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okay, Print. So here's what we're going to be covering today because, uh, clotting abnormalities is such a can be such a broad subject broadening you think it is. To be honest, it can be a bit more complex. He think it is, but we'll break some of the basic concepts down, will go back into basic physiology and cumbersome some of the interesting stuff. So I'm gonna go back diving into HEMOSTASIS primary secondary, and what it will encompass is because this is where it all starts with the clotting abnormalities. We're going to go through what I and R and activated partial from the past in time is we're going to touch on some pleading disorders. They probably would have really come across. We're going to touch on some procoagulant disorders, and then we're gonna go into a bit more detail of the things that I think are more interesting but not covered. Very well, come up. Lots of exams were not covered very well in medical school is the from Bottle Microangiography is and will explain about what that is a little bit later on. So, first question, we're going to start off nice and simple, so 50 or gentle and present CED with bleeding following sawing injury to his arm, cutting food or radio artery. The blood has been managing a compression of raising the arm. Blood was sent for a group and save enough before blood camp. His platelet count is abnormally low less than 1 50 but the cause is not known. What is the first step to the Ms Stasis? And that's part of the pool. Yeah, I agree. Uh huh, Interesting. Stuck between 50 50 actually. Fine. That's under Paul. Her shoulder results so exactly neck or neck mean it's the first time I've ever seen. That s so the ones that are all right are beasts of bees. The correct sort of first step to hemostasis is bass Oh, spasm. So that's talk a little bit about hemostasis and specifically primary hemostasis. So when you get injury or bleeding, the blood vessels will vasospasm and constructive reduce the blood flow to that area and I'll keep spasming on. Then what you'll get is following that. You'll get primary hemostasis. That's when you get your initial platelets plan formacion or soft play a plant that hasn't been hardened up yet because the way it hardens often becomes a proper clot is when you have secondary hemostasis, and that's when you get fiber in mesh formation that turns it into a a better clot. Essentially on. Once that's over, the tissue will start. To repair itself will be this sort of staging, where the clot will dissolve from different anti coagulation factors being least but surrounding tissues and managing the side of size of the granted that you've got normal, normal coagulation on physiology. So in primary hemostasis happens is damage blood vessel and you get college in exposure, one with a rand factor, which is what BWF it's buying cities glycoprotein receptors on. That's when you get played, that adhesion. Following that, the platelets activate and they've got these two sacks and alpha granule and then scramble, which both have different contents. But what happens? You get from box in a two released, which causes rays of construction on the then scramble releases for two things. Such a serotonin A. D. P. S o serotonin photo causes vasoconstriction ATP causes played activation on activates for for a minute and receptors and then from all of that, you get sticky platelets. The aggregate together on become to get on combine, and that's how you get your soft player plug for me. So that's primary hemostasis in a nutshell. So secondary hemostasis So what everybody would have seen was sort of the old way of how it was represented, which was what know all that, but couple years back still was how we talk to him about it. When I was in Medical School East, there was the extrinsic and the intrinsic pathway. But now it's been that sort of the force around has been changed, and it's it's It's a bit more sort of complex about, and there's a complex amplification that sort of amplifies. It gives positive feedback to get much from been as you can, so let's walk for it. So in the initiation phase, you get some sort of tissue damage of college in exposure, which exposures tissue Fact that tissue factor converts factor seven into fat activated factor. Seven. On what that does it converts vaccine nineto Activate the fact of nine and that along with ionized calcium, because if you remember, if you remember, remember me telling you guys calcium plays important ball in hemostasis. Well, as you know, uh, other things such as, you know, bones and lots of other processes. Such your muscles and your heart and smooth muscle contraction. What specifically hemostasis Nice calcium's a ball? Because that's the free calcium that's physiologically active because 50% of it in calcium is ionized. About 40% of it is bound to albumin in about 10% is bound to other age, other sort of curating sort of things such as phosphate and what no eso ionized calcium is very important in human status, basically. So that's where you got to make sure that when someone has a massive transfusion, you gotta make sure you don't have low iron iced calcium numbers, but you can measure on the blood gas. Uh, and that's why it's sort of a port forms also important part of a major hemorrhage protocol on something not to ignore in terms of trying to make sure they're clotting properly, so that, along with active a factor nine a turn factor turn into factor. 10. A 5 to 10 a day turns pro, forming with the ionized calcium into from been foot with from men from and sort of the key bit that helps convert fibrinogen into fiber and fiber. If you mind me telling you is the mesh that helps trap things. On turn a painter plug into a proper form, a clot that will stick eso What from men does is from been. I can look back on sort of course, activation of Factor five and help with Factor five formation. A factor five or conversely also help with for a from been for for men activation information as it is, positive feedback loop called the from Been Burst. Now in the amplification stage of things which is think that sort of help wrap things up, including from Been, you've also got factor 11 A. That helps activate Factor nine, and you've also got a factor activated. Eight, which also helps turn fact the 10 into activated facts and sorry. Lots of words from my mouth is dry, but hopefully when you look back at the diagram, it will make a bit