera, bleeding into the muscles can cause compartment syndrome. Patients might have, you know, oral mucosal bleeding, nose bleeds, hematuria. But the really severe things are sort of the neonatal, intracranial hemorrhage, cord bleeding, et cetera, um and traumatic um big big bleeds. Um You, you do um assays for the coag coagulation factor to see if there's a deficiency, if you're suspecting it. Um and hematologists might also do some genetic testing, but the management is basically giving them um the clotting factors. So we we can make the clotting factors um give them IV. And that can either be given regular intervals or to a, a big bleed. Ok, over time though, if they keep getting these IV clotting factors, the patient might actually form antibodies against the treatment, which means it's then ineffective. And you really don't have sort of very many options left thrombocytopenia um is means a low platelet count, so less than 100 and 50. Um and that can either be due to reduced production of platelets or increased destruction. So I put a couple of sort of example, conditions that can cause either reduced production or increased destruction. Um We're gonna go over the ITP GTP hit in a second. It's often an incidental finding in an asymptomatic patient, but they might also have easy bruising pronged bleeding, spontaneous bleeding. So you need to be worried about gi bleeds, intracranial hemorrhage, et cetera. Um The reason liver failure causes low is that you get reduced thrombin produced by liver, ok. Um And just like the other bleeding disorders, you can have things like menorrhagia, nosebleeds, et cetera, which is um what our little boy had in the, in the, the question. Ok. Um So last, last, a little bit on um bleeding. I've summarized here the differences between immune thrombocytopenic purpura, thrombotic, thrombocytopenic purpura and heparin induced thrombocytopenia. Ok. Basically, itp it, you can either call it immune or autoimmune or idiopathic or primary. Um And it's where you get these non blanching lesions caused by bleeding under the skin and it's because of antibodies acting against your platelets leading to their destruction. Um, I've sort of summarized how you manage them in different ways but itp, it's, you try and suppress the immune system with, with prednisoLONE. Um, you might need something like riTUXimab or, um, other medications and ultimately, you can do a splenectomy for TTP. You've got, um, uh, sort of a deficiency, um, in the protein DA MT S 13, which normally inactivates from Wi Will Willebrand Factor. Um So where you have deficiency, you get lots of tiny little clots and that uses up your platelets. Um, not only does it cause low platelets and purpura little bits of bleeding, but you can also have tissue ischemia because of all the clots. Ok. These patients might need plasma exchange steroids, riTUXimab, it's much more, the patient's gonna be much more unwell with it. And then heparin induced antibodies um, can be sorry. Heparin induced thrombocytopenia. II. In your question, stem in your, in your, they're going to have had heparin 5 to 10 days previous. Um, and the sort of the main treatment is to stop the heparin and speak to the hematologist. Um, somehow the Heparin induces antibody formation that targets the platelets and it sort of does does, um, are too good a job at stopping clots. So you get thrombosed reading and actually you get abnormal um, blood clots because um, you're sort of causing a, a weird hypercoagulable state. OK. Before I move on to the next set of questions, is any what any questions about bleeding? You can ask questions you think of later as well? Mhm Be here. Why do you guys think? Let's move on to the next question. So this is a 33 presenting to A&E with a swollen tender right cough otherwise, well, has a history of asthma, hyperthyroidism, five previous miscarriages um and is on levothyroxine and salbutamol. She's got no allergies, she doesn't smoke and she has a family history of asthma and blood clots considering this as a DVT. What do we think is the most likely cause? So, we've got a couple of people saying antiphospholipid syndrome. One person saying leukemia, anyone else got any suggestions? Lovely. Ok. So most of you, um, decided it was antiphospholipid syndrome, which it indeed is. So, the clues in this history, um, is an unprovoked DVT in a young person with, um, so sort of a family history of clots and previous mi leukemia can also cause unprovoked or any cancer can also cause unprovoked clots. Um, but she's otherwise well, and that sort of previous miscarriage history or I've spelt I misspelled miscarriage. Anyway, the previous miscarriages in the family history make antiphospholipid syndrome much more likely than, um, like a, a cancer et cetera, other underlying chronic conditions like asthma, they, they can increase your sort of risk but of clots, but probably not the miscarriages. Um, and we'll talk about protein S deficiency and bag Chiari syndrome. Um, as we go through the slides, um, but they are much, uh, protein S deficiency is much rarer and B Chiari syndrome would cause other symptoms. So, your patients had a blood clot. What questions do you want to ask them in their history when you're trying to figure out why sort of what risk factors are there for blood clots? Ok. Disorders. I mean, independent risk factors. So what provoked DVC S? Yeah, immobility. Absolutely. More than three days in bed. So me on holiday. Malignancy. Yeah. So if, if we sort of unprovoked um, clots, we always want to be screening people for malignancy when we're doing our history taking and now examinations, family history, recent pregnancy. Um, so also the combined conceptive pill and H RT, all those sort of hormonal changes. Any more suggestions? Flights a long haul travel being immobile and stuff having had a previous increases, your risk factor again. Ok. I think you guys have got lots of them. So just to make sure we're all on the same page. So a thrombus is a blood clot. An embolus is any type of sort of detached mass traveling through the bloodstream. It doesn't have to be a blood clot can be, um, you know, a fat embolism can be air, it can be other sort of foreign material. And