what's up ninja nerds in this video today we're going to be talking about coagulopathy again this is a part of our clinical medicine section if you guys like these videos they make sense to you please support us you can do that by hitting the like button commenting down the comment section or subscribing also do yourself I I really think a a courtesy and go down the description box below click on the link that goes to our website on our website if you become a member you'll have access to thousands of notes illustrations tons of quiz questions and there is even some board exam prep courses that are being made as well so go check that out without further ado let's really dig into quagalopathy all right so let's start talking about the pathophysiology of quagalopathy so when we talk about quagalopathy the biggest thing to remember here is that they'll present with bleeding right so it's an abnormality within the coagulation cascade and bleeding can present a couple different ways right one is they can present with like superficial bleeding superficial bleeding is more characteristic of platelet disorders right so thrombocytoenia or a qualitative platelet dysfunction kind of disorder and so when you think about superficial bleeding you think about pitiki you think about gingal bleeding you think about maybe prolong vaginal bleeding or heavy menstrual bleeding like in minorasia um you think about bleeding kind of a little bit longer than normal after like a minor cut when you think coagulopathy you think big big bruising or hematoma so you think about echimosis of the skin you think about hem hemthosis so a lot of bleeding into the joints um you can think about deeper bleeding like intraraanial bleeds GI bleeds and prolonged bleeding after surgical procedures so that's suggesting a coagulopathy platelet disorders again it's either due to they're too low or they're not working when we talk about quagalopathy there is usually almost most of the time a deficiency in a particular clotting factor that's involved in the clotting cascade or there's something that's inhibiting that clotting factor from being able to function in the coagulation cascade all right we can break that down into three different ways one is a defect of only the intrinsic pathway one a defect of only the exttrinsic pathway or the last one a defect involving both pathways meaning that this one involves a ton of different coagulation factors so let's kind of quickly and I'm not going to go through the entire cascade in detail i want this to be more of a recap and if you guys remember from basic physiology that you have what's called factor 12 now factor 12 clotting factor made by the liver moves through the bloodstream sees a negatively charged surface on the platelet and does what binds to it and gets activated when it becomes activated it then activates a couple other factors that are in the bloodstream the next one is factor 11 factor 11 then activates factor 9 factor 9 then combines with factor 8 and when they combine they activate factor 10 factor 10 combines with factor five and activates factor 2 you know what another name for factor 2 is we like to call this thromben and then thromben converts factor 1 into 1a you know what we call 1a a fibbrin so fibbrin and this one here one is fibbrinogen we'll bring this one over here a little bit more so we have more room to write that big frag but this is fibbrinogen so what happens is is once you have the platelet that comes here sees an injury of the blood vessel the platelet should come and stick to this area where's my marker here here it is this guy is going to come stick to this injury of the blood vessel wall and the reason why is there's this blue subindothelial collagen that the actual platelets love and then the epithelial cells release von wilderbrron factor and the platelets will stick and they'll start aggregating and aggregating and releasing more cytoines to cause more platelets to come to the area once that happens factor 12 should bounce off of that go through this whole pathway this whole pathway and eventually lead to what the formation of fibbrin what's fibbrin supposed to do fibbrin is supposed to come over here and lay down these strands that basically anchor the platelet plug down so this triggers primary hemostasis the plugs and then the coagulation factor which leads to fibbrin leads to the secondary heostatic plug if a patient has some type of deficiency or maybe not just deficiency but something that is inhibiting that clotting factor so some type of factor inhibitor of any of these clotting proteins that I mention here these primarily it does also affect the common pathway but we're talking about primarily these proteins if there is some type of two different things here one is is there a deficiency of any of these clotting proteins that are boxed in red so deficiency and clotting proteins or is there a inhibition All right is there an inhibitor of these clotting proteins that are boxed in red because if there is one of these two things a deficiency or an inhibitor then what's going to happen if I have less factor 8 or less factor 9 I won't be able to activate factor 10 i won't be able to activate thrombin i won't be able to convert fibbrinogen into fibbrin if I can't form fibbrin can I make the fibbrin mesh no if I can't make the fiber and mesh this leads to inability so this leads to an inhibition or a decreased secondary hemostasis and that's going to lead to bleeding now when we have patients who bleed again the difference in the coagulopathic patient is that it's more of that deeper bleeding but that's not always a perfect thing so one thing that we like to do is we like to get some labs and it's actually kind of cool so you take the patient's blood all right so here's the patient's blood and what I'm going to do is I'm going to take this blood and I'm going to add in some type of like activator uh usually it's like silica so that's a common one but we'll add in this like thing like silica and maybe we'll add in some other things but you're trying to add something that has a negatively charged kind of property to it when you add that into the mix that negatively charged surface on the silica basically activates factor 12 and if you activate factor 12 and you give it like calcium and things like that guess what's going to do it's