more sense. But the most important stages of this is the from the information which needs to go from been burst. Eventually. This is positive feedback loop and avenge a saying the from is important because that converts fibrinogen into activates fiber in, which helps for mom mesh on. Then, when Fibrate gets broken down by different reasons, you get fiber and breakdown products. One of them includes the diamond, which you guys have come across many times before. Um, and I'll be in the propagation stage. So that's a look. So next question six year old lady presents to her GP for her regular eye on our track. She's on more friend for a target. I lost 2.5 or range between two and three. The measure the measured I and R is for But she's well, otherwise which clotting factors does the iron or assess. And that's been the pool. Uh, I always forget into international God, Jesus Christ. I always forget you put me on the spot here, Freddie, because I always just say I, uh, International. Something ratio. I always figured, but essentially, it's another way of looking at the pro form. Been time, thank you international normalized ratio. Thank you. Okay. And it's it's It's a way of assessing the pro forma been time. It's It's it's It's Ah so moving on. We've actually got split answers again. Last minute takers. Oh, so from the looks of it, A has just edge another good equal Splenda Splenda. So the correct answer is be so. It's mostly factors that are sort of what used to be known as part of the extrinsic pathway. The fact is that you see mostly in the air, it's mostly assessing the intrinsic halfway. So let's move on to the next step. So correct answers be, as you mentioned, which is a factor one which is for a brain injury factor to perform. In fact, of five, which doesn't have a net. What have names will not names that I'm going to say. Factor five. Factor seven and factor 10 s o. Just remember one is for a bandage and two is performed. Freest issue factor. In fact, the four is ionized calcium, so iron are on activated. Partial from what plastic time. So I already mentioned measures those things. A PT measures what's in a so that's been used to be known as the influenza pathway. So looks a factor. 89, 11 and 12 on I and our so essentially what I in our is it's a ratio of the patients perform in time to a normal what's expected to be a normal performance time, so a normal performance time roughly around 11 to 13 seconds, I want to say so. It is a ratio between whatever the patients actually perform. The time it's between that and that gives you your iron, are and you're in our, well, whatever you want your eye and are to be for patient bull. And it's measured for warfarin, for the most part. Or, you know, and when you're looking at different things, like severe liver disease or when you're looking to see if patients crossing I'm normally for whatever reason and an eye on our target depends on what the patients taking it for. So a patient with a F typically a target would be 2.5 between range between two and free. But if they've got a mechanical heart valve, say, in the Arctic area, that would be higher. If they've got a mechanical heart valve in the mitral area will be higher than that, and vice versa, depending on if they have, you know what sort of our place from their head or whatever other thing. That's so I and our targets depend on what d what it was started for in the first place. So question number free. A 25 year don't present CED following excessive bleeding Post dental extraction Hey is otherwise normally fitting. Well, hey, states, His sister had a similar issue in the past. Which bleeding disorder this this patient most likely have or demon logically wise. What it one of the most common meal likely to have just admit everybody. And that's but the pull up. Okay, so the majority of you all's correctly. The correct answer is born with the brands disease. So in terms of bleeding disorders in terms of what's so, this is specifically for the UK I'm not talking about anywhere else, so him fully a second most common bleeding bleeding disorders. Hemophilia be third most common form. Willebrand is the most common bleeding disorder. A factor. Five. Leiden is a pro, quite a disorder, so typical history run bad disease as well. All of these is so you know, bruising and the success that extend them 1 10 minutes being following dental extractions. But it depends on the severity of it, because there's different forms of form Willebrand's disease, which are, you know, going to go into. But the severity depends on which form of warm winter brands disease that you have. Um, what symptoms you can experience so usually bleeding into the joint and stuff. It's unusual for one with the brands disease, but if you have, the more severe forms of remembrance is you can't seem bleeding. This insurance and other more severe bleeding so quickly and, as mentioned, was comin in. The UK is 11 around disease, followed by hemophilia A And then he must be so just a little table, which I used during medical school to represent for what sort of you want to remember. So hemophilia A is deficiency of fact. Eight. Hemophilia be is a fiction is a deficiency of fact. And nine on from one of our disease is deficiency of vitamin A brand factor, as in the name suggests, and in terms of inheritance patterns, so X linked is working. Ophelia and hemophilia be so typically it would affect the males more because remember, males have X y ladies of extracts so they ladies could have a normal X chromosome. But with if men get it, they'll have that 40 x Kroger Oh comes in and will carry on with it. And that's why, in the clear in the vignettes, one of the things was that his sister was affected, which is this is more on also subtle, dumb, dominant inheritance pattern. Possibly if you were, if you really to try and extracting instead of an X linked pattern because his sister was affected and in times of one of these, so all of these effects factors that are within the intrinsic pathway. So if you remember the activated partial fumble plastic time, what it measures is factors. Eight. Sss fact eight factors nine Factor 11 on factor 12, which is a part of the in the Lexapro. Use the nose intrinsic pathway. So if you remember him for the effects factor factory hemophilia be factor nine on a woman about since he's a little bit of factory because of how long will the brand factor effects and is joined with factor eight. So all of