an embolism is when the object, an object causes a blockage in the bloodstream So, if it's a blood clot, we usually call that thromboembolism. Ok. Um Blood clots typically form either secondary to blood stagnation. So for example, when you sat still for ages or hypercoagulate, hypercoagulability or trauma to the um vessels risk factors, we need to ask about in a history taking for real life including things like smoking, immobility and surgery or other trauma to the vessels. Um I had a patient who sort of dropped something on his, on his leg and ended up with a DVT. Um long haul travel pregnancy. I've mentioned all of these things that um increase the viscosity of your blood. So, polycythemia dehydration, autoimmune conditions like sle thrombophilias, which we're gonna talk about in a second, um be suspicious of them when it's a DVT in someone under 40 or they've had a previous one or there's a family history also heart failure. Um If they've had the first venous thromboembolism without a clear pause, review the history examination, et cetera for evidence of cancer. And if you're not going to be giving them sort of long term coagulation, anticoagulation beyond the sort of 3 to 6 months, consider testing them for antiphospholipid syndrome. If they've got family history with first degree affected, also look for hereditary thrombophilias, but you talk to hematology at that point. So, um Antiphospholipid syndrome, the key, the key things to look for in history is recurrent VT E and or recurrent miscarriage. If you think that then you do a blood test to see um if there's any antiphospholipid antibodies. This includes lupus anticoagulant, anti b2 glycoprotein or cardio anticardiolipin antibodies. Um, and if they are present, then repeat the test in 12 weeks time. Um, this is because sometimes in response to infection or medications, we can have a sort of a transient production of antiphospholipid antibodies and that's a harmless um, production of those. So we need to repeat it in 1212 weeks to make sure that we know antiphospholipid syndrome is also known as Hughes Syndrome. So they might use that to confuse you in exams. It's essentially an autoimmune condition. It increases your risk of not just venous clots but also arterial thrombosis. Um And the reason behind it increasing the risk of miscarriage is that mechanism is not fully understood. Unfortunately, um patients that might actually be asymptomatic other than potentially getting a clot. Um or they may be generally unwell with tiredness, numbness, tingling in different parts of the body due to teeny tiny little clots. The treatment is going to be antithrombotic therapy with an anticoagulant like warfarin and potentially um an antiplatelet with like aspirin. But of course, these can cause you to increase your risk of bleeding. So you've got to wear it up for each catastrophic Antiphospholipid syndrome is a rare condition where you get blood clots forming throughout the body, all of a sudden giving you multiple organ failure. It needs emergency treatment in hospital with high dose anticoagulants. So I've put this on here not to freak everyone out. Um But just to, so that I can explain um sort of the next slide. So this is the coagulation cascade where you get all the different factors activating each other. And then on the um right, we have antithrombin inhibiting factor. What does that say? Two A and we've got um protein c um sort of deactivating several steps of the coagulation cascade. Um And it does that along with the help of cofactor, a cofactor called protein S. OK. So they are sort of responsible for down relation cascade and stopping us um plotting too much, which brings me on to the genetic conditions. So, there are several genetic thrombophilias that are worth knowing. Um antithrombin protein C and Cofactor protein s work together to keep the clotting cascade in check. So if we don't have enough of them, um or if they're not working properly, um or sometimes you can get defects in the clotting factors that mean they don't respond to the proteins. Um Then we get a hypercoagulable state. Um and that can cause clotting, but also that risk of miscarriage and other pregnancy complications like preeclampsia, placental abruption, et cetera. And the sort of most common one to know um is Factor V Leiden thrombophilia. Most people will never get a clot with Factor V Leiden. However, one in five people, an unprovoked DVT do have Factor V Leiden So it's, it's a common cause of DVT but the people who have, it may not ever develop a DVT. I don't know if that makes sense. Um So it increases your risk of having a VT before the age of 50 having recurrent VT E having VT during pregnancy or when you start the contraceptive pill or H RT. Um and it can cause clots in weird places that you wouldn't normally get clots like the liver and the brain, but it doesn't cause clotting in the arteries, unlike antiphospholipid syndrome, autosomal dominant. So, family history is very likely. Um and the diagnosis involves doing a blood test to look for activated protein C resistance. Um So in Factor V Leiden, your um Factor V factor five is sort of defective and doesn't respond t. So it can't get become in inactivated. Um So you're looking for that activated protein C resistance in the blood. Um and that will confirm the diagnosis alongside, potentially doing some genetic testing. Um The other ones here are just antithrombin deficiency protein C deficiency and and then a much less common protein S deficiency protein C, if it's um homozygous, it's usually fatal um in the neonate. Um And then the final I think thrombophilia to know about is hyperhomocysteinemia, which just means excess levels of homocysteine in the blood. So, homocysteine is an essential amino acid that we produce it's needed for normal cell cell functioning. But if you have too high levels in the blood. It can cause irritation to the vessels and increase your risk of blood clots. There's lots of raised your levels of homocysteine um including, you know, deficiencies in vitamin B6, um b12 or folate certain genetic deficits. Um So defects, renal failure or m medications that um affect its metabolism. Um So my next slide is about Budd