going to trigger the coagulation cascade the intrinsic pathway and it'll lead to clotting but if a patient has an intrinsic defect so now you exhibit an intrinsic defect what the heck does that mean Zach come on man it's a defect in factors 12 11 9 or 8 they don't lead to if you don't have those factors it doesn't matter you're not going to be able to lead to this clotting cascade occurring and so because of that the intrinsic pathway will be hampered it'll be impaired so if you have let's say a deficiency in factor 12 or a deficiency in factor 8 you can go through this process but you'll never lead to fibbrin formation effectively to lead to a clot that means the time it takes to clot is going to be prolonged so this leads to a prolonged prolonged clotting time but it's a prolonged clotting time that is what we refer to as the partial thromboplastin time and so really this increased clotting time is particularly referred to and we'll write it here as the PTT it is prolonged so whenever you see a patient who has an increased PTT you think intrinsic defect deficiency in which ones 12 11 98 that's it it's an impairment in secondary hemostasis that's why they're bleeding i just have to figure out why and guess what it's pretty easy and we'll talk about it later if it's nine it could be hemophilia B if it's eight it could be hemophilia A or von Wilderbrron's disease and another thing is that sometimes it could actually be due to a factor inhibitor an antibbody that binds against factor 8 and renders it useless and sometimes it could be due to an anti-coagulant that inhibits thromben and you know what thrombin does thromben activates factor 8 and if I don't have thrombin can I activate factor 8 and can I activate factor 9 no so that's why it's important so that's the intrinsic defect what about exttrinsic defect so exttrinsic defect is there's some type of tissue injury and that tissue injury leads to the release of what's called tissue factor now tissue factor is also referred to as factor 3 now once it gets released by the tissues um or once it's actually moving through the circulation it's in its inactive form when there's tissue injury that cytoines will then activate tissue factor turn it into its active form right so we're going to represent this as 3A it's activated 3a is going to combine with another factor here which is called factor 7 and factor 7 when activated and combines with factor 3 guess what it activates factor 10 factor 10 combines with factor 5 and activates thromben and then thromben converts factor one into 1a which is essentially converting fibbrronogen into fibbrin man we good and by doing that you're supposed to lead to fibbrin formation because what happens is there's tissue damage when there's tissue damage you may injure the endothelium when you injure the endothelium it causes the platelets to stick because they see the subendothelial lining when that happens the platelet start forming a primary hemostatic plug via the activation adhesion and aggregation then that fibbrin is supposed to come over here and help to make what that fibbrin mesh which helps to stabilize it and form secondary hemostasis if a patient has a deficiency and I'd say the primary one here is factor 7 a deficiency in factor 7 will lead to a decrease in factor 10 formation a decrease in thrombin and a decrease in fibbrin formation and if you can't form fibbrin can you form a secondary hemostatic plug nope if you can't form this plug can you stop yourself from bleeding no and if you can't stop yourself from bleeding this is what we would refer to as an abnormality in the coagulation cascade referred to as bleeding all right or coagulopathy I'm sorry now real quick intrinsic defects could be due to inhibitors or deficiencies exttrinsic defects are primarily due to deficiencies all right so that's kind of quite important to remember that this one is usually due to a deficiency a deficiency in factor seven that is important to remember okay now here's what's really cool factor 7 is the big one that we need to know for the exttrinsic pathway whenever there's an impairment in factor 7 we can measure that because factor 7 needs tissue factor so what I'm going to do is I'm going to take the patient's blood and I'm going to add in tissue factor we don't call it tissue factor we call it thromboplastin and what this is going to do is it's going to act like tissue factor when I add that in what it's going to do is it's going to help to activate factor 7 and factor 7 should then activate eventually factor 10 lead to fiber and form a clot but if a patient has a factor 7 deficiency would it work no so in the presence of an exttrinsic defect it won't matter if you add the thromboplastin because you don't have enough factor 7 to become activated and lead to active factor 10 and so because of that what happens to what what happens to the time it takes to clot it becomes prolonged and that increased clotting time in this scenario is measured via a different type of study and this coagulation study is called the PT and sometimes what we like to do is this is measured in seconds but we can take the PT of the patient and then compare it to the PT of the standard PT in that given area institution hospital whatever the laboratory and then you take the PT of the patient over the PT of that standard and you get what's called an INR an international normalized ratio and so these are somewhat they're not synonymous in the sense of the units but they kind of give about the same concept that they both measure the activity of the exttrinsic pathway and so in this particular scenario it'll be prolonged so if I said PTT is in prolonged you would say okay that's a problem factor 121 98 if I said PTINR is prolonged you say that's primarily factor 7 if I said okay it's an intrinsic defect is it a deficiency or an inhibitor it could be both if I said it's a problem with an extrinsic pathway you'd say it's primarily deficiency which factor factor 7 all right so now we're going to talk about the last one which is a combination of both of these pathways so there's some type of deficiency that's really existing between both of these pathways and let's quickly remind ourselves again what are these pathways again let's start with the intrinsic and the exttrinsic and see how they come together in the common pathway