them increased the a PPT time, but they shouldn't affect the eye. And our, uh and that's see, I can see few things and on is it incorrectly? Think of the cost. So yeah, we'll we'll come eso Andrew will come back towards towards the end. So it's it's what it used to be. Four does so again. It's a simpler way of thinking about it, but it's it's it's not a simple as that it's more long lasting initiation propagation under and the, you know, an amplification face. But we can come back towards the end and we'll make sure to touch on the picture to explain in a bit more detailed towards the end promise. And you can hold onto that. So moving on to the next it a 35 year old gentleman presents to the E. D with a red hot, swollen leg. His FEC and CRP are normal F b c. I mean for blood count, which includes the hemoglobin whites are club platelets on, uh, white cell sort of break down and crp being one of the C reactive protein. One of the inflammatory markers sed both normal. However, he has a positive d dimer. He's otherwise normally 15. Well, what is the most likely Procardia coagulant disorder that this patient could have and let's bring up the pool And I promise you it simple for now, guys. But the next half is gonna be the next office. Going to be a bit of a headache. Probably got split answers again. Actually, no. Let me answer. Question. Cecilia, Just a second. Sorry. A carry. Uh oh. The rest of the question. A moment. So the majority of you have answered back to my lunch is incorrect. Answer. Um, so it's still a little bit about it. So in terms of proteins and knowing your sort of things that are involved in anticoagulations controlling or making sure you don't over crossover crack in it because the body has a balance between forming clots and trying to dissolve them clots. Because if there's a miss balance, if there's more clotting, you're gonna form, you know, arterial venous thrombosis that could need to, you know, beating his Penis strokes on my way over. Those clots go off in the scheme and organ damage. Or conversely, if you have too much anticoagulations as you mentioned, you're gonna have bleeding on. So in terms back light and that's the most common procoagulant. This order in the UK and essentially what it is, is it's fact it's a factor. Five that's resistant to the effects of protein C and protein c is is something that's part of anti coagulation like stops you from over clotting and when you factor five Leiden and your resistance that I don't know what liven means. But Line is a Dutch currently placing it. Zetia the medicines. I think that's what that might be. Why it's called lightens. I don't actually think it has an actual meaning to the word someone knows they can tell me. In terms of antique wagon proteins, there's protein C and S s. Oh, they're both vitamin cane dependent, Which is why you know, things like vitamin K are given, uh, to help. Sort of sort of. What's the word I'm looking for? Head. I'll come back in a second, but the point with factor five Leiden this it's resistant to the antigravity. In fact, the protein C So that means you're gonna get more pro coagulation going on in terms of bleeding. This in terms of a procoagulant, this one is that should save it all. So procoagulant. In fact, my lights, most common C are unable to calm. The fact is inhibited by, but you see, it's autosomal dominant, and you'll find that the April taking kind will be decreased protein. CNS will sort of deficiency. We just increased undergrad in proteins again autosomal dominant inheritance parents. And that's the next most common between those two on sort of decreased, decreased a time. So, you know, be more sort of procoagulant going again. Anti from deficiencies Next 90 Forman effects multiple multiple clotting clotting factors. So if you have decreased anti problem in again, you'll be clotting a lot more competitive. Some of the other diseases again autosomal dominant practical the ultrasound abdomen and pro funding mutations. When you have access performed in formation again or some dollars and again, the increased the 18. I think it really could say I factor five items discovered the university of Lighten in the Netherlands. Yeah, such Yep. Thanks, guys dot City because I'm Dutch. That's why you recognize it from Okay, so we've gone through the easy bits of this now, on to some of the questions from before. And then we're going to go through the most distal court half of this half of this lecture, which I suspect it will be much more interesting. So some, but it looks so so it's no with no incorrect to think about the secondary hemostasis in terms of the extrinsic entrance of common pathway. It's easy to think about it that way, but it simplifies things a bit too much. And now, as I said, the research is moving more towards that. That what I've showed you before. So if I go back, research is moving more towards a model that looks like this fit, which would physiologically Fitzmorris what's actually going on in the body compared to just, they're being intrinsic and extrinsic pathway that the some links between the factors like the amplification stage and some crossover between the two. So that's why they're moving a bit more towards towards this. If that sort of makes sense, Andrew, it's It's simply to think, in terms of extras, again intrinsic pathway in terms of iron are and the activated partial from your past in time because of the fact is that it looks at and assesses and measures. So if you want to remember it like that, that that makes it easier. But I would like I said, the models are moving more like this, busy a large ically, especially because of that from been burst. Being important like I said that positive feedback loop between factor activated factor five A and from, But it is really important for sort of like I said, helping you form a good big clots. Essentially. So that's why this mortal makes a bit more sense. Uh, playing tennis outside, extrinsic. Thank you for that. A partner. What other questions have you had? Yep. Thank you. Fracture five. Leiden was raised. That a bad choice of the dentist? Jesus. It's okay. Okay. Um, so let's go on to the morgue. What I think is the more interesting half of this topic. Because I could send us lots of things you can cover, and quite a bit. It's like she's from the side Femia from the site of Penis. And if you have things, But I think the things that aren't covered or least that one covered as well for me