Chiari Syndrome. Does anyone know what the triad of Budd Chiari is or what any of the, the three features of it are? Before I press next. Has anyone heard of B Chiari Syndrome? A clot in the hepatic? I'm very impressed. Um I think you're going to do very well in your final of an angel. Cos I didn't know that when I did mine. Um So it's a thrombosis or a blood clot in the hepatic veins or the inferior vena cava cava cava, whatever you wanna call it that causes obstruction to um the flow of blood out of the liver that's gonna cause hepatomegaly abdominal pain and ascites. So that's the triad of Bak Chiari. It's diagnosed using a, a Doppler ultrasound. Um and it's treated with something to try and get rid of that clot. So, anticoagulants or thrombolysis angioplasty, um A tips procedure which is a transjugular intrahepatic portosystemic shunt where you're basically bypassing the clot. Um or, you know, in severe cases of the liver transplant. Um It, it can happen in many different um conditions, my, my myeloproliferative um and, and blood can other blood cancers? Ok. Okey dokey. So question four. So we've got a 76 year old um with shortness of breath fatigue, bruising lots of infections. He was well before all of this started with only hyperthyroidism in his past medical history. So pretty good for a 76 year old. He does smoke but his lung function tests have come back normal, his bloods come back and show normal thyroid function, but anemia, thrombocytopenia and leukopenia. So the GP arranges an urgent hematology review and the question is, what is the most likely form of leukemia that this gentleman has? So we've got one vote so far. It's anonymous now that Francesca's set up the polls so you can throw any ques answers you want. Does everyone agree with this one response? Ok. There we go. Now we've got some spread. Ok. So we've got a couple of votes for each option. More people are going for CML chronic myeloid leukemia. Okey dokey. So we'll talk about why the answer is what it is um in a second. Um But for this patient, um more likely diagnosis is a ML um but I will go through why that is. Ok. So what conditions are we worried about when we have uh vague here by saying abnormal F BCI mean sort of things like your pancytopenias or unexplained anemias, et cetera. If we think about what I said we'd cover today. Ok. I felt like the question was kind of vague. Ok. Malignancy. Yeah. So specifically, I'm thinking blood malignancies, um, hematological malignancies. So, you've got your leukemias, your myelomas, your, um, lymphoma, also your, my myeloproliferative disorders and your myelodysplastic syndrome. But obviously, we've talked about other things that can change like just your platelets or just this or just that. Um, but in this question, a anemia thro opia and leukopenia. So, well, a pancytopenia and he's got this classical symptoms of each. Um um the shortness of breath, the fatigue is the anemia. The bruising is the thrombocytopenia and the leukopenia is causing a recurrent infection. So you would be highly suspicious for leukemia in this gentleman. So I said my, my or do I say myelodysplastic syndrome, which I will cover on one of my upcoming slides? Don't worry. Ok. So leukemia, you've got an over proliferation of very dodgy white cells. Ok. All the different um blood blood cancers involve an over proliferation of one type of cell to the detriment of others. In this case, it's our white cells are being produced overproduced, but it's not normal white cells. It's weird abnormal ones, which means the um production of all of our normal cells. Our normal white cells is being suppressed. So we get this pancytopenia with the associated symptoms, we might hepatosplenomegaly and allopathy and the systemic symptoms like fever, weight loss and in Children failure to thrive. Um So in the bone marrow, you've got such an over proliferation of what these cancer cells that you've suppressed production of everything else. If you suspect leukemia in an adult, you need to do a full blood count within 48 hours. And if they're, you know, clinically unwell, you might send them straight to hospital. If you suspect it in a child with petite or hepatic megaly, they need to be sent immediately to peds. Ok. Um, although the leukemia doesn't sort of isn't primarily to do with the lymph nodes. Like in lymphoma, you, you might, there might be lymph node involvement as with any cancer it can spread. So that's why you might do a lymph node biopsy. But the diagnostic test is a bone marrow biopsy. All these other ones are just things that sort of paint a bigger picture. Um So like the LD might be raised, the chest X ray might show some changes, bigger imaging can be done for staging. But the the most important one is that bone marrow biopsy um and an LP might be considered if you're worried about C NS involvement. Um Is it changing slides? There we go. Ok. So this is about the subtypes. Um subtypes basically are based on which cell line, whether it's myeloid, myeloid or the lymphoid cell line is affected by a mutation and how quickly it's progressing acute or chronic. These are the main four types. There are sort of rarer other ones as well. Um But these are the, the four to know. Um And they most commonly affect different age groups. Um So I found this on zero to finals. Um This is a little, all cellmates have common ambitions. It's a way to remember the progressive ages that are affected. So A LL is the most common cancer in Children and it commonly affects the under fives, but it can also present in the over 40 fives CLL and CML. You can see on the screen, the ages that it affects and then am L is the most common acute leukemia in adults. So if we go back to our question, um if we can, is it going back there we go. So this is a 76 year old man. So he's in that age group at a ML, he's an adult. So it's just gonna be the most common. He's become unwell. Well, he was previously, well, now he's become unwell. I haven't written how fast but it, it's been relatively fast. Um So that's why it's more likely to be a ML than any of the other ones. Ok. Um Right back here. Um So there are various risk factors for um what we're talking about leukemia. Sorry. Um The