and then talk about which ones are most commonly affected so we'll start with the intrinsic [Music] first so now with this being said we've gone through the combination of these pathways and see how we lead to the formation of fibbrin in a patient who has an exttrinsic and intrinsic defect there's a deficiency usually of any of these factors here as well as a deficiency in this and so again you can see how an intrinsic and exttrinsic defect and also just exttrinsic defect what do you usually have to have in this case you need a deficiency of the following clotting factors with that being said if I have a deficiency of these I'm going to lead to the same concept here less factor 10 less thrombin less fibbrin so if you have an endothelial injury or you have something that causes damage to the endothelial lining guess what happens you'll trigger a platelet casclet plug to form and so I get my primary hemostasis via the platelets coming here and sticking and then what should happen fibbrin should come in as we've talked about two times already and lead to the formation of the fibbrin mesh but again because there is some type of abnormality here and or deficiency I should say of these clotting factors it leads to less fibbrin and you won't be able to lead to this fibbrin mesh as a result there's a decrease in secondary hemostasis all right if there's a decrease in secondary hemostasis I bet you can guess what's going to happen my friends it's going to lead to bleeding we have a patient with a deficiency in a bunch of different clotting proteins here that's pretty terrifying sometimes it can even involve some of these other clotting proteins in the common pathway now with that being said since it's technically involving coagulation factors in the intrinsic pathway and coagulation factors in the exttrinsic pathway wouldn't we then if we took a patient's plasma added silica to it what would happen to their PTT well these are affected would you be able to activate factor 12 well if not if it's deficient would even if you had factor 12 would you be able to lead to this whole pathway down to factor 10 if you were missing or having an inhibitor of one of these no so what's going to happen to the patient's PTT in the scenario it's going to be prolonged so they'll have a prolonged PTT and if they have a deficiency in factor 7 if you add thromboplastin but they have a deficiency is it going to matter no because again you don't have the seven to be activated because thromoplastin is just tissue factor so what's going to happen to their PT INR it's going to be prolonged so when a patient has a prolong PTT by itself you say 12 11 9 8 when you say prolong PT INR by itself you say seven deficiency and if I say a increased PT and an increased PTINR you're saying there's a deficiency of maybe any of the coagulation factors in the intrinsic pathway and factor 7 in the exttrinsic pathway now that we've done this what would we need to build upon we need to build upon what are the diseases or the causes of these deficiencies or inhibitors deficiencies or deficiencies let's do that now all right my friends so now we're going to talk about the causes of defects in the intrinsic pathway so there's something wrong with 12 11 9 and 8 so when we talk about these I want you to remember that there's two types that are inherited and this is hemophilia A hemophilia B and then on top of that we'll technically include in this last one severe von Wilderbron's disease now whenever I have a patient who has a prolonged PTT my differential for inherited causes should be thinking about all right which one is it again hemophilia A B Bon Wilder Branch disease what should I look for in the clinical vignette to suggest this i want to see a patient who has a family history of some sort of severe bleeding or of these disease so really really examine the vignette for a family history of bleeding or some type of bleeding disorder mainly hemophilia A B or von Wilbr disease now with that being said when a patient has some type of bleeding like this hemophilia can actually come in two different flavors right so one is you're going to have hemophilia A and the other is going to be hemophilia B hemophilia A is going to be extremely much more common now hemophilia A is a deficiency in factor 8 all right so that's what I want you to remember there is a decrease in which factor factor 8 and again that's a factor that's involved in the intrinsic pathway all right so if you have less of him you can't combine with nine to activate 10 boom the other one which is less common is hemophilia B now hemophilia B is usually a deficiency in factor 9 so you have a decrease in factor 9 and again factor 9 does what that puppy is supposed to combine with factor 8 to activate factor 10 so if you have a deficiency of him can you activate factor 10 can you lead to thrombin and fibbrin no so the big thing for these is that these usually again you're looking for a family history of bleeding in both of these but here's another thing hemophilia is XL and so that's another really important thing to remember is that these and I'll put this up above it these are XL meaning that you really will only primarily see this in males all right so X- linked recessive disorder so that's why you really want to look for this in a in a patient who has a family history of hemophilia they're most likely going to have that as well all right if I have a deficiency in these we can see why both of these would lead to a decrease in thrombin a decrease in fibbrin and I won't be able to do what well I'll be able to form my primary hemostatic plug but will I be able to get that fibbrin which is the 1A will I be able to bring this one in here to lead to that fibbrin mesh no so this one will be okay but this one will be inhibited big thing here von Wbron's disease this one actually comes in three different flavors so there's type one type two and type three type one's the most common type two is the next most common and type three is extremely rare but unfortunately it's what we're talking about here in the quagalopathy lecture so type one von Wderbron's disease is when you have a very very low level of vondderbrron factor and you know what von wilderbron factor is supposed to do it's actually kind of cool so von wilderon factor will actually bind with factor 8 so here's factor 