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All right. Hi, guys. My name's that you on one of the co founders of the, uh six PM Siris on, uh, unfortunately, today we're supposed to have hematology oncology, but it was said it's provisional date. Apologize for this. So instead, I'm going to be covering clotting abnormalities and we'll try to recover hematology oncology. Another date. I've just got a little bit of Ah, a sore throat, a bit of a cold, so I might lose my voice at some point, in which case I apologize, but without further ado will get started. So if you haven't done so already, please join our Instagram Facebook and Twitter page. It's how we keep you up to date with the latest Siris on what's happening on sort of day to day updates. We've got the surgical Siris starting pretty soon around the 28th of November, so please look forward to that as well. So even when the medical Siris ends, which is pretty soon in next few days this week we still got another serious coming up less if we immediately afterwards on. 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So we're going to cover him a Stasis and sort of the coagulation cascade, including primary and secondary hemostasis splitting it because that's how we can look at our pathologies. We're going to look a bit of the blood investigations that we do so I in law and activate it partial from the plastic time and what they actually look at and measure and what they mean. We're gonna touch on some bleeding disorders. We're going to touch on some procoagulant conditions. And then the second half of this sort of webinars going to be focusing a bit more on something not very well in medical school or least that wasn't very well to me, which is from about it Microangiography is and maz microangiopathic hemolytic anemia is so let's get started. So a 50 year old gentleman presents to the E. D with bleeding following a soaring injury to his arm coming through the radio artery, the beat has been managed with compression and raising the arm. Bloods were sent for a group and save and for blood count. His platelet count is abnormally low, less than 150. But the cause is not known. What is the first step to him? A Stasis. I'm going to start up nice and simple. You'll get more difficult as we go along. Guys, I'm so surprised you actually have ah mix that of answers. People seem to be split between the vasospasm and deep a look like formation. The correct answer for the first step in particularly primary hemostasis basis. Spasm. So what happens is when you got a bleed from somewhere, the blood vessel sort of reacted a damage by constricting to try and reduce the blood flow, and they go into this sort of spasm in state. Then you have your pain. That plan formacion, which is sort of the initial bit for primary hemostasis following that the platelet plug is is it's a soft cap, so it's not reinforce. It needs to be reinforced with, you know, fiber in mash. It comes from my been urgent, and that's how you form a clot. That's how a plane that plug tends to a clot, which is secondary hemostasis. And then once the areas is sort of clotted, and you stopped the bleeding, it's going to go the clock eventually over time, is going to dissolve, and the area is going to repair itself, sort of appropriately with the clot dissolving itself reduce in size. So those are sort of steps towards hemostasis on as mentioned weird sort of primary hemostasis. So you get the damage blood vessel it exposes sort of the structural integrity in the war particular collagen, Then one willebrand factor binds to these glycoprotein receptors on the sort of sort of college and exposed areas which allows platelets to bind course and play that he's in platelets. Then go on to sort of form this positive feedback loop, where they released sort of two sacks and Granules and alpha granule and sort of a dense granule, which contains lots of different contents, such as from Boxing a two, which will cause further phase of construction. Serotonin again, which also contributes to a D P, which helps with Taylor activation and again sort of activating for managing receptors again, allowing more play. That's a heat and aggregate on. Then, you know, like I said, when the sticky play it's come together and I get that's when you get that sort of plate that plug information. So that's the initial sort of steps of primary hemostasis, so a little bit about secondary hemostasis. So probably the traditional way that they sort of teaching medical schools is that you have an intrinsic, extrinsic pathway that sort of trying to move away from that model of thinking. Although it's easier to think about investigations like iron on a P p C eight of a PPT in terms of the intrinsic and extrinsic pathway. But the way that I'm going to make you familiar with this sort of initiation, amplification and propagation. So what happens is tissue factor gets exposed when you have college and exposure and damage blood vessels. That's why it's called Tissue Factor comes from tissues itself that causes, you know, seven to become fact, this time to come activated Factor seven. That leads sort of this whole sort of cascade where nine becomes activated nine. And then the important step of fact, the 10 becoming activated Factor 10, which is a target of some anti coagulant drugs, and you also need calcium. Calcium's a very important part of the coagulation cascade as well as vitamin K and a few other things. So if if you have a major hemorrhage patient, for example, who is needing, you know, red blood cells, platelets on, do you know other factors or whatever it is? One of the things that you need to consider is making sure that they're topped up on calcium on dot missing on that, because if the yard that's going to sort of make coagulation a lot more difficult. And what happens then is 10 in terms of becoming 10. A gets damp lift fide by despite up by his other set of factors, which include fact nine, as I said, and Factor eight, which is sort of implicated in bone willebrand's disease. And this is positive feedback loop, but from been where, initially, when the first bit of from bone gets made from pro form, been, it's sort, of course, this massive feedback loop where you get amplifying itself, causing more from them to be formed loose lips around, and that helps speed up the formation of a clot. So that's how it difference from entrance intrinsic and extrinsic pathway in that this is saying there's more feedback loops length between each other, particularly this amplification pathway. Where they'll be this from been burst is what they call it that will help speed