different ages, as I've said, Down syndrome can be as um associated with A LL um which is acute lymphoblastic leukemia, autoimmune conditions, ionizing radiation smoking as well. And we'll talk about myeloproliferative disorders in a second, but they can transform into acute myeloid leukemia just to make sure we're all on the same page. The acronym stand for acute lymphoblastic leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and acute myeloid leukemia. Ok. So management, as we've said, you do as an F PC and he referral if they are well in front of you, you need to do an at approach and then an oncology MDT will lead management which will include most likely um some sort of chemotherapy steroid therapy. Um and depending on, you know, which organs are affected, potentially radiotherapy, bone marrow transplants, surgery, et cetera. So this is just a little overview of the cell lines. So it's very simplified. There's way more stats. We basically have the myeloid side which gives you your red blood cells, your platelets, um and your sort of neutrophils, eosinophils, your fills. Um And then you've got your lymphoid side which gives you all your different types of lymphocytes. Ok. Oh, actually going back apologies. Um So um the ones that have um blast in their name um give you these blast cells. So in I've lost, I've lost my side. Apologies, everyone. Ok. So in the acute leukemias, you've got lots of immature cell turnover, very fast um turnover in the acute leukemia as that is. Um So you're going to have these big large immature cells as you can see. And if you look on the, the diagram, the myeloblasts and the lymphoblasts, they have these big undifferentiated nuclei. And then as it goes down, it becomes more differentiated. And then if you look over on the left at the picture on the right, sorry. At the pictures of the histology, you've got these big purple abnormal cells. The bottom one has a little sort of little stem sticking out of it. If you guys can see that now, that's called an hour rod or an hour back body, which is a crystalline cytoplasmic body that can sometimes be seen in your myeloblasts in acute myeloid leukemia. Ok. Um But if that's absent, it could, it's still a blast cell and you, the high levels still are suggestive of a, a leukemia and acute leukemia. And then in chronic lymphocytic leukemia, you've got the office set of lots of immature cells, you've got quite old fragile cells and these fragile white blood cells they rupture and you're preparing the blood film cos you're sort of spreading the blood across the film and you're gonna damage some of them leaving a smudge on the film. So if you can see it kind of looks like, looks like a little um like a squid or something, it's been sort of squished and that's called a smar cell or a smudge cell. So those are key things to listen out for in your um like MC QS. So blast cells, our rods um and smudge or smear cells. I'm just gonna put in the um how do you spell our roads? Ok. Ok. So moving on to lymphoma. So, lymphoma, um now you've got of the lymphocytes in the lymph nodes, which is gonna give you um sort of enlarged lymph nodes, usually non tender, firm and rubbery. It's gonna give you some bee symptoms. Can anyone name the bee symptoms? For me, there are three that I'm interested in and also some nonspecific symptoms. Um, if anyone can think of the bee symptoms, pop them in, but I will carry on for now. Um There were loads of different types of lymphoma. Um and someone came along and called one of the types hodgkins and then all of the other types are called non hodgkin's. Um But they actually present pretty similarly. Um and they use the same classification system but they have very different sort of natural histories and some of them are really aggressive. Some of them are slow growing and the cells are gonna look different under a microscope, but the patient might feel the same. Anyone got any of the B symptoms, you might get a lymphoma, weight loss, fever, night sweats. Thank you so much. Great job. Ok. So those are the sort of official B symptoms. You might also get other sort of nonspecific symptoms like fatigue, itching, cough, shortness of breath, abdo pain, recurrent infection, but they aren't official B symptoms. So, in the classification, um you get sort of a little A if you've got no B symptoms or you get a little B if you've got these symptoms. Does anyone know what the um classification system is called? I've, I blanked it out there. Does anyone have a name for it? Deviation is based on your sort of your imaging? Um And it's about how many nodes are involved, how many sides of like, is it a about just above the diaphragm or just below, or is it both sides of the diaphragm that there are no um lymph nodes involved or is it widespread everywhere and also non lymph organs? So, I've got a suggestion of Ann Arbor. We'll just go to the next slide. So. Oh, no, it's not working. Ah Lugano. Ok. Yeah. There we are. So it used to be the Ann Arbor but it's now been replaced by the Lugano classification, which is used for both Hodgkins and non hodgkins. And then I've just popped down there about the A or BB symptoms present. Ok. Um, so, um, in terms of investigations, your diagnosis is gonna be on based on the lymph node biopsy and looking at this individual cells, unlike, looking at myeloma, you don't typically get a pancytopenia in lymphoma, but you, you can, but it's not sort of one of the presenting features. So how do we know if it's Hodgkin's or not? It will have reed Sternberg cells if it's Hodgkin's lymphoma, um, which is these abnormally large cancerous b lymphocytes where there are two nuclei and prominent nucleoli. Some people say it looks like an owl with two large eyes. I will let you guys decide if you think that's the case. It's a treatment. It varies depending if it's on the type. But Hodgkins is usually quite aggressively treated with curative intent, um with chemotherapy and, or um a and possibly radiotherapy as well. It's usually quite successful, um because it's quite an aggressive um, cancer. So, um, treatments to stop um growth and, and kill the cells is quite effective, but there's a high risk gaps and there's quite a lot of side