in medical school that I find Mawr interesting, um, or relevant to clinical practice. But also something more difficult. Exam questions pop up about. This is the from bottle microangiography is and on Explain what we mean by that in a moment. So let's go on to the first question. So a 21 year old gentleman presents to the e t. With fever headache on photophobia. He's being treated for presumed meningococcus up to see me as part on as part of his v t e prophylaxis. Oh, give you ast part of his VT prophylaxis. He's receiving Delta parent eso low molecular weight tapper. And three days into his treatment, he's bleeding from both. It's cannula cites his bloods are seen below. What is the most likely cause of his abnormal here is all too. Excuse me. Acceptable. Oh, sorry. Let's do that again. Yeah. Good. Okay, we have a split split split Lantus. Actually, no happy news from society Penis taken so incorrect on. So So I did. I did. I did. For a red herring in there with adults. A foreign, but it's disseminated Intravascular coagulopathy a k a d i c, and we'll break down. Why in just a moment come back to the blood in a minute. So, um, correct answers. D i c so d i c think of it as consumption. Quite good apathy. So there's both increased risk of bleeding and for both cysts, particularly in acute d i c. So that's different type. There's a chronic and acute. I'm looking a touch of chronicus much but the acute d o. C, which is what happened in this case secondary to meningococcal set the senior increases the risk of bleeding from both because essentially using you're inappropriately clotting and forming from forming sort of little from your basically forming from both cysts and those could be sent off to the body anywhere else. Microphone Michael from bosses and the body all across the sort of microvasculature on using up all of your platelets. But you're also using order up on one of your coagulation factors as well. So that's why you get a from both side opinion up as well as a derangement in iron are which just see sort of. You know, Like I said, those extrinsic regulation factors are getting affected and your A PTT is also affected an increased which was just that your intrinsic coagulation factors. So this graduation factors being used all across the board and if we go backwards remember important part of the last part of the the final part of sort of secondary hemostasis you get fibrinogen being cleaved into fiber in which forms the mesh now where the clotting you're gonna have lots of fibrinogen being used up. So your forehead village in stores will be down in D I c. On because of that, because your former more fiber and and you also, you know, forming more. You're gonna be forming more breakdown products. And that's what you get increased D diamond, because D dimer is a breakdown product fibrin on In terms of the blood film, the blood film is the other clue. So when you're looking at the blood from you get something called skin skin sites. So what sketch the sites are is they're fragments of red blood cells. Break is basically broken up red blood cells. And the reason that happens is it's it's known as a micro, Uh, and so it's not as a microangiopathic hemolytic anemia when you see these skin sites. And the reason why is because you have these mini from boxes of problems run around that sort of damaging the inside of the vessel walls. But they're also very rough and literally red blood cells. The brush pasties literally get broken and shared off, and they break down. And that's what you could get anemia with it as well for that reason, because the bleeding but because of red blood cells actually broken down. And that's why you see skin sites on that, And that's basically means you're seeing MICROANGIOPATHIC, um key. Miletic anemia. Red blood cells that have been broken down by mechanical force is essentially because of these from lots of from buses that are around the the's. Red blood cells are flowing into, so it's called consumption quite a few because it consumes all of your regulation factors. And that's where you get higher and Ohio pretty low fibrinogen. But similarly plates are getting used up because the initial primary hemostasis imagine that's from this is being formed. That's week from both sides. PENIA. You get anemia because of bleeding azelas they anemia that we've mentioned as well. So it's a combination of these things. Let me postop the feedback because someone asked for, uh, do that in just a second if you hold on Island. So as I've mentioned, remember for acute I d. I see from the cytopenia. Higher on on a pretty high dose for low fiber engine and blood for motion are BC fragments A K skips A sites and we'll come onto why it wasn't the rest later. So little bit more about the I see. So the I see is a chemical and the border diagnosis. It's a systemic protesters. The said that causes from both sides and bleeding and a t m. A is a from from about IQ micro uh, micro and Angela on angiography. And what that means is blood vessel walls, for whatever reason, have been damaged on these little fungus is hanging off of a band and, uh, causing a little bit of having, basically. And there's lots of things that can do down one of the things that can do that is D I C. So that's what I've from about a micro and you're on Geography is on many diseases grouped under that S o. D. I. C is associate with microvascular for my eyes. You mentioned it contained fiber and as well as platelets, which is how it differs from the other types of tm. TM is because the other types team is caused from the cytopenia and anemia, but they typically don't affect your coagulation factors. It typically spare the fibrate and all the other coordination factors don't get so you usually have a normal iron on a PTT in other TMS. But in D. I see it's a consumption, quite tomography effects, all of them and things that cause acute D. I. C. Which is a dramatic thing where you see the dramatic bleeding and from both sis is acute. Myeloid leukemia is You can see an intravascular things that cause intravascular monetise, particularly a B o humility reaction. So I you and you give someone the wrong blood group. They get hemolytic reaction because of ab oh, in terms of maybe your blood group in the major blood groupings, severe trauma can do it specifically head trauma or multi body trauma. And in terms of chronic, the I see, that's mostly the issue with that isn't bleeding. It's more clotting related, and