up with formacion of, ah, sort of strong clot. Instead of just the plain, the plug and from been activated form, it'll eventually turned fibrinogen into fiber in and fiber in is what forms this sort of mesh that overlies the plate in a plug and that traps other red blood cells and platelets and that helps pay the plug become a clot. So that's going to question number two. So a 60 year old lady presents to her GP for her regular eye on our check. She is on more friend for atrial fibrilation, her eye on our target target. An iron is 2.5, so they're aiming between two and free on the measure. The measured I and R is for, But she's well, otherwise. So. Which clotting factors does the in our assess? Okay, it's playing up d. So again we're split in terms of the right sort of. The closest to wants is just about be is just about edged it, which is the correct answer. So in terms of iron, are it assesses fact. 1257 and 10 and occasional wondering were if some of the factors have named all the factors of names, but the ones that you want to know is that oneness, fibrinog and two is profound, been freeze tissue. Factor on for is calcium and and in terms of eye on our so I and I looks at fibrinogen and pro form been so one into 57 and 10, and then the activated partial fumble Plastic time, which is sort of more of a assess. Um, of the other pathway looks at factors 89, 11 and 12. And just in times of profound, been time and iron are so I'm an eye on our is looking a ratio of the patients pro forming time to a normal to normal. Patients perform in time, which is roughly speaking about 11 to 13 seconds. But they standardize into the population of the area, depending on which hospital urine. But that's roughly 11 13 seconds is roughly the normal sort of range for a profound in time. So I and I was just a ratio way of looking at the pro funding time. So question number free. Sorry about that, guys. Question number free. A 25 year old gentleman presents to the e. D following excessive bleeding post dental extraction. He's otherwise normally fit and well, and he states his sister has had a similar issue in the past, which beating this sort of this is patient most likely have Sorry. Apologies, guys. Yeah. Oh, yep. Spicing. The majority of you answered it correctly. So correct Answers one belly bronze disease. So if we're talking about most common sort of bleeding disorders, the most common one, at least in the UK I can't speak for the countries. I just assume it's the same worldwide. It's It's fun Willebrand's disease, followed by that in the UK it's gonna be hemophilia A. And then he may feel, er, uh, sort of be would be the first, most common so in terms of one willebrand disease. So there's a massive spectrum. So even though it's very common as a mass, a spectrum of on Willebrand's disease, where AH lot of patients are asymptomatic weather and most of the time when they sort of present or their issues when there's significant bleeding challenges, see, you know, postpartum hemorrhage, big operations where they're requiring a blood transfusion or massive trauma. That's when you may may sort of first pick this up to this patient's more bleeding a lot more than usual. It's more difficult to stand the bleeding and resolve it, and sort of typical presentations initiates that these patients commonly presented sort of mucocutaneous bleeding's. So that's why, after dental extractions, it could be sort of it can be commonly found off that then epi stacks is so you know, nasal bleeds, and they can just general bruise more easily. Like I said, it's a master spectrum, depending on the severity of disease that they have and most like. People are asymptomatic with it, and they usually only sort of present. Or you find out about it when they have a significant bleeding challenge presented to dinner. So if you're gonna remember which one is the most common, so remember, one better brands is going to be the most common sort of being this order and just very briefly in terms of being disorders. So hemophilia is a deficiency of fact rate. It's x X chromosome length hemophilia be also X chromosome length, and it's related to factor number nine. And with these will see increasing the activated partial from plastic time. With all of them, you'll see increasing the activated partial from last time and with Enbrel, a brands disease which is rated of one willebrand factor, which is closely band of sort of factor. Eight. It's It's an autosomal dominant condition. That's why it's very common as well, but it's also very easily survivable. So that's why it's it's It's the most common bleeding this older because it's such a range of symptoms with that. So question number four, you're 35. You're gentleman presents to eat the following with a red hot, swollen leg. His FEC and COPD Normal's from function marks of Fine Harvey, as opposed to D dimer. He's otherwise normally fit him well. What is the most likely procoagulant disorder that this patient could have? Let's put up the pole. Yep, so the majority of balanced correctly. So the correct answer is back to five lines easily. That's the most comment. Procoagulant disorder on procoagulant disorders I want that are more likely to make you form. Clots, among other things, are much more common compared to bleeding disorder. So that's the one thing to remember is well, but factor five. Leiden, um, on the broke right and disorders is the is the most common condition. So in terms of protein C deficiency, so proteins he's close to it. The protein s and the anti coagulating proteins that are vitamin K dependent will have a little bit more on that later on on with Factor five. Leiden makes a specific is that factor. Five. In terms of activation, it's inhibited by protein C and protein s and what happens when your factor. Five. Leiden. It's resistant to the effects of protein CNS. So regardless of what protein CNS still doing factory line is gonna continue functioning and over function. And because uninhibited you're more likely to form clots. So it's resistance. It effects of protein C and s on, Let's see. So as mentioned, all problem conditions are more common competitive, be eating disorders and when you want to think about pro qua going conditions in particular is young patients presenting with beans from the embolism. So if you have to take a rough age about less than 50 should we say patients presenting with recurrent DVT ease on patient presenting by venous thromboembolism? That's what I mean by VT. So DVT pee that sort of thing, and patients also presenting with VT last on anti coagulation as well. So if a patient comes in with a sort of