effects as well. So chemo can cause increased risk of infection, cognitive impairment, secondary cancers like leukemia, which is quite unfair and fertility problems, et cetera. Of course, radiotherapy also increases your risk of a second cancer, especially like if it's on the chest infertility, local tissue fibrosis, et cetera. Um And then non hodgkin's really depends on the type of, of lymphoma and on the stage. So some of them, the really slow growing ones that aren't causing symptoms can be a watchful wait approach. Some of them might need chemotherapy, monoclonal antibody stem cell transplants, et cetera or, or radiotherapy. Um I don't think for your finals, you need to know the, you know, which chemotherapy regimens you use for each. I think that's a little bit too specialized. Um So you've confirmed a lymphoma on your biopsy and you wanna do some treatment but you probably need to do um some investigations first. Um to see are they going to do well enough, et cetera. Has anyone got any suggestions for baseline tests we need to do before we start any treatments? Um Once we've confirmed it, some phone, before we start treatment. Is there nothing anyone would like to do? Yes. So we've got full blood count using these uric acid. Lovely. Ok. So there's several things we need to do. We definitely want to do when um use knees and also LFT S because that can um the treatments can cause kidney and liver damage. We've got some more suggestions here. Chest X ray. Um probably, yeah, I've probably done some imaging already HIV, test generalized immunocompromised stuff. Absolutely. So, a viral screen is really important because chemotherapy can reactivate your latent viruses and some viruses actually are associated with certain lymphomas. So they might have had the virus virus that caused the lymphoma or they might have something latent that the chemo is going to reactivate. So it's really important we check for any kind of um underlying viruses like HIV, you may want to do a staging scan. So it ideally a, a pet CT. Um but if we're in a rush for treatment, then we can just rely on a CT LDH allows us to do risk stratification. So it doesn't, it doesn't, it doesn't tell us whether or not they've got lymphoma. But once we know they have lymphoma, it can help us um stratify risks. Um we want to replace the Vitamin D if it's low, we want to test the HBA1C if we're planning on giving them steroids. Um And we're also gonna want to do an echo prior to starting treatment if they are over 65 or they have any cardiac um comorbidities. Um because the, the treatments um can be sort of cardiotoxic. Um I think the uric acid, um someone that someone's mentioned um is because basically when you give aggressive treatments for cancer, you can get um sort of release of the cell contents. So sometimes we have to give allopurinol. Um So if we can get that prophylactically alongside our chemotherapy treatments to mop up products. So, Hodgkins versus non Hodgkins, Hodgkins is has this bimodal distribution and is good, aggressive but treat, but it also makes it treatable. So that can be quite good. It has a really high cure rate. Um And um like we've said it has the reed stg cells, it's associated with several viruses and also autoimmune conditions and it can seem to run in families. Non hodgkin's can be broken into high grade aggressive tumors and low grade less aggressive tumors that are actually quite so slow growing that they are harder to treat. Um There are lots and lots of types. It's a very broad category, but I've popped some on the screen that I think are important to be aware of. Um, diffuse large B cell is the most common type of high grade non Hodgkin's. Um and then Burkitts is, is the most aggressive and it's associated with viral illnesses. Mantle cell is the least treatable. Um And then I've popped um some slower growing ones there. So general risk factors for non hodgkin's lymphoma include HIV H Chlori which is associated with multi lymphomas. I haven't popped them on screen. Hepatitis B and C pesticide exposure, trichloroethylene exposure. Um I'm not sure where you would be exposed to that. Um And also family history, like with hodgkin's. Ok. So stem cell transplants are an option for um different types of cancers. There's allogenic where you get the stem cells from someone else and that's to replace your um cells. And that can help treat something like a leukemia because it produces a new immune system that recognizes your cancer cells and sort of um means you target your own um cells and helps you clear them alongside the chemotherapy. That's great. But it also can reco that new immune system that you've created is also gonna recognize other cells when your body is foreign. Uh It's gonna cause things like liver failure, et cetera. So patients need to be on this for at least three months after having an allogenic stem cell transplant. Autogenic has less of that risk. It's your own stem cells that you sort of give back to yourself. They're frozen before you have treatments and then replaced to rescue your cell count. Um So that's for treatments where you're going to, to sort of destroy your bone marrow. Um but the actual bone marrow is it was healthy before. So you wanna basically put it back. OK. We are nearly done with blood cancers. I promise I will hand over um to France Jessica shortly. Um So multiple myeloma are covered in the renal talk. I'm not gonna go over it in too much detail. Um But you've basically got an over proliferation of the plasma cells which are the um cells that produce antibodies. Um The abnormal sort of antibody can either be a whole antibody or a sort of just one of the light chains. Um and they come marrow stopping the production of other cells just like in leukemia and you get pancytopenia and then these abnormal paraproteins, they can cause damage in the kidneys, reducing your renal function. They activate osteoclasts causing breakdown of bone, which can cause your osteolytic lesions and your hypercalcemia. And that's what gives you your crab um features over there. On the right. You can do your initial bloods which are gonna show pancytopenia, high calcium raised, you know viscosity and E sr you're gonna look, do