that's typically related to malignancies. And those, um, using, producing a dino carcinoma. Swings that include that are pancreatic cancer, lung cancer, ovarian cancer, thinking about yeah and breast cancers. Those are sort of nuisance. Producing a dino carcinoma is that you're thinking about investigations wise. If you're thinking about someone with the I see, particularly in the setting of sepsis, which is the most common reason, particularly bacterial substance. But any anything that causes sepsis such as, you know, fungal, you know? You know what? Whatever. Whatever the cause of agent is, that's causing, you know, a mass really reaction it can cause the I see you want to get FBC Like I said to look at the platelets because, of course, from the cytopenia, you want to look at the coagulation I and all and a PTT gonna make sure your fibrinogen and d dimer I either gonna have low for a minute because used up in high d dimer because the breakdown products of the usage of our bone isn't you want to get blood from took a discus. The sites now in terms of causes, I can't think of any good way of remembering it. If you remember Moist, I don't know. So there's malignancy. There's obstetric, So particularly amniotic fluid embolisms. Our associate and help syndrome also associate with a Q D I C IV Melissa specific in a B or major blood group in types, sepsis, as we've mentioned in trauma, specifically, if the major major trauma or if there's head trauma associated and features include from both sides and bleeding. And the complications are if you're throwing off from like, they can go anywhere in the body and cause organ injuries, a conflict, your kidneys. You know your brain, your your gut, your central nervous system. They can go whatever on a specific complication of it can also be something called purple a four minutes, which is sort of severe. As it suggests, severe bleeding causes necrosis of the skin, which has a little bit of a different management. But anyways, the whole point is you treat on the line cause and get supported care based on what organs are effective. So sometimes if they've got severe a k i liver damage. Whatever is, you may need to give you support, whatever. Whatever it may be, consider transfusion of blood products. But that's not particularly routine. If the fibrinogen is less than one, you want to consider giving Cryoprecipitates a replacement for for binge. And if you replace that first on the pro form in time in the a PTT are still high, you can consider things such as F p f F P P, which will replace some of the coagulation factors, but it's to reduce symptoms. It's not to normalize the tests. And if they've got pop performance, I eat severe bleeding skin. The crosis. You wanna administer protein C? Let me just post up the link if you give me a second. Where metal? Just a second, guys. Uh, pump, pump, pump, pump. Sorry, guys. I'm just gonna post up the nick ahead of time. I usually have it opened, but this time, okay. So opposed to feed back link up early and guess anybody needed to go. You go. So I hope that explains d i c. In a nutshell. So as I felt how a difference from other teammates other from about eight micro angiopathy I eat those pathology that I've mentioned by the vessel. Blood vessel walls are damaged and have micro from by running around on but in them consumes the coagulation factors. A z Well, it's causing her from the cytopenia and it can be acute or chronic. So next question a 27 year old gentleman presents to his GP with fatigue, abdominal pain under rash over his trunk. On examination, arrest Do Russia peers to be particularly he states he was in hospital recently were in front in the front area bowel disease flare up and had received Prophylactic Dalton partner 14 days earlier. At one end of his admission. He is otherwise a free Brown has no other symptoms. Is f b. C. Was in week. Earlier, the GP had found some abnormalities and following hematology advice. Coag d dimer five engine on but film have also been sent. What is the most likely cause of hairs of normal? Here? Results. And that's POSTOP report. Okay, so let's see what the majority of your answer the majority of your answer correctly. It is TTP from Bought it from both sides of Penick. Pure, pure. So mostly you're not unless and that's not going to be because the icy came up. It's not going to be the I see, but it's also not D i. C. Because, um, remember, it's a consumption quite good dot professor, for the most part and acute the I see, at least you would get consumption of those quiet a shin factors where the eye and I would be raising a P T. T. A. P C t would also be affected, which it isn't in which it isn't in this case. We are still seeing schedule sites because remember, from lot of micro and drop of these, as I said, cause those blood vessel damage is and those micro from by and it's blood blood cells. Brushing past then and getting shared off of mechanical force is that it causes the scarcity sites, those fragmented red blood cells. So it correct answer is TTP, so it's similar to the I See, As I mentioned, it does not consume crackle. If you cation factors and it rarely involves the kidneys, it will. It can cause an organ damage, but it's rare that you see in a K I with a T t. P specifically. So in terms of DDP again, you'll see from the cytopenia, usually a normal iron on a PTT. Unless they're on medication, that would mean otherwise you'll see a high or normal D dimer and normal find Benadryl on Brought for Morgan shows RBC Fragments because the type of tm A that can lead to microangiopathic you knittig anemia because of the blood cells sharing off against those micro from by So TTP is a medical emergency on it's caused by a deficiency. So what I want you to remember is Adam's T 13 TTP cause Adams t. 13. So that's a type of protease on when it's evolved in. Involved in, Essentially is it's accumulation of very long, sort of have a deficiency of that 11 of brand factory form, these very long change chains and continued to basically form on because that more platelets are going to stick to it. So if you have a deficiency of this protease protease mean cleaning, cleaning things is going to be mawr, these long chamber benefactors trapping more platelets and causing these micro from by essentially so, as I mentioned, is the sort of formation of platelet rich microphone by that can lead to fumble cytopenia on M A. Hatred microangiopathic him. He came a