A B, C is sort of a DVT or PT last on sort of some sort of oral anti quiet, and that's also quite dodgy, unless they've not been compliant. Of course, or if they've got warfarin, that I and our isn't in the measure. But if if if they're following and they're compliant, then that's something else to consider. If that makes sense, procoagulant conditions and, of course, without times have changed with the pandemic. What we're noticing more more often is if someone comes in with a P M e t. Of course, everyone's getting colder tests, but something considered overseas cold with 19 because Covert 19 makes patients very pro correct code caregiver. And we noticed that patients with Kobe are much more higher risk of VT ease some DVTs and peace so they don't to be, especially to have an oxygen requirement that we put on the higher doses of low molecular weight heparin. So that's just another thing to consider if a patient's young and presented with a V T on very cooking terms of our table in terms of bleeding disorders. So as I mentioned, factor five Leiden sort of. It's it's it's resistant effects of protein C, so it's uninhabited and you will continue to form clots, help it forming clots. It's autosomal dominant and decreases your activated partial from work last time, which is what? All of these being the soldiers really do 14 c and s deficiency. So protein CNs as I mentioned, they're anti coagulant proteins. So they stop your coagulation cascade from sort of being over activated. Naturally, if you have a deficiency of these, you're gonna be more like it from clots. So again, another order, some more dominant condition, Auntie from Ben Deficiency. So anti form and free inhibits a multitude of coagulation factors very, very important in a source of the target of some antique wagon and drugs which will cover on the next slide. So inhibits factor to five, 9, 10, 11 and 12. You can see how important this. So if you have a deficiency and this is pretty serious again autosomal dominant and then pro from Bend mutation. So remember, from Venice, factor number two so pro for men is sort of the second last step to forming for advantage for binging and two firemen to form your sort of mesh. So if you have a pro forma mutation that's gonna need to access profound meant, as I mentioned from been burst from the amplification cycle. So you lost lots of profound men. Your natural form or crops. Ultrasound more dominant. So it's easy to remember what happens to the Bloods and what happens to sort of the inheritance pattern. Now people have asked me to cover this good question. I come back to the question after I've done this summer. No worries. So people Prevacid what the target of drugs are sort of said it in a very worthy way. But I think as anything, putting in a diagram is is a lot easier. So you would have heard of NOACs, which are called the new oral anticoagulants, which are really now called because they're not really new. They're called doac, so all that means is direct or anticoagulants. So by direct, they mean they have a specific target that they or specific factor that they act upon. And that sort of know in direct action, so typical examples that you can think about that I have very commonly used in practice. So rivaroxaban apixaban so they have the end with X a b A n. So the weight's remember that they function is they have X ray in the name, which means they act on fact activated factor 10, and that a M in the names for anti antagonist, so day and tightness of fact attend. So when antagonized this factor, as I said, they make you more less likely to form clots and more likely to be so. That's how apixaban on Rivaroxaban work. There's also other ones and oxygen, but I'm looking there will end with the same thing. All work the same way. Then you have other drugs, such as the bigger Try and ends in T r A n tr, meaning from been a end meaning antagonist. So it's a direct from been activated from antagonised, and that's how the big Atran works and then in terms of the heparin's So you've got unfractionated have print and low molecular weight heparin, so I'll start with unfractionated heparin so it inhibits anti from been free. And if you remember, anti forming free inhibits a multitude of coagulation factors. So that's how unfractionated heparin works. Low molecular. It happens very similar in that it forms a complex with anti forming free. But how it differs is that with unfractionated heparin, it also effects factor too indirectly, whilst with low molecular it happened heparin. It doesn't really do that, even though it Excellanti from it. Free. More axon factor 10 A. Like rivaroxaban apixaban All those other drugs do so, although alone like it happened, forms conducted anti for free. It's more. It's more indirectly targeting factor. 10. A. Unlike, say, apixaban, which which indirectly targets factor. 10. A. So that's how unfractionated upper in and know molecular it heparin sort of defer, and you're more likely to get complications from for, actually, heparin such as hate righty heparin induced thrombocytopenia, which will try and come for later on. And that's something else to consider. And sort of the most common things are seeing being used in practice is low Molecular. It happens. The only time I've seen unfractionated happens be used is particularly in vascular surgery, when patients have got sort of from both cysts or a big clock. That's causing the having a skin nick leg. That's the only time I've sort of seen unfractionated Heparin's being used, but I'm sure there is more. Wolf Friend is a coumarin, and I guess so. It what it does it in Hibbitts, a enzyme called Vitamin K, a pox I, which activates vitamin K. Vitamin K, is very important for sort of the coagulation cascade in that there's a number of factors, including to 79 and 10, which are sort of reliant on vitamin K and protein CNS and also reliant on vitamin K. So if you give someone war for that stops them performing vitamin key a pox I enzyme. That means they won't have activated vitamin K, which means to 79 and 10 protein. Uh, we'll talk about CNN today, but to 79 and 10, particularly arm or inhibited. Um, so that means you're more likely to bleed now, the reason why warfarin work so slowly and what we have to do Bridging instead of starting is because vitamin K also acts on protein CNS. And if you remember what I told you, that anti coagulant proteins. So whilst it's sort of also inhibits to 79 and 10, it also inhibits protein CNS. It is a balance between the two that acts on the anti crime on the procoagulant system, and that's why, in terms of a bleeding drug, it's very slow to