look for sort of abnormal proteins in the blood and the urine and then confirm your diagnosis with a bone marrow biopsy as well as imaging for bone lesions. So, um ideally you do a whole body MRI but a CT or a skeletal survey is also acceptable if you've done a chest xray, you might see a lot of sort of these punched out lytic lesions. And if you do skull X ray, you can get what's called a pepper pot or ranger where you've got lots of lytic lesions. Um Common sites of the myeloma bone disease is the, is the skull and the spine. Um and also like long bones in your ribs, which you might might see on the chest X ray, you get these sort of abnormal areas of, of bone metabolism leads to sort of thin fragile bone, you know, that fractures easily. So pa pathological fractures. So you can get, you know, a vertebral body collapse or really easily break your leg with low impact trauma. You can have um what's known as M MGUS or G US monoclonal gammopathy of undetermined significance using a specific power protein, but it, it is not causing any features of myeloma. There's no symptoms. So that might have been an incidental finding and it just basically, just needing the hematologist usually ring them up once a year and go any symptoms. No great. It's been a year. Um just because there's a small risk of progressing to myeloma. But at that moment in time, they do not have myeloma, then there's also something very similar called smoldering myeloma. Where not only are you, you have the paraproteins, but you have some abnormal plasma cells, but again, you have no symptoms. Um and about 10% of these will turn into myeloma treatment. Um is gonna involve um chemotherapy, potentially stem cell transplants. Um, radiotherapy can help with bone pain, bisphosphonates can suppress your osteoclasts. Um And in in cases of a fracture or you know, spinal compression stuff, you might need orthopedic surgery. Ok. So, lost these lines and then we hand over to Francesca. So, ok. Um Non means we call them hematological um malignancies. So these are less likely to come up in finals, but I would read up more about um the next two slides somewhere like zero to finals has a really nice summary of what is useful to know. So I don't have time to go into a lot of detail. Now, my myeloproliferative disorders um is basically where you have uncontrolled proliferation of a single type of stem cell, but it's a much, much slower progression than one of the other um types of cancer. So, it is technically a cancer but very slow progression. The main risk here is is risk of transformation to aml acute myeloid leukemia. So that's why these patients need um monitoring um and probably um replacement of anything that's missing in the body. But like I say, re read up on this a little bit more on your own time. Some examples is primary myofibrosis where you have the Hema hematopoietic stem cells, um perforating out of control polycythemia vera where you have your erythroid cells um multiplying lots. So you end up with a high hemoglobin and your essential thrombocytopenia. Do I mean thrombocytopenia because you've got high plate thrombocytosis. Essential thrombocytosis is where you've got overproduction of your megakaryocytes and you end up with high platelets and there's no other clear cause. Ok. And then finally, myelodysplastic syndrome, which is the one that I mentioned earlier and someone asked about. So this is a cancer where a mutation in the myeloid cells. So if you remember, I showed you the different branches of the, the production of the cells results in inadequate production of your blood cells. So, innovative hematopoesis, there are several different types, but essentially it's gonna cause a pancytopenia and just like myeloproliferative disorders. There is a risk of transformation into A L. These patients can just be sort of watched and monitored closely. They might need replacement of the different blood components. Um And the hematologist might consider something like EP O to stimulate um red blood cell production or G CSF to stimulate neutrophil production. Chemotherapy and stem cell transplants are also options. But often these patients will just have a watch and wait approach. So any questions on my section before I hand over to Francesca? OK. I'm going to stop presenting and we'll hand over you. You muted. OK. Can you see my screen? OK. Yeah. Yeah. OK. Cool. So um are we talking about anemia and hematinic deficiencies? Um I know sort of we pressed for time. I think this is the end at half a test or do we have longer um ha half eight or or later is fine? Ok. Sure. Um Well, we're gonna give the slides to you anyway. Um but yeah, let's get started. So firstly, just talking about the components of blood. So this is just a quick overview. So 55% is plasma and then the rest are the platelets, the white cells and the red cells. So we're gonna be foc focusing on and so the red cells. So anemia is reduction in hemoglobin or red cell count or the hematocrit and the hematocrit is the percentage of the red blood cells in the total blood volume. So on the right, you can see the table of the different sort of cut off. So for men, it's about 130 women, slightly less and Children is around sort of 110 and same with pregnant women as well. So in terms of red cells, um they're made continuously, they last about 100 and 20 days and tests sort of show briefly about the different sort of lineages of the cells type. So I won't go into that. Um But this is just sort of what a normal blood film looks like and what the normal appearance of a red cell is. So we'll just start off with a little quiz. Um If anyone could put down that answer of which of these do not cause microcytic anemia. Does anyone have any idea? Ok. So we have a few es. Um let's see. So the answer is um anemia of chronic disease. Um anemia, chronic disease is usually normocytic and this is the next slide. Um So this is just a brief overview. So it's quite good to classify anemia according to the M CV, see the mean corpuscular volume, which is normally around 80 to 100. So, microcytic is most commonly iron deficiency, but you can think about sort of thalassemias. Um anemia, chronic disease can be microcytic, but it's