little anemia and as a keep okay bank hammering this into you guys, it's zed blood cells brushing against those microphone buy. It does damage blood vessel walls, causing red blood cell fragmentation, which you pay is on the blood film escapes the sites and we can be acquired, which is much more dramatic in terms of its presentation, which related information of an auto antibody to add, um, Steve, 13 or could be hereditary, which is rare, er, and that's little gene mutation rate of Adam's t 30. So when you suspect somebody has TTP so first seem to look for the features, so have they got features on blood film? I guess the sites have they got from a cytopenia, you know? Are they bleeding? Is there organ involvement? You have They got, you know, CNS, you know, for for normally whatever it is any sort of focal neurology. Is there gastrointestinal pain or involvement, which was, in desperation case, the abdominal pain? But you also had obviously an IBD, so it could be that as well. And renal woman's breo. I've mentioned investigations wise you're doing FBC coagulation Going to hemolysis Labs A Z well, which includes things like LDH, which is elected dehydrogenase, which is contained within red blood cells. Have lots of blood. Vessels have been broken down higher lactate dehydrogenate. If there's more blood cell breakdown as well, you'll get things like Billy Rubin, which is formed from the breakdown product of hemoglobin and your specific get Mawr indirect. Billy Rubin I e. Uncontradicted the type that's bound to albumin instead of conjugated Benny Ruben, which is formed after it's congregated within the liver. Um, and again I mentioned a blood film. And then, if you have high suspicion for T TB, you wanna do some Adams t 13 activity testing. And if there's less than 10% that heavily activity of Adam's to 13. The heavily supports the diagnosis of TTP, basically. But the way you calculate that pre toss pretest probability is by using plasma scoring passing. Scoring essentially, is the scoring towards I've mentioned that looks the likelihood of someone having TV based in the clinical context that they've come in with. So it's got platelets less than 30 if they've got signs of hemolysis on the policies lab Active cancer, which has been sort of or received treatment for the last 12 months. If you got solid organ of some cell transplant, an MCV less than 99 or less, the more 990.5 as I mentioned, it doesn't typically effect coagulation factors and a Karate Lessons 177. It typically doesn't cause renal entries what that suggests. The higher the score, the higher than likely had. Someone has TTP. The more likely should be doing Adams T 30 testing and involving hematology is the just of it and treatment. The mainstay of treatment is someone confirmed. TTP needs plasma exchange. That's the main treatments He's involved. Hematology. Early other things you considered depending on the plasma scoring is things like like a quarter coins on toxin. But possible exchanges, the mainstay of treatment did you do to do so, uh, moving on. So a nine year old chart presents non specifically unwell to the emergency department. The mother stated she had seen some blood in her child's urine. The urine was dipped. It was positive for blood and protein. The mother father added. Her child had recovered recently from about of bloody diarrhea two days earlier, but otherwise normally fit. Um, well, the bloods can be seen below. What is the most likely cause of the hematological abnormalities on mayor is, But let me put the pool up, and then I'll answer the question. No, uh, no. Uh, no brownie points for getting this last one. Correct. So the correct answer is humility. You remix syndrome specifically all most likely related. Teo, she get a toxin producing ico. I stepped hate us because of other causes of pictures which I'm going to, But looking at the bloods again, they've got anemia. You've got a low platelet count, which is a which is what a wheeze tm a disease of these from lot of micro angiopathic disease will do the wall cause, um, from both sides opinion and he is sort of a microangiopathic hemolytic anemia, the an RNA PTT are normal, as I've mentioned, so it's not causing consumption of coagulation factors. Fibrinogen is normal again. These arms raised because of information. Probably it's the diarrhea, or this is well on that in the blood film. They're sketchers sites again, as I mentioned, which suggests that there's a break mechanical breakdown off some sort breakdown of red blood cells going on. Um so, as men should act on 60 minutes of your neck syndrome so specifically, it's commonly due to step should get a toxin. Producing coli is more common in younger Children less than 10 years old, but particularly less than five, but can also affect adults, but it tends to be sort of not as commonly seen. But there are other causes of hate us other than the cold night, but they're less common, and they include none infective causes such split. The compliment. So we're specifically would she get a toxin producing ICO like a zit? Mentioned you get again from the cytopenia normal iron on a PTT high or normal D diamond long from diligent, not feel more short of skips a sites renal involvement is very likely. So that's one of the things that the friendships from TTPTT psf mean or involvements less likely hate us. You're in. You're in excellent drum. Renal involvement is much more likely, which is when you get anything from a spectrum of just protein urea to, you know, Frankie Material and, you know, put a million other bits. And you know the question. I ask, What's for steak? A. Just lift. It has, um, in recent bouts of bloody diarrhea, particularly in Children. So, um, as mentioned, there's other types of it just is a compliment. A compliment mediated Hate us, which is four to be compliment induced. That's a nun effective sort of a more common known effect, of course, but if you're looking at diarrhea or step, you can get none bloody diarrhea initially with a sort of this sort of colonized to get toxic called, I producing bacteria that you can get. Sorry, sugar talks, and I keep saying Shigella apologize for that. I mean, sugar talks and, um, so initiate starts of his none bloody. And then it will eventually turn into bloody diarrhea and initially a prior actually during the early stages of it. On as a mentioned it's sugar producing sugar toxin producing E. Coli, and it's two types of sugar toxic that stocks