get the eye and are up and make someone when sort of nonclotting range, because it also acts in directly on protein, CNS So that's why warfarin X slowly. And that's why you need bridging therapy in the initial sort of stages until someone gets to that target iron or whatever that is. So that's why warfarin works like that on. That's a little sort of ones that I wanted to cover. So let's go to the questions because I obviously talk very fast and people will have inevitably missed things on. My voice is also more seducing my voice on. So let's see. Sorry I missed. So was the answer factor. Five line Because, um, yes. So is it more of an epidemiology question sermon and that factor five. Leiden is the most common procoagulant disorder, so it's the most likely one that someone will have. It's much more common than the other ones, such as protein, CNS deficiency, anti from deficiency or, you know, pro forming mutation. And just remember that procoagulant disorders are much more common than bleeding disorders. And among the bleeding disorders from Willebrand's disease is the most common, followed by hemophilia A and then he must really be, at least in the UK Does that make sense? Um, run. Does anybody have any other questions before we move on to the more difficult half of this weapon or promise we'll get more difficult. So, um okay, I'll take that as Ah, I'll take that as a no. For now. Done. Okay, fine. So, uh, let's move on. So, uh, first difficult issue question. Unless you've come to the previous lecture. So a 21 year old gentleman presents to the E D. Which fever, headache and photophobia. He's being treated for presumed meningococcus at the senior part of his binky prophylaxis. He's also receiving doctor Part, which is a form of low molecular it heparin. Three days into his treatment, he's bleeding from both of his cannula sites. His bloods were seen below What is the most likely cause of his abnormal hematology results? And let's pull up the so the majority of your answer correctly. Fantastic. So this is the so many intravascular coagulopathy d i c And let me just go through the blood because I still have men. So we're looking in the blood. The blood film. You can see schizotypal. So what's cases? Sites are red blood cell fragments. So it suggests that there's some sort of mechanical destruction of red blood cells so that's the first sort of clue. The second thing is that the D Dimer rays, which means D dimer, is a product. It's a fire bridge and breakdown product. So when you get five injured from 251 and you have sort of break down release products, you get more D dimer being formed, and that suggests that there's more fibrogen being used up. If that makes sense, enhance your fibrinogen is low. The D dimer is high because your for binging is being used up more for breakdown products in your fibrinogen is low because it's being consumed, which is the clue that I'm gonna mention exits. It's a consumption quite get up. A few that's with the I see is You've got a raised iron are on a raised activated point, partial from a passing time, which just that if we're going to think of it simply in terms of the previous thing that factors within the intrinsic and extrinsic pathways or, you know, all of this of regulation, factors are being used up, and that's what that suggests from both pathways, which means this is a consumption coagulopathy Graduation factors from all pathways are being used up. You've got low from in a gym high d dimer and you've got skittish on your blood film, which suggests that there's a micro and geopathic hemolytic anemia going on, which is a ma. And all that means is that there's an mechanical breakdown of red blood cells which leads to an anemia. And how that presents on the blood film this case of sites, these red blood cell fragments and that 0.1 of these things together a consumption cried a lot a few points towards disseminated intravascular, quite Ganapathy in the context of this patient's condition, which is that he has meningococcus septicemia. Now I'm sure some of you were thinking of heparin induced thrombocytopenia. How it differs. Is that aside, mentioned with heparin news from Ascites, You wouldn't see all of the coagulation factors being affected so you wouldn't see a raised in are raised a PTT all together low for binge eating. All of that together. You wouldn't see that in one package that points more towards the I see. So if everything's being used up consumption quite tomography in the context of something safe, so they're sepsis. But there's other conditions, such as cancers, chronic minor leukemias, other things that points towards disseminated intravascular, quite Ganapathy. And with a d. I see, because you're using up your sort of this is sort of weird sort of paradox in that you're using up your regulation factors and start, you know, forming lots of clots. But your bleeding risk because you're inappropriately forming clots so these clots or fly around and they can eat it from both sides with CP is whatever ski me out and organ damage dependent on where these clots goes because your inappropriate using all of your sort of hemostasis clotting factors and platelets because they were from was like two Penick as well. That leads the bleeding in other areas, such as in this patient already had bleeding from their cannula sites. If that makes sense, so that's how it manifests. So acute. D. I. C. Because there's two types is a chronic and acute. But acutely I see is what you come across obviously acute setting, particularly after seeing you notice from a cytopenia high iron on activated partial from a person time. No for managing because it's used up Heidi Diamond because the fibrillin gyn is being used up and the breakdown trash product of that is, did I'ma and you get red blood cell fragments cases? Sites suggested that there's an MRI going on because all these clots are brushing against the red blood cells and sort of sharing, often destroying them. So that's D I. C acute the I see a least in a nutshell. So it's a clinical on the laboratory diagnosis. As I said, it's It's a process of from boasts and bleeding. And unlike other sort of from bottle microangiopathic, geography is such a hatred such as, you know, all the other ones that we talk about later. They have no more coagulation studies, whilst with the I See, you will not see no more coagulation studies manifested in hiring on High Pretty and I already mentioned of these from by sort of sheer against sort of red blood cells, which is how they cause this sort of microangiopathic immunity can email that's moved backwards. Sorry on. But if you got