normally normocytic. Um and in the patients with acute blood loss, you can get normocytic anemia as well. And then macrocytic, you can think about some of the more sort of rarer sort of wonderful diseases like hemolytic anemias, melas anemia. Um and patients who have a history of alcohol misuse or liver disease, that's usually macrocytic as well. Um You can also split up anemia in terms of the causes, whether it's more congenital or acquired. So acquired, we can think about sort of dietary deficiencies such as an iron b12 or folate. You can think about any pathology in the bone marrow, um including leukemias and cancers and chronic disease as well. And then congenital is a lot rarer, but we can think about any sort of membrane defects causing changes in the shape of the red cells, like hereditary spherocytosis or a defect in the hemoglobin chain itself, like sickle cell or thalassemia. And then some of the rarer sort of enzyme defects as well. So we'll briefly talk about iron deficiency anemia, which is the most common type of anemia, especially, you know, when you start working as a junior doctor, you'll come across this sort of all the time. Really. Um, so does anyone, can anyone give me some ideas of any symptoms or signs of iron deficiency? I can give a few because we're running out of time so often, you know, when you do the clinical examination and like a oy, you'd look at the nails, look for any sort of Coron, um look around the mouth, any sort of anglo dermatitis. Um in Children, you can get a which is kind of a rare sort of disordered eating in Children that um where they sort of eat things that aren't really normally eaten, um such as like paint and soil. So it's kind of a rare sort of symptom, but it can happen. Um And often, um when you, when you become a junior doctor, you can see a lot of people presenting with um shortness of breath, palpitations and fatigue and that they can be nonspecific signs suggesting anemia as well. And when you listen to the chest, you can also hear a flow murmur at times. So in terms of causes of iron deficiency, um it's the most common cause of anemia worldwide, often due to poor intake. Um, so diet um for absorption, if you're thinking about sort of autoimmune diseases, including Celiac and Crohn's and in pregnancy there is an increased requirement. So, um a lot of pregnant woman can become anemic as well. And in older patients, um you want to make think about sort of bleeding, um often sort of gi malignancies, which is why, you know, fit tests are commonly done in patients of, of um 65 and above. And you want to think about, you know, um cancer IBD. Um So yeah, that's a really important thing to sort of rule out. So, in terms of the diagnosis of iron deficiency, obviously, you want to do a for a history and examination request a full blood count and your iron studies. And this table sort of explains about um how you can sort of differentiate between iron deficiency and anemia of chronic disease. So, um serum iron is low for both of them. Um and transferring situation is low both, but transferrin itself is high in iron deficiency because um it's a carrier protein for the iron. So when there's sort of a lack of iron, there's a lot of transferrin carrier protein sort of hanging around in the circulation. So that's why that can be high. And so when you're looking at um iron studies, you'll have sort of low MC VMC H and hemoglobin will obviously be low as well. And in terms of ferritin, um it's an acute phase protein. So it's involved in iron storage. So that's low iron deficiency but can be normal in chronic disease. So management, as you can see from the pictures, um I think the most important thing is finding the underlying cause. So if you're query, sort of bleeding and if it test is positive, then you need to do a OGD or colonoscopy. And in terms of treatment, you want to advocate a diet rich in iron. So sort of lots of leafy greens, um legumes, for example. Um and you know, iron tablets are very common, but they have very nasty side effects and people often can't tolerate it and it's quite constipating. So especially in elderly people, when you find a IDA, um IV iron is actually very good. It can be just given sort of one dose and then um it's better than sort of taking tablets every day and patients then become severely constipated. Um So that's a really good sort of option for elderly patients moving on to folate deficiency. So this can often be due to low intake and again, sort of malabsorption sort of disorders and some drugs as well. And again, in pregnancy, they need increased requirements. So as I'm sure you're aware of pregnant women are advised to take folic acid and um other drugs can cause increased excretion of folate as well. So in terms of the symptoms and signs it can be the one seen in anemia, but you can also get uh bursitis. Um you can get neurotube defects obviously in Children, which is why um pregnant women often have to take folic acid supplements. Um and it can lead to hyperpigmentation of the skin as well. Um So just another question, does anyone know what symptoms are commonly associated with B12 deficiency? Well, I think if you think about sort of like a neurological examinations, um often b12 deficiency can lead to uh neurological signs such as paresthesia, um muscle weakness, difficulty walking and peripheral neuropathy, which I'm sure you're quite aware of. That's a very common cause being um b12 deficiency. So, in terms of um folate replacement, it's always oral. Um and again, um for pregnancy, you can give 400 mcg or 5 mg if there's certain risk factors as well and moving on to B12 deficiency. So, that can be seen with poor oral intake, um malabsorption disorders or even some drugs like Metformin and it can become genital. So if you're thinking about um sort of those um pernicious anemia type. So, um meaning that there's malabsorption and you can get some apparent deficiencies with oral contraceptive pill as well. Um because they can influence the binding of B12. So it can cause some like an artificial decrease in the B12 as well. If you look um at blood tests and pernicious anemia is the disruption of intrinsic factor in the gut. So that can cause