and one toxin to toxin, too, is the one that causes more trouble than talks in one. So if you remember sugar toxin, too, is that particular trouble? Someone that's mawr associated with hemolytic you remix syndrome caused by E. Coli, And this is tried of a nun analytic anemia. So the way you know that and anemia away this acidy nine years none immune is by doing a that or a Coombs test. I won't go into that too much, but that's the way that you discuss it. You looked against the four most cytopenia, and it's heavily associate with kidney injury. She mentioned about It's demographics typically happens five. Today's post sort of onset or around the resolution time of diarrhea, and that's typical Hates us, which is usually caused by step or shigella. She gonna as well versus a typical he just could be things like noneffective compliment, immune mediated or other types of bacteria On whole point of supportive care. You transfused blood if they need and you do flu placement if needed, provide all conservatives need a natural to control the BP. And if the C. N s involvement you can consider things such as monoclonal antibody such as a code is a map on this is from up to date to show you the sort of timeline for a specific e stack or should get s o sugar toxin producing coli. So you know, you get the period, get affected, and then eventually you start getting symptoms of diarrhea, abdominal pain, vomiting three days later, you typically, that's when you start to see the bloody diarrhea on either sort of the diarrhea can improve, or you can develop hate Shoot s in about 15% of patient. That's the sort, of course, but the majority of patients will recover from that sort of diarrhea on the last bit because it's the last one left of the ones that I want to mention to be amazed. This hatred, which is obviously heparin induced from a cytopenia and specifically that's caused by pay effective for forming a complex with heparin, which is fueled as a foreign body. And because of that, you get this I G H I t antes, or auto antibody formations on these antibodies bind on activate platelets causing from this formation. So that's the sort of pathophysiology of HIV, because this you get a rapid drop platelets and causing from both sides of penia eso. From my information on, this usually happens 5 to 10 days after exposure, which is why in this thing, yet I put specifically someone three days after exposure and someone 14 days after exposure, because it's not within that typical sort of timeline following exposure. But that can be the lake presentations. It's not impossible. And as mentioned, you'll get from both sides because of pain activation and these from biking cause and organ damage and a schematic in effect, any organ again, and you get bleeding, which is likely related to anticoagulate that was given. But you don't again again as mentioned, although other ones except for the I see you don't get this consumption of coagulation up Lemont's. You won't get a raised a PTT or, you know, unless it's related to anticoagulate that you've given. And there's two types of hit. There's hit Type one, which is a mild, transient drop you don't have to worry about. That's not clinically significant happens in the first two days after heparin exposure. Usually. And there's a more significant dramatic hit, Type two, which is the one that you worry about, which has caused that clinically significant syndrome that we've talked about your antibody formation complex with heparin. And then you get this I G antibodies formed against it. Eso features include from Moses and from the cytopenia. Beating is usually uncommon and end organ damage because those from both is going off wherever there which whichever organ there affecting causing the scheme. You're on a diagnosis. Why step in the The plates are less than 100 50 or decreased more than 50%. You get a venous or arterial from both sis. You can get injection site crosis in the terms of confirming that you do some antibody testing such as ELISA, and you could get constitutional symptoms such as fever, fatigue and just generally speaking, feeling on, well, it's more common with actual happier, and it's less likely with the low molecular. It happens. But it can happen with the low molecular weight Heparin's on that usual for Modica Micro Angiopathic disease is in a nutshell. I hope that explains those ones. That's why I found them much more interesting to cover, because I think those things come up in exams that they probably don't get taught as well at medical school. At least I didn't necessarily. So let's post up the feedback. Did anybody have any questions? I'm sure you do. I hope that was hopeful. Yeah, it's very. It's very interesting way actually had someone recent. So the first reaction recent had someone with, um set the see me are secondary to we. Did we? We don't know. Sepsis, query source. And a couple of days later, that platelet counts are dropping to 57 on what happened was the first things we fought was Is this d I see. So, you know, I ordered all those tests. You know, the blood from to look for this case a size. I ordered a coagulation tests. See if the NIPT were raised on, like, the five minutes in to see if that was consumed on. We looked at a d dimer to see if that raised on by A were and they were raising there were affected, but he was okay in that moment. Okay, in that moment of time, but it was D I C century. And the other thing we consider was happen induced from the site opinion because we've given adult parent and is roughly about 4 to 5 days later when he started getting this low platelet count. Uh, since I was a little bit weird, but anyways, so someone wants me to go over how heparin works. Yeah, Go over. How happened Looks. Let's go over anticoagulate and doac. So let me start by reminding you guys of the sort of dull axe. So within the dough, acne is the name of what factor it inhibits. So heparin church typically inhibits anti from been free, anti from and free, as I showed you before affects multiple crossing factors. So because Auntie forming free gets inhibit eso because what's what I'm looking for? Sorry. I'm getting a little bit confused. Hold on. I'll remind myself just a second uh, dexa bon one factor. 10. So dough axe wise apixaban of rocks about our factor. 10 antagonists Because in the name, they've got X and they've got a n which means factor 10 antagonist So apixaban on river broke Saban Schools Factor 10 antagonist, which is in their name X a B exit agonist uh, have a little look. So trying to remember which clot in fact, the heparin effects. It's related factor. 