a spare into acute D i C and chronic the I see. So it acute the icy think sepsis acute intravascular hemolysis trauma patients in particular on acute minor. The chemo has one sort of cancer that stands out on Deekraal. It's typically malignancy, so malignancy I'm using producing, you know, costs normals. I mean things like very in cancers got cancers, lung cancers, pancreatic cancers. That's what I mean. I'm using moose and producing a dental carcinomas and in terms of management, really need to find the underlying cause and provide supportive care. You consider transfusion of blood products, if appropriate. That depends on their sort of HB target and how symptomatic they're always so I e. Have they got low BP posture? Hypertension tachycardia Because of you think because of being under full because of blood loss? If they're fiber engines less than one, then you'd consider giving prior precipitate car precipitate. All that is, it's it's frozen fibrinogen, basically in terms of the PT and a PVT. If they remain elevated, you can give epi frozen fresh plasma, which contains lots of protein in coagulation factors. But really, it's it's to reduce bleeding. So if there's lots of bleeding that something consider giving so it's not normalize the tests and if you've got poor, poor, poor performance, which is sort of this necrosis and bleeding or affecting large majority of the skin. You could also consider giving them protein C now investigations for anybody sort of windy. I see you need an F B C because, of course, you need to look at the platelets. Coagulation studies, because you need to see this consumption going on fiber engine vacation. It's safe. It's consumption going on, democracy increase and again, the blood film to see if that sketch the sites already mentioned the etiology in terms of common stuff. Other things that consider is also obstetric causes such as help syndrome, which includes elevated liver enzymes. Um, no platelets on, As I said, Hemolysis, which is part of it's sort of, um, complications include organ injury, depending on where the four from by sort of go and clot of causing ischemia on. As I said, features include from boasts and bleeding, and I don't think they consider is poor performance, which is very serious complication of it. So moving on, uh, let me move this way. Okay, Sorry. Just a second. Guys shots in the way of the question of in Yet a 27 year old gentleman presents to his GP with fatigue, abdominal pain and the rash over Strunk on examination, the rash appeared to be patikieye, so the number lunch and he states. He was in the hospital recently with in front with in front about disease flare up and I received prophylactic thought upon for 14 days. He's otherwise a fee. Brown has no other symptoms. His full blood count was sent a week earlier. The GP had found some abnormalities, which could be seen the table below. Following hematology advice like a coag Damage fibrogen blood film have also been sent. When is the most likely cause of the abnormal hematology results? Let's bring it on to this question was meant to be a little bit of a trick question in that most of you will split between heparin induced from besides opinion because he's obviously been exposed to some sort of heparin from from the From the Cytopenia. Now the correct answer is, See, it is from about it from a cytopenia proper and hope nobody's picked the I see, not just because it was obviously that in last thing, um, but because there's no consumption going on the on on a PPT are normal, so there isn't a Q D I C. going on, and it wouldn't be hemolytic uremic syndrome because one is there, sort of. It's It's on its way to the presence of the colon, diarrhea and a few other things, but also because there's no kidney injury. So we'll beat up on bit. Wouldn't be helping induced from the side opinion, because it's less likely because of the number of days of exposure you typically see within 5 to 10 days. Follow exposure. That's why I said 14 days specifically, but you have to consider both of them anyway. But the one that you want to consider most likely in a minute is from about it from the site of eating proper. So it's another from optic microangiography like the I see. But it does not consume caregiver a sh. In fact, this has the iron on a pretty normal, and it rarely causes end organ damage s so it doesn't really cause a sort of an organ damage, such as involving the kidneys. It rarely involves the kidneys. Basically, the kidneys are involved. You're less likely to think about from bottle from the site. Penick proper and in terms of blood wise, still get it from the cytopenia obviously, because in the name you have normal coordination studies you have still have. You can have a high deductible or sort of a normal diamond. Because, remember, the timer is also raised in anything that causes inflammation. It's it's Ah, it's a very sort of months, but it's a very sensitive test, but it's very non specific. It's why we use it for, you know, assessing for VT Risk that it could be raised by any sort of inflammation. Eso really the Heidi Diamond doesn't mean much, but he's got a normal fibrinogen, which is the city's not consuming all of it. But again, he's got his blood film. He's got scared sites, which suggest that there's a microangiopathic hemolytic anemia going on. So you probably forming clots and the damage to the walls and inside of the blood vessels for whatever reason, which is sharing off blood vessels so blood red blood cells causing these cases sites to manifest, which can cause an anemia. Now let's talk a little bit about from this side to Penick, uh, from what from besides being prepared. So it's a medical emergency. The thing to remember what it is it's rated Tennis Adams T. 13 enzyme A protease eso. What it does is when you got a deficiency in this in the cities accumulation of these sort of ultra large one winner brand fact. The complexes, which stick the services buying platelets and essentially form clots inappropriately, basically because Auntie thirties help meant to help break up these large complex is that you don't form large, continuous clots, which is why you get from both is from about it on from a cytopenia because your inappropriate using up because these V W F long chains are catching everything within them and because you're forming these microphone buyers. I've said the red blood cell share against them. And this is mechanical breakdown of the red blood cells, which causes cases size on the blood film, which is known as microangiopathic hemolytic anemia when it leads from the anemia because of mechanical destruction