impaired absorption. So B12 replacement, it can be given orally but um im is quite good um route as well. Um But it is very important. Again, as for all of them to just find the root cause. So, moving on to hemolytic anemia. So, hemolytic anemia is when red cells are destroyed prematurely. So that could be intravascular within the circulation or extravascular in often the spleen um and extravascular is a lot more common. So what when this happens? Um there's decreased oxygen carrying capacity in the blood um leading to hypoxia. So this means that more ep os ex secreted, leading to more red cell production and increased reticulocyte count. So, in terms of a screen, you wanna do a full blood count, um a blood film, um LDH which is measure of cell turnover, so that LDH is often raised and you need to look at heptoglobin and unconjugated bilirubin. And ad test can be used to see um whether there's an immune cause to the hemolysis that's going on. So we'll talk about the intravascular causes. So, um there are a lot of causes. So I'll just give you sort of a brief summary. So if there's activation of complement inside the blood vessels, it can lead to lysis of the cells. So for example, if there's um a bo incompatibility and autoimmune hemolytic anemia, um if there's direct destruction of the red cells, um for example, due to toxins, trauma or infection that can lead to hemolysis and there are sort of these thrombotic states. So D IC um TTP hemolytic remix syndrome. So, what this happens is um the blood vessels, they have these abnormalities which lead to sort of sharing of the red cells. And that can cause the red cells to hemolyze. And then you have some sort of deficiencies like G six PD and Pyruvic kinase, which can lead to hemolysis within the blood vessels and then moving on to extravascular. So this is when the red cells in the spleen are sort of phagocytose and this can occur if there's sort of antibody binding to the red cells. For example, if you're thinking of hemolytic disease of newborn, um and autoimmune humanity anemia as well. Again, infections toxins, any defects in the red cell structure that could cause destruction in the spleen. And if there's splenomegaly due to secondary causes like CML or cirrhosis that can cause hemolysis. So this is just a very sort of a summary of, you know, hemolytic anemia. It it covers lots of different causes. Uh I found this really useful sort of flow chart from Gee kinetics and I can always put a link on later and to help sort of differentiate because there's immune and non immune causes as well. Uh We'll briefly talk about sickle cell anemia. So this occurs um when there's sickling of the red cells because there's a normal beta globin chain in the hemoglobin. So this causes the red cells to polymerize when there's a lack of oxygen. So this distorts the cell into a sickle shape. Um and there are lots of different types of sickle cell. Um and it depends on sort of genetics. Um, so hemoglobin S gene from one parent and for example, hemoglobin c from another parent. So there's HBSS, which is the most severe HBs C or HB S thalassemia. So if you, if a parent has a sickle cell trait, so one abnormal hemoglobin um abnormality, then there's a 50% chance of passing the gene on. And so, um sickle cell screening is often offered to nearly all pregnant women, especially those with high risk factors. And in terms of sickle cell crisis, this often occurs firstly, in these sort of younger Children where they can get sudden onset of pain and acute crises when the, so since you get stuck in the blood vessels and that can lead to infection and of course anemia. So does anyone can give a guess about treatments for avoiding these crises and managing sickle cell? This is probably the easiest question in the um presentation. Yeah. So you got e essentially, so all of the above already. So just avoiding dehydration, keeping well hydrated and also avoiding um the cold. Um alcohol is dehydration and smoking. There's some links that it can cause a crisis as well. Um So if any of you one day have particularly like a pediatric placement, you can, you often find patients coming in with their first or second sickle cell crises and it's really important to ensure you give um IV fluids, um strong um sort of opioid analgesia, like morphine and making sure that they're regularly on penicillin and folic acid to help prevent these crises. Um So, like I said before, you know, it's really important to manage these crises because it can, it could even cause a stroke. So, um and acute chest syndrome, if there's sort of blockage um in the lungs, so you would need to treat that with oxygen as well. And these patients are often severely anemic. So they might need to have regular blood transfusions and hydroxycarbamide, which is a once daily medication, um increases um hb um the fetal um version of HB. And so this helps to reduce the proportion of the sickle hemoglobin in the blood. Um So that's a really useful medication as well. And this, there's these allogenic bone marrow transplants which are quite rare, but that can be an option in more sort of exceptional cases where um healthy blood or bone marrow stem cells from a donor are given to the patient. Um And then lastly, we're just gonna briefly about sort of thalassemia. So you have alpha and beta and, and you know, there are different phenotypes depending on sort of how many um basically on the in inheritance pattern. Obviously, if you have both, um if you're homozygous for the major form that's going to be more severe. Um And features of hemolysis are present and you can get splenomegaly and the management is usually having blood transfusions every 3 to 5 weeks. Um and you can have iron therapy as well where you remove um excess iron from the body as well. Um But it's really important that you support these patients, make sure that they have um you know, enough Vitamin C and iron in the diet as well and they can be suitable for sort of bone marrow or stem cell transplants in the future as well. So, um that's just a very brief overview of sort of anemia, sort of iron deficiency, um folate B12 and then briefly on the hemolytic anemias. Um Does anyone have any questions for now?