10 Again. I'm just reminding myself of the crime patients. Let me go back to crackling cake regulation casket, cause I always remind myself you put me on the spot in terms. Physiology. A good question. Let's go back and remind myself before anybody answers the question. Nobody answer. The question is, I want to try and get off my head. That's the best way to remember, Uh, let's have a little look anti from bend. So I believe happened in heparin, specifically the low molecular heparin's effect factor. 10. But pepperine, it's effect. I believe the effect from men or anti From what I'm gonna have to have a little look. Can we need you guys remind me if that's all right. I have to Google. This one look happy. Can is, um so long term memories. So the mechanism of heparin is anti from his anti from been free relates anti fungal free, relate related in mainly bum bum bum bum bum. So many act by X elevated range so enhances anti from been free activity. So yeah, it is anti forbid free activity related and the low molecular weight Heparin's inhibits factor. 10. Similarly, to how rivaroxaban it picks Amanda's. We should direct or anticoagulants. I hope that makes sense. I don't remember that. That makes me feel a little bit better about myself. Anybody got any other questions? Oh, yes. So special. Thanks. Unfractionated Happier in effects. Sort of enhances anti forbid free activity on a low molecular It happen effects Fact that animal specifically inhibits factor 10. I think this is sort of history's first I've ever finished on time. Warfarin is a vitamin K antagonist. So do you remember how I said that? Are, um vitamin k dependent procoagulant switch our protein CNS which inhibit factor five. So returning So warfarin is with me. Can't I go next head inhibits vitamin K. Because of that, that means that protein protein. CNS, which are the procoagulant, can't function properly, and that means there's less inhibit inhibition of the coagulation factors such as factor five and hence that causes bleeding doesn't make sense. So that's why, for reversal, we can give IV vitamin K or something's really serious, and we need to invest being quickly, we get PCC, you know, performing complex concentrate. Brilliant. Find a Z usual. I'll be posting up the stuff tomorrow. This was interesting lecture for me. I hope you guys have enjoyed it. I know the beginning was simple, but I hope the TMS on the eight days which hopefully drilled into you in terms of times, make make a bit more sense because I thought those infants I struggled with that medical school in terms of, uh, quite a nation. Stop those questions. I always got wrong. Always at least thank you dot Thank you. Bring it. So tomorrow we got the last lecture of this Siris, which will be lft is covered by Jack. So please join us a six pm again. I'll be here at six PM Co hosting is usual and trying to answer the best things questions best I can please fill out the feedback. Please join our pages If you haven't already, I'm sure the majority of you are going to be a lifelong fans of the 60 and Siris. And that continued joining us in future. Maybe even joined us when your doctors at some point, um how do we How do we uploaded a ideal matter? Uh, can you elaborate on that, Danny? I'm not sure what you mean. You mean by that? Could you elaborate on that money? So you did it, and it never verified saying with everyone. Mmm. Were aware of that. Okay. We'll do. Is we'll have a little looks like there's a way of getting around that I will address that. I apologize for that. Guys, I didn't realize that. Have you had extra slides? At least in terms of catch up, content the videos on going to go anywhere to keep on that, we'll get that issue fixed. I'll have a look into that today and have have have you managed to get access to the slide, so I'm hoping Oh, yeah. How to sew guys before we move on. I want to ask you guys, this question is Well, I just ended up member memorizing some rubbish. So I'm making lots of new monarchs of things. But the quite a casket I just tried draining into myself. There's any of you have a way of remembering what? What impact is included intrinsic extra part because I just generally speaking, just try and tend to try and tend to remember. And if you have uneasiness of remembering it, uh, you did save his be, um I mean, let me see if I could make up a way. Let's see if we can make up with. So the intrinsic pathway, as I've mentioned, is 89, 11 and 12 on the extrinsic slash common pathway, which looks at, is supposed to be to five seven, I'm done. I don't think I have a way of off free. And that one is Well, I'm sorry. I don't I really don't think I have aware of Remember of remembering it out. All apologize. I've never Yeah, I've just ended up memorizing apologies. What I'll do is I'll have a little look and see if one of the other one of our other Mannix nose a good way of doing it, and then if it is high that posted up on on the instagram and Facebook page of pollen Apology sons. And I think I'm butchering your name. But no, I don't have a good way of remembering it on Get the video thing fixed, guys. Just a story. Last question again. Did you guys managed to get access to the slides? AST mentioned the slides were okay. In terms of catch up content, we'll get the video store to the videos. I'm going to go anywhere. I'm gonna have a little little find out about this whole idea, because apologies for that again on, we'll get that sorted. Uh huh. Okay, I think I would. Okay. And it there. And maybe if I find another way of making it easier, I'll do it right before the lecture tomorrow. If I can find an easy way of Remember, I have a little look online. Thanks a lot, guys. Appreciate it and hopefully see you soon to. Was there another question I just saw was lost question in someone who has minimal within a few december attend to catch up for those days? Yeah. I mean, I mean, yes. So we are keeping all the content on that. So you should be able to touch the Teo access to catch up content for all those previous lectures as well. Granted, we get this idea issue sorted, so I'm gonna have to have a little look it up. I guess you can access all the old stuff. Everything's been uploaded, so I'll make sure that happens. Exactly. Exactly. All right. Take care, guys. Bye. See tomorrow?