of blood cells. So when you think of TTP, think of the Adams tea for thine protease, it can be acquired, which tends to be more sort of dramatic, and you get the formation of the auto antibody or it can also be hereditary, which is a gene mutation of items t 13 and what you want to do is a few things in terms of risk factors. But when you're testing for Adams T 13 in terms activity levels, if it's less than 10% because those ranges of activity that means survey from what from the side of being prepared, it will most likely be the diagnosis in terms of clinical context, on laboratory testing and before you want to test for items devoting activity activity because it's obviously a very expensive test where you want to be doing is this pretest probability scoring, which is called the plasma? Exhorted scoring, which is specifically for acquired from the side Penick for multiple from, besides being prefer, which looks at these factors on day. One of the things that I want to point out is that when you look at the creatinine, it's saying less than 177 because, as I said, there's rarely sort of a k I or acute kidney injury or organ or kidney involvement with TTP. That's why it's less than as one of the things on features again course cases sites from cytopenia. It can cause bleeding because inappropriate use organ involvement could be typically sort of neurological gastro, which we can cause a bomb in pain if you other things and ankle holds, you know, sort of sensory changes, among other sort of funny neurological symptoms. But again, renal vitamin is very rare. Investigations include everything that you do for D I. C. But it also includes hemolysis bloods, which are things like, um, ldh particular sites to see if you're forming new blood cells. You're also obviously check for autoimmune hemolysis. So you be doing it that direct anti body sort of test. And you obviously test Adam's T 13 depending on the plasma scoring and depending on how likely you think it is and the management radius. It's plasma exchange to get rid of those auto antibodies because of the quiet, more common steroids that helps and died on information. And the tax month suppressed immune system is well in terms of those 20 money's starts, the treatment for former cytopenia from not from the side of being paper and the reason why it's less likely to be hyper induced from the cytopenia, although not impossible. It's because of the number of days 5 to 10, but you can still test for hep A and induced from the cytopenia. I hope that covers it. Oh, I think I just answered the question. Biaxin. Okay, broke fight. Let's move on to the next question So and nine, your chart presents. None specifically on. Well, the emergency department, the mother stated here she had seen some blood in her child's year, in theory, was dipped. It was posted for blood and protein. The mother further added, her child in recovery, Cindy from about of bloody diarrhea two days earlier but otherwise otherwise was normally fitting. Well, Bloods can be seen below what is the most likely cause of the hematological abnormalities, and that's about the pool. Sorry, guys. I'm really starting to lose my voice, but we're almost there. There's more. More question after this move straight on because it was given to cancer in the previous one. So majority of answer Karaki it's obviously going to be in genetic. You remix and drums so again, when you look at the bloods I and on a PTT on Normal. But she just and D I C is highly unlikely to be going. One, including the normal for managing the time, is raised because none specific inflammation. They had bloody diarrhea. They've got blood in the urine. It could be from any cause. And what's Qwest is like, which again suggests this mechanical breakdown of red blood cells Lean to an anemia? Um ah ha a microangiopathic hemolytic anemia. And in this case, because they've had bloody diarrhea. And it's a young child and you can see that there's clearly sort of renal involvement in that they've got a positive step stick for blood and protein that suggests that the team elliptic you remix and drunk. So this castle cool on that sort of non classical noneffective hatreds. We're gonna cover the castle, going to guess which is commonly due to. So this sugar toxin producing E. Coli, which is also known a stack hate us. It's more common in younger Children, but not impossible and adults, but it's much we don't really know what the epidemiology in adults is in a can affect adults, but it's just more commonly seen in diagnosed in kids. On as I said, there are courses of hits us other than the coli, none classical sort of hate us, but it's a lot less common. So things can be like sort of a compliment mediated sort of autoimmune type husada that's very different sometimes of Bloods. In terms of steak, it's us again. From the cytopenia. You have normal coagulation studies, usually ah, high or normal D dimer and normal for a bandage it again because no consumption going on like with the I see skin sites again because the May huh very typical renal involvement. Renal Woman's very typical. Where Teen lytic, you're mixing drum again, less likely in from from about it from the side of being proper. Not impossible, but a lot less likely. So if you got renal movement, you go all of the above that someone had diarrhea. You're more like to think of humanistic your neck syndrome on. He's also recent bloody diarrhea, obviously. So, as I mentioned, there is sort of other types of stack, which are less common. Such a compliment mediated Hate us, which I'm not going to cover, and in terms of sort of the time scale of what happens is as you got a nice sort of little timeframe for bloody diarrhea, sort of sugar talks and producing E. Coli related hate us in that we get infected, be coli. On this, you get some diarrhea, abdominal pain, people vomiting that can pretend she progress on the bloody diarrhea and then eating some of these patients sort of off the seventies will improve in terms of the diarrhea and obese complete resolution. Or they can develop the complication of hate us. Now how likely to develop? A. Sure, it depends on sort of what form of equality of got in there if they got SPECI. Coli sugar talks and producing you call it that makes it more like if, depending on which cigarette thing they produce, it's more likely a swell. So the sugar toxin type one and two. So if you produce sugar toxin to to, you know, being more than the more dangerous one, you're more likely to progress on to having hemolytic you remix syndrome. You get this triad of a nonhemolytic anaemia. So we did that. Testing. It's