8 right and what this will h what will happen is these two will bind together so we'll kind of represent it like this imagine here's von wilderbrron factor and the blue and then here in this black dot or this black triangle we'll say is factor 8 all right so this is von wilderron factor and then this guy right here is factor 8 right there and there what this does is is there's a protein here and we'll represent this one let's do with pink there's another enzyme here or kind of a clotting factor per se and this one is called protein C so this one's called protein C and protein C is actually designed it wants to degrade factor 8 so it wants to degrade it but because von Wilderbonds factor is bound to it it protects it and basically it prevents its degradation so this will do what it'll prevent factor 8 degradation and that's what basically saves factor 8 and keeps the factor 8 levels normal so if a patient has a deficiency in vonddervon factor will it be able to bind factor 8 and keep factor 8 safe from protein C no and so what will happen to the factor 8 levels they will drop as well and so a patient can develop a deficiency in both the von Wilderbond factor and factor 8 in type two which is the next one it's the second most common this one is where your vonbrron factor and factor 8 levels are completely normal it's just they don't work properly so this is a dysfunctional this is a dysfunctional vonbrron factor it just doesn't work properly so it doesn't connect with the GP1B on the platelets to lead to a good platelet plug and the last one here is type three and type three is the most severe but it's also the most rare probably less than 1% of patients who can get this but if it happens this leads to no vondder factor almost zilch nada as well as almost no as a result factor 8 protein C will degrade this the son of a gun out of that thing so what are you left with you're left with almost no voner factor and almost no factor 8 so now if I have less factor 8 or worse you know worst case scenario no factor 8 or best case scenario I have a little bit of you know less factor 8 than normal this can potentially act like a coagalopathy because these are a part of the intrinsic pathway so these patients can have this terminology of a coagulopathy but oftent times more than not von will disease will present as a platelet disorder so it'll present with epistaxis mucosal bleeding minoria all right um peticia not too often will present with this coagulopathic type of presentation in rare instances it may if it's severe and you have no von wilderbrron factor to bind to factor 8 and protect it from protein C degrading it all right so if I have to determine between these two how do I really determine the difference well von Wilderbrron's disease versus hemophilia A they both have maybe in some degree a deficiency in factor 8 but really it's the von Wilderbron factor that it would be low here normal here that's the big difference all right all right we talked about these let's now talk about the acquired cases so in acquired cases this is going to be I think probably the easiest one if you see a patient who has a prolonged PTT they don't really have any significant family history of bleeding that is present um I would definitely be looking through their history for an anti-coagulant like heperin so if there is heperin use in their history this is definitely something that you want to consider especially if there was maybe too much like an overdose so if a patient's on hepin and let's say that they just get a little bit too much heperin more than they should have right right because Hepin is supposed to act as an anti-coagulant well how does it do that well basically what it does is it acts on this um protein here and this is an anti-coagulant protein called anti-throbin 3 now anti-throbin 3 is supposed to inhibit thromben right which is factor 2 so it's primarily going to inhibit thromben now thrombin if you guys know it's supposed to activate factors five it activates factor 8 it activates factor 9 it also helps to convert fibbrinogen into fibbrin so it does a lot of stuff so having a increased activity of anti-throbin 3 leading to a decreased activity of thrombin can definitely prevent clotting significantly but the other thing that can happen here is that it can also inhibit factor 9 and factor 10 and so you can get these diminished levels of factor 10 and factor 9 and thrombin but again remember thrombin helps to activate a lot of different factors especially factor 8 especially factor 9 and on top of that it also plays a role in activating factor 5 with that being said anti-throman 3 can really diminish the activity of all of these and if you look here what's the big factor that's really involved in the intrinsic pathway factor 9 so you could see some contribution there again particularly from uh the PTT but again remember that thromben is also important in being able to activate factor 5 and activate factor 8 so factor 8 is very crucial in the intrinsic pathway and so if you inhibit thromben technically you inhibit factor 8 and that also affects the uh intrinsic pathway so this is all going to lead to again what well platelets if there's an injury here they'll be able to stick but in all of these scenarios what can you not lead to the formation of you don't lead to 1A right and what's 1A that's fibbrin what's fibbrin supposed to do help to make the mesh and if you can't lead to him can you lead to the fibbrin mesh no and so then you won't able to form that secondary heostasis so this one's pretty straightforward if you have a patient who is on Hepin they have a prolonged PTT think about hepin induced coagulopathy an acquired coagulation factor inhibitor this one's really annoying but it is something that they can test for so when a patient comes in I'd say the ones that you want to look for on the exam is a patient who comes in bleeding and they're postpartum all right or they have an autoimmune disease like SLE um rheumatoid arthritis they have some type of malignancy so definitely consider this one or they're getting treated for hemophilia A and you know hemophilia A what's the factor that they're deficient in factor 8 so what would they be treated with factory 8 concentrate if a patient is getting factory 8 concentrate or they have malignancy or they have an autoimmune disease