negative. The Coombs testing is some of you guys will know from a cytopenia, and it will typically involve the kidneys so that can manifest in a cage. I know easier far on this sort of less production of urine or, you know protein and blood in your in your in the dipstick? A. Well, um on, as mentioned, typically 5 to 10 days post onset of diarrhea. You have typical hates us some classical eight years, which is sort of stack related, and also she get up. But that's less common, and you're a typical hates us. And as I mentioned, that's a rare causes. But remember, hate us isn't always just caused by a stack. E. Coli and the really carry supportive care. So if they need blood, you can transfuse it. But you don't always commonly do it. The holiday hemoglobin is, or if they're symptomatic with that fluid replacement organs a pro if appropriate. If the kidneys are really failing, make sure the BP slice of controlled. And if they've got sort of CNS and woman or other organ involvement, you consider other sort of monoclonal antibodies such as and can you zoom up? But that's a far as I'm going to go with that because I have you seen a hematologist. So just the last thing that I wanted to mention in terms of HIV, because it's the last one to cover for the from bottle Microangiopathic and Neemia is so in terms of heparin just from a cytopenia and the way that it happens. It's more common with unfractionated heparin than know molecular apperance. But it's not impossible with low molecular heparin's, which is what in that vein. Yet when that person had low molecular weight heparin, it made it less likely, and the fact that it was post 10 days again made it less likely. So that's why the answer and that previous been yet was from about it from a cytopenia proper. But you'd investigate for 11 regardless. So what happens is you get platelets factor for which forms a complex with heparin, which is for you. This is foreign body and sort of what happens is you produces G antibodies to it, which is what causes happen induced from cytopenia. Now, these antibodies that you form that I g specific cause activation of platelets, which is what I got for my information and hand, should get sort of usage of your platelets, and that's why he needs the low platelets. And that's why I can also lead the bleeding. Increase bleeding risk and clot in risk so you get a rapid drop in your plate in the streets. Excessive confirmation typically happens fight to 10 days after, which is again what I've said, and it's more common with unfractionated heparin than it is with low molecular heparin. And again, you get no global sort of consumption. Unlike the icy sermon, if you see global consumption off coagulation factors, manifests and high in our high a p C T on a low did I'm a a low fibrinogen? And Heidi Done that suggests that there's probably acute the I See Goldman. In which case, then, what's the cause of that? And there's sort of two types of hit. So this type one, which is the mild sort of transient drop within the first two days of heparin sort of exposure not very sort of doesn't really cause any sort of connected, significant issues. And dramatic one is the one that you're worried about, which is the one type two when you get those antibodies and then they lead onto a lot. The issues that we've talked about so features include from both says from cytopenia bleeding is less less common with it, But it can happen, and because you're forming clots again, you can have end organ damage because he's from bites, causing a scheme er and blocking of blood vessels. So whatever organ they go to so typically the platelets will be less than 100 50 or it's decreased 50% from the baseline. Platelets A Z mentioned you can get sort of from both sides, which could be venous or arterial. You get injection site necrosis. What you want to do is antibody testing. ELISA, you can also get a constitutional symptoms. But, I mean, they feel generally unwell. Sort of fatigue, malaise, fever, that sort of thing on. That's it. So I'm gonna put the feedback link up and because some of you would want that and then I'll take any questions that you have before I lose my voice. Uh huh. Here we go. Yeah, no problem at all. No problem at all. I think it's one of those things. I just want to specify one more fingers. I never actually said from bottom. Microangiopathic Anemia is so what a TMJ or from bottom microangiopathic anemia is. It's sort of a tissue diagnosis in that when you take a sample of someone's blood vessel when you look at the blood vessel walls that into the internal sort of structure is damaged and there's sort of clots coming off of it. And even though there's no sort of physical trauma or damage on, that's what a TMJ means on. But those tr made conditions that can lead to such as TTP or, you know, hates us is that they lead to those mas so microangiopathic hemolytic anemia like a mechanical physical destruction of red blood cells. Because the brushing against those sort of dodgy, sort of blood vessel walls that have some from my attached to them on because in Canada for sharing, which manifests there's skips the sights on a blood film. So that's what a TMJ means. That that's what, Mommy. And that's how they look at the rest of the questions. Um, okay, I don't think there is other questions. Okay, fine. So in terms of how you access to recording, So cardiology one cardiology, too, And the videos for community one cardiology to have been made available so you can see those ones today the slides and videos, or up for what you want to do is access the videos on the sort of slides. If you haven't completed. The feedback is to go on the Facebook event page for that event. Instance, If you want to go to see the cardiology one stuff, go to Facebook Event page on there on the post, you will see the medal link is there, which is the website with post all of us. You click. It would lead you to the event page where you can access the stuff. But you need to make sure you have a med on account. And for feedback, make sure you could be a matter of account because then you're gonna get a certificate. And when we post the actual content up, it also gives you email to say that we've posted the catch up content up. So that's how the actions recordings and slides. So warfarin on back. So it's like a double edged sword in that acts very slowly. The reason why acts very slowly is two reasons. So remember I said it's related to vitamin K. Vitamin K is sort of I'm gonna write it down because it might make it easier. Let me grab a pen. So, um, from bump a bum. So K is sort of this double edged sword on. I'll tell you why. So the reason is is you know that there's vitamin K dependent clotting factors. And I'll tell you what, those ones up there too, which is profilnine seven, nine and 10. And so, if you have a lack of vitamin K, you're not gonna have activation or enough of these clotting factors, which means you're more likely to bleed. But on that same note, vitamin K, there's also other things are dependent. Vitamin K and that's protein proteins. See on S. And these are part of anti coagulation. Remember how I said they stopped things like Factive five from becoming overactive? Eight hours? So they're anticoagulants, proteins or factors. And these are pro coagulate factor, because obviously you need the clotting factors to form a clock. Now, what warfarin does is remember what I said inhibits that enzyme vitamin K a pox. I'd which I just can't, right. Okay. It looks like I'm just gonna write it. Is that Yeah. Oh, yeah. I'll come back to nuts and minorities. So what warfarin does is it? Inhibits it. Zaventem in case in park side of Haagen. It's the coumarin sort of drug. It inhibits this. When inhibits this, that means you get less vitamin K, which means overall, you can have less of these factors, which leads to the bleeding. But you also have less activation of these factors. But these factors trump these factors, so in that if you inhibit these, these are more like to have a larger of fact, which is why it's used as an anti coagulant medication. And the reason acts slowly is because it also causes in half inhibition of protein CNS, which are anti crackle in factor. So that's from the opposite spectrum of that makes sense. So that's why it takes a while for someone I in our to get to the right level because warfrin acts on both systems. If that makes sense, M. S. And that's why you need bridging therapy until they reach a target. I and R and then once in a target and other they're safe. Does that sort of makes sense a mess. So bridging could be with other things, so it can be friends. It could be it could be heparin injections for a short period. It could be happen injections or, if you prefer not to give warfarin, which is what we're moving away from because a lot easier you'd give you could give the oral anticoagulants instead of warfarin, but dedicates It's Zeppelins that you would use for bridging for a pre know molecular heparin's if that makes sense if you needed to bridge. But you don't always necessarily need to bridge either because, for instance, because you can have warfarin for lots of different conditions. So, for instance, mechanical heart valve is much more important to bridge somebody and get that eye and up to speed whilst compared to a F. If you remember, chads last scoring that what you're worried about, what a F is strokes, which happened over, ah, longer period of time. It's looking at the rest of it in a year. If that makes sense or years, so that's why they have it. It's not necessarily your most important, but it needs to be, you know, closely monitored over the week we multiply and us, which is why GPS can manage it. So it's not necessary. You always the bridging therapy, either. If that makes sense. But if somebody needs to be got needs to be at you quickly, quickly, then you need to do a bridging therapy. And also, if you need to reverse more friends, whatever reason, you can give all the fire pieces well to bridge. And I mean, I hope that sort of makes sense a mess, All right? Never simple as you think it is. Uh, let me try answering the other questions. Now, what is I t p? And how does his presentation differ? So, um, you from Arctic? Sort of sort of the immune immune sort of related. It's do with this sort of organ involvement. And what what complexes you do So I don't know, off the top of my head, but what I'll do, I can't pronounce your name Stories I don't know, slide for I t. P by the end of it because I realized that I haven't covered that. So make sure you add on the slide for I t p A f and I'll make sure that's in the content for tomorrow. When I posted up and somebody asked me How do you please mind summarizing? How do you differentiate between a treaty? Need to be in a vignette There is in my notes and I'm lost again so similar. The way you differentiate it is so firstly, you know, actually have to have heparin. Exposure is the obvious sort of thing. TTP rarely causes sort of renal involvement, but it could be could infect other organs. So it's just the the gut and sort of the neurological. So if that's the renal involvement, TTP is less likely on would hate to I t. Again, what makes it more communist if you give unfractionated heparin and if it's within 5 to 10 days of exposure? If that makes sense, so it's Maurits Mawr. It's more based clinically, but it's also other investigations that you do in that Remember TB, you do your plasma scoring. And if if your plasma scoring is high, pretest probability for TB, you go onto Adams to 13 testing, and if you think it's HIV, you're going to ELISA testing for the GI Antibody complex that we talked about. So that's the other ways to sort of differentiate it, but again it can appear very closely together. So then what can help differentiate? And sometimes if someone's already been exposed to happen, is is doing those further investigations, such of the plasma scoring or going on to do the album. See? Fucking testing or the test for the allies of testing for that complex that we talked about? Does that sort of makes sense? Someone Okay, Um okay. Going, I think that's it. And we finished seven o'clock on the any last minute burning questions, guys. And I had a slight form. I t p you guys can follow that and the so dermatology video and slight and posted up today. And for today's content, it will be post up tomorrow. Make sure to join me. Six o'clock, please. Can you have the meddling for cardiology to please? Yeah, I can do that. If you hold on a shirt, please join me tomorrow where I will be covering end the crime and I'll let you guys know what's happening with gastroenterology Because again, it's one of the provisional dates. It's provisionally dated at the minute, but we still got respiratory one and two and then we've got dermatology to the end. The medical Siris Hopefully and then we move on to the surgical Siris on please complete the feedback and our postop the metal link for the cardiology to stuff you give me a second Yeah. So that's the leg on Here is the page for cardiology to the event page. They gotta for in Berlin. Okay, then, guys, see tomorrow, six. PM Hopefully if my voice recovers because I think it's really started to go now. Take a by, okay.