or they're postpartum and usually postpartum patients can have a little bit of an inflammatory autoimmune activity as well they may generate auto antibodies so these are auto antibodies and guess who these auto antibodies are going to be directed against my friends they're going to be directed against this guy what's this guy this guy's factor 8 and so factor 8 is a really important in being able to do what combine with factor 9 to activate factor 10 activate thrombin activate fibbrin and so if a patient has these auto antibodies and they're directed against factor 8 what am I going to do to the activity of factor 8 i'm going to decrease the activity of factor 8 so this is going to lead to a reduced activity of factor 8 and if I can't get him active am I going to be able to lead to the formation of thrombin am I going to lead to be able to lead to the formation of fibbrin no and so because of that will I be able to form a secondary heistic plug no big thing to remember as a high yield point for this one is really look about this one and what happens is you get a PTT all of these are elevated but if you introduce normal plasma to all of these patients every single one of them with the exceptions of really these two if you give them normal plasma you could actually do what in these scenarios you could normalize their PTT and the reason why is you're giving them the factors that they're deficient in in these particular scenarios if you give them normal plasma and they have antibodies or they have a drug all these things are going to keep doing is blocking those plasma proteins so it's not going to matter so the PTT never normalizes in these two scenarios all right that's a little tidbit but we'll talk about that in the diagnostic section now that we've nailed down the abnormalities of the PTT what are some abnormalities in the PTINR all right so now we're going to talk about the causes of exttrinsic defects so if you have a patient with an increased PT INR and they may have an increased PTT sometimes especially in vitamin K deficiencies but if you have primarily let's say just an increased PTINR you should really be thinking about factor 7 deficiency and vitamin K deficiency and when I say vitamin K this one causes more of a prolonged PTI INR if it's more mild or it's in the early stages of vitamin K deficiency if it gets to the later stages or more severe vitamin K deficiency it can then kind of start causing the effect of both pathways to be more significantly impacted so in these particular scenarios when I think about these this one is extremely rare so I won't spend a lot of time talking about it but this is usually an inherited so this is usually some type of congenital deficiency what happens is there's some type of problem where the liver isn't able to adequately produce enough factor 7 right so there's some type of um let's say again mutation that's occurring that's leading to the liver unable to produce an adequate amount of factor 7 if I don't have an adequate amount of factor 7 what's the problem with this well then I won't be able to combine with tissue factor lead to the formation of thrombin if I can't lead to the formation of thrombin can I lead to the formation of fibbrin as well no and so what happens is this leads to the downward cascade where I get less fibbrin formation and if there's less fibbrin formation will I be able to form that you know fibbrin mesh no will I be able to form a primary hemostatic plug yes but this is the part that becomes impaired so factor 7 deficiency is relatively rare the big differences between really determining if it's a deficiency of only factor 7 versus a vitamin K deficiency if you give a patient vitamin K factor 7 deficiency it won't really improve the reason why is vitamin K works on the vitamin K epoxide reductase enzyme in the liver if that liver has a hpatocy who has a mutation in the chromosome that makes factor 7 it won't matter as much vitamin K as you give them it's not going to make a substantial difference in their factor 7 so that's one way that you could clinically tell the difference is give them a trial of vitamin K if it improves it's probably deficiency of vitamin K if it does not improve it's probably a factor 7 deficiency and you'd have to check that level for vitamin K deficiency this is much more common so often times when a patient has a prolonged PTIR you have to kind of go down the line and say what could it be due to so there's a couple different things one is it could be due to a reduced intake um and so depending upon the types of food that the patient is taking in it could be due to that i'd say that that's usually a really really severe starvation um another potential scenario is when there is a malabsorption and I would say fat malabsorption so some type of fat malabsorption and so there's a lot of different types of disorders that cause fat malabsorption just to give you a couple of them think about it could be due to ciliacs disease could be due to Crohn's disease it could be due to um tropical sprew whipples relatively rare exocrine pancreatic insufficiency and you know what else another one is uh bile acid insufficiency so maybe if there's a stone somewhere in the um the common bile duct that can also do it so fat malabsorption is a really really big one another one is uh bacteria um uh particularly help to synthesize vitamin K in our gut if you put a patient on a lot of antibiotics the antibiotics can break down the vitamin K synthesis in the gut and that can lead to vitamin K deficiency so it can it could be due to antibiotic use especially if it's prolonged and the last one and I'd say the most important one is a drug that acts to inhibit the liver's synthesis of factors 2 7 9 and 10 and that is warrin so warin can definitely cause a vitamin K deficiency now let's think about this again patients supposed to get vitamin K via the diet so here is our vitamin K so if there's a deficiency in that part the intake aspect of it that will lead to a diminished vitamin K if the also there's fat malabsorption so you know vitamin K is a fats soluble vitamin so it's supposed to be incorporated with the fat globules so here I'm going to represent this this is our fat all right and then inside of this fat we're going to represent the vitamin K it's supposed to be a vehicle by which we transport the vitamin K so if a patient has fat malabsorption maybe they're not putting the bile into the actual small intestines to help to emulsify the fat so bile acid deficiency maybe they're not making pancreatic lipaces from the pancreas so pancreatic insufficiency they can't break down those triglycerides maybe they can't even absorb those fats because of Crohn's or ciliacs disease in those scenarios then even if this is the case where you have a normal vitamin K but you have an impairment in this process then that's going to lead to low vitamin K the other thing is is if you have bacteria so here let's represent that I have some bacteria present bacteria love to synthesize vitamin K so they actually help to produce vitamin K and this can get into the bloodstream all right so they help to make vitamin K if you put a patient on prolonged antibiotics what are you going to do to the bacteria in your gut you're going to destroy them if I destroy the bacteria in my gut am I going to be able to synthesize vitamin K no and so that leads to a deficiency in vitamin K the problem with that is is that vitamin K goes to the liver it's involved in an enzyme this enzyme here we'll represent in blue it's present inside the liver right in the apatocytes this is called vitamin K epoxide reductase you're like what the this K epoxide reductase this enzyme is involved in being able to really help with the synthesis of particular coagulation factors and these coagulation factors are as such factors two factor 7 factor 9 and factor 10 now if I have a decreased intake of vitamin K I don't absorb the vitamin K my bacteria that are supposed to be producing vitamin K aren't there or I have a drug that's inhibiting these enzymes the vitamin K epoxide reductase so I'm going to inhibit this enzyme if I inhibit these will I be able to synthesize factor 2 factor 7 factor 9 and factor 10 no so here's the interesting thing factor 7 has the shortest halflife so in other words it doesn't live very long all right I'll put t half so that's the shortest halflife meaning that whenever you produce all of these clotting factors the first one to be deficient quickly is going to be factor 7 so it's going to drop precipitously the quickest which pathway is factor 7 involved in intrinsic or exttrinsic exttrinsic so that's why in patients who have early or mild vitamin K deficiency they may only present with a elevated PTINR but as the disease progresses so here's the caveat if it becomes severe so let's let's say late or severe vitamin K deficiency what will happen is this will then start to lead to what a drop in the production of all these other coagulation factors enough that it can actually start to cause prolongation of the PTT so eventually this may cause a prolonged PTT and PTINR but usually the most common one that you're going to see is you're going to see that lead leading to an elevated PTINR primarily plus or minus an elevated PTT depending upon the severity of the vitamin K deficiency woo that was a lot right but that's the big thing so if a patient has intrinsic defect again you think about hemophilia a hemophilia B severe von wilder bronze disease I think about hepin use or I think about aquired coagulation factor inhibitor if it's exttrinsic think about a rare congenital deficiency of factor 7 it wouldn't get better if I give them vitamin K or vitamin K deficiency I give them vitamin K and they improve think about it are they not taking in enough are they not absorbing fat which needs to be used as a vehicle to bring vitamin K in or am I giving them too many antibiotics and I'm clearing out their gut microbiome or is it war use that's suppressing the activity of vitamin K in the liver sometimes you can even add cerosis into this area as well because that can also suppress the liver's production of vitamin K as well but I want you to remember this one that's the big one all right and then again take all of this remembering that these both will prolong the PTNR but in the late and severe cases of vitamin K deficiency it can start to drop these other ones more that it causes the prolongation of PTT all right we hit the last ones here which are the combination of intrinsic and extrinsic defects all right so now on to the next part which is again what happens if there is a abnormality in both the pathways and so this is when you want to think about DIC and cerosis so dissimmined intravascular coagulation this one I want you to think about in a couple different scenarios i'd say um the biggest things to be concerned about with this one I'm going to do this one a little bit odd here but we're going to kind of say like this you want to think about this in sepsis that's a really really big one um I would also be considering this in trauma um I would consider this a malignancy especially like acute myioitic leukemia um there is the variant of it the APL acute py promyio leukemia um and then the other one is u obstetric complications um particularly placental abrupt those are usually the the the big ones now what happens here in DIC is that all of these conditions in some way shape or form create kind of an inflammatory like cytoine storm so it's either a combination of really really bad inflammation um that's characterized by a lot of different cytoines um that are being released all right and so in some way shape or form this is precipitating some type of inflammatory event um via cytoines placental abruption is a weird one it actually can just directly it's amniotic fluid can activate can actually have like tissue factor in it and so you can increase your tissue factor production but basically all of this kind of inflammatory process what it does is is they're going to activate all the procoagulants that are part of the intrinsic and exttrinsic pathway so we're going to put all pro coagulants and so essentially that kind of encompasses our what our intrinsic and our extrinsic pathway so then that process is really interesting cuz because then what happens is these procoagulants in combination with platelets so let's represent a couple different platelets that are kind of moving here as well these platelets they're also going to be incorporated into this process and what happens is the combination of platelets and this increased presence or increased activity of procoagulants leads to widespread thrombosis so now I'm going to cause all these thrombi all right you're probably like "Zack you said coagulopathy bro aren't they going to be bleeding?" Yes but hold on when this processes trigger massive inflammation systemically these cytoines activate procoagulants procoagulants and platelets then lead to the formation of micro throi and I'm not talking about a couple i'm talking about a lot of micro throi like widespread diffuse all over the place the problem with this is is that in order to make the micro throi I need platelets in order to make the micro thrombi I need proco- coagulants factor 12 11 9 8 5 10 7 3 all of them I need all those coagulation factors and so what happens is in the process of making um in the process of consuming these coagulation factors to make clots I end up with less clotting proteins so what happens is this causes consumption of all clotting proteins man and so then what ends up happening is you end up with a deficiency of every single one of them that's what's terrifying and if I have a deficiency of all clotting proteins what is that going to affect factor 7 factor 3 factor 12 factor 11 9 8 7 10 2 the list goes on but basically I'm not going to be able to lead to the formation of fibbrin and because of that if I have a deficiency in fibbrin am I going to be able to form that secondary hemostatic plug so if there's an injury in the blood vessel the platelets will stick right to some degree but will the fibbrin be able to form the secondary hemostatic plug no so that's where this problem kind of exists but there's also another component in a dic is that you actually don't even have enough platelets because you consume the platelets and so technically to a degree I could even say that we don't have enough platelets to stop that clot or to form a clot and that can cause progressive bleeding so here's the really important thing to remember for DIC with DIC you consume all clotting proteins so when I look at these patients I'm going to have clotting proteins that are affecting both their PT INR and their PTT so what would I expect if I looked at these patients blabs i would expect them to have a elevated PTINR i would expect them to have an elevated PTT all right because why they're having decrease in all quality proteins that includes factor 7 and tissue factor and it includes factors 12 11 9 8 the other thing that's really important here to remember is that not only are you consuming the clotting proteins of the intrinsic and extrinsic pathway but you consume proteins of the common pathway leading to fibbrin right so what's the protein that's needed to really make the fibbrin mesh fibbrronogen and if you have widespread clots aren't you gonna have to use a lot of fibbrronogen to make those clots yeah so what happens to the fibbrronogen it gets consumed bro and if the fibbrronogen gets consumed what happens to the levels of fibbrronogen that thing going to drop the other thing is you're using platelets to make these clots so not only using clotting proteins not only using platelets not only using fibbrin but if you're consuming the platelets what should happen to the platelets they should drop bro so I got a drop in my platelets i got a drop in my fibbrinogen when you make clots you have a natural homeostatic mechanism that we want to kind of prevent those clots from continuing to propagate so we try to dissolve some of them and so we have plasminogen that comes in there and it helps to be able to activate plasma and plasma helps to try to break down some of the fiber and you get fiber degradation products one of those is D-rimer so D-dimer is kind of a good sign of a kind of what I'd say about a high clot burden if you want to think about that and so D- dimer are going to be elevated because they got clots all over the place so D-dimer will also be elevated but here's the last thing red cells they're supposed to be moving through this how you going to move through this clogged up highway it's going to come through here and just it's going to get shredded to pieces and when that thing comes out it's going to be mangled like the hamburger and so now you're going to end up with these goofy looking red cells what are these things called you got you ripped them in half they're called shisttoytes the presence of shistytes really heavily suggests the presence of a hemolytic process especially DIC so DIC in the presence of an inflammatory disease widespread clots consuming clotting proteins consuming fibbrronogen consuming platelets to make those clots leads to a subsequent unfortunate and ironic deficiency in fibbrronogen platelets and all clotting proteins signs of clots can be elevated d- dimers and ripped up red blood cells can be shistytes one other thing endothelial cells make factor 8 not the liver and so in a patient who has DIC they have a deficiency in all clotting proteins including factor 8 so this patient would also have a deficiency and what's called factor 8 why is that important i'll explain in a second with cerosis serotic patients they have fibrosis of the liver right so they have some type of fibrosis of the liver that fibrosis of the liver leads to a couple different things one is it leads to the inability to produce particular clotting factors so it leads to the decreased production of all clotting factors except which factor factor 8 because that's made by your endothelial cells so there is all of these factors that are diminished except factor 8 now if I'm not able to produce all of these clotting factors that are part of the intrinsic and exttrinsic pathway except for factor 8 what's going to happen what's going to happen to the to the actual fibbrinogen levels i mean fibbrin levels i'm going to lead to less fibbrin less fibbrin leads to less clots so now with that being said for a serotic patient they will have a increased PTINR because they're affecting all clotting factors except factor 8 they'll have an increased PTT because they can still affect factor 12 11 9 what else fibbrronogen well the liver again does make all clotting factors and that includes fibbrronogen so fibbrronogen could be depleted all right not because of a consumptive process but because of a production process all right what else platelets funny enough the liver actually makes a molecule called thrombopoetin which is supposed to stimulate platelet production and so if you have less TPO you'll have less platelets so less TPO less platelet production by the bone marrow the other thing is that the liver can lead to portal hypertension and that portal hypertension can lead to spinnomegaly and that spomegaly that big old spleen can sequester platelets and if it sequesters the platelets it can drop the platelet so can patients with really bad cerosis have thrombocytoenia absolutely they can all right what about a D-dimer would that be elevated in cerosis it shouldn't unless they have another concominant disease going on so I would say D-dimer should be relatively normal the other thing is is there any homoleysis that's going on here no I don't see any dang homalysis that's going on so there should be a normal D-dimer and there should be an absence of shistoytes that are present on peripheral blood smear and last thing does the liver make factor 8 no so what would happen to the factor 8 levels all the clotting factors would be deficient except for factor 8 so I would check this and they would have a normal factor 8 level so that's one of the big differences so when I think about a serotic patient I'm thinking about a patient that has more underlying history of cerosis right and they're going to have particular causative factors there alcohol abuse non-alcoholic fatty liver disease autoimmune hepatitis viral hepatitis increased LFTs hpatomegaly splenomegaly etc so you'll see some features in the vignette that really suggest that but the big laboratory differences here is that they're going to have somewhat of a symbol of a quagalopathic panel right via these but the D-dimer the shistytes and the normal presence of factor 8 really kind of helps in that cuz sometimes it can be difficult to discern is this a really bad serotic patient who's decompensated acute liver failure or a DIC patient all right now with that being said we've now talked about a patient who is a prolonged PTT and a PTINR and we try to more kind of so differentiate these two by a couple other factors from their pathophysiology what I need you to remember is when a patient comes in with a quagulopathic bleed what does that look like it's a good reminder here you want to look for echimosis all right so these big kind of hematomas that appear of the skin which look like this it can also cause a lot of swelling and blood to accumulate in the sinovial joints which can lead to hemthrosis which can look like this and then on top of that sometimes patients can have a lot of prolong bleeding from surgical incision sites so really you want to watch out for any kind of evidence of prolonged bleeding especially after surgical procedures all right so especially surgical bleeding the other thing is in rare cases but severe cases of coagulopathy especially DIC cerosis and vitamin K deficiencies you really want to watch out for the evidence of upper GI bleeds which can be presenting with what it can present with melanena and hemoteis or you want to watch out for hematzia all right which can be presenting via lower GI bleed and then lastly you want to watch out for any kind of evidence of intraraanial hemorrhage which can present with obviously changes in their mental status uh neurological focal deficits depending upon where it exactly occurs and headaches so these are really important things to be thinking about when you have a patient coming in with evidence of bleeding really think about these ones right here to think about a coagulopathic bleed as compared to a platelet disorder related bleeding and these are the worst case scenarios that you really want to try to avoid all right my friends now that we've done this let's now tee ourselves up to talk about the diagnostic approach i have a patient come in and with bleeding and I have to determine is it superficial the reason why superficial bleeding suggests platelet disorders if I see pitikier pipera ginger bleeding menorasia or potentially epistaxis but if I see deep bleeding I see brain bleeds GI bleeds hemthosis echimosis or bleeding from surgical sites or catheters or IVs that's coagulopathic bleeding that's something I want to think about right off the get-go either way for both of them and with bleeding you always check the CBC and get your coagulation parameters when I do that right away from the CBC I'll be able to tell does the patient have thrombocytoenia oh they do that could be the reason that they're bleeding also if their platelets are normal but they have a prolonged bleeding time not the PTPTT their bleeding time that could potentially suggest a platelet dysfunction right now if a patient has some type of abnormality in their PT or PTT despite their platelets they could still have a platelet disorder and coagulopathy that's not out of the world to see what you want to know is okay do they have normalish platelets but their PT and or their PTT is elevated then I'm concerned about a quagalopathy again check the CBC platelets low thrombocytoenia could be their cause if the platelets are normal but their PT PTT is completely stone cold normal and their bleeding time is prolonged it could be platelet dysfunction regardless of what their platelets is believe it or not usually in this scenario for perfect perfect scenario we'll say platelets are normal all you care about is what's their PT and their PTT if that is elevated we have a coagulopathy at play and we got to figure out which kind it is so say that we start off with an increased PTT and a normal PTIR what is this intrinsic defect so then we got our differential it was hemophilia A hemophilia B it was a severe von Wolibbrrons acquired coagulation factor inhibitors and hepin what I want to do is is a mixing study all right so basically what happens is you take the patient's blood all right and let's say that in this scenario you have some clotting factors and they have auto antibodies oo auto antibodies that was really helpful in acquired coagulation factor inhibitors okay and sometimes it can even be helpful in heperin because heperin actually can act as a it's an acquired coagulation factor inhibitor either way you take this patient's blood who either has heperin in it or an auto antibbody and you introduce it to normal serum plasma normal blood which can have a bunch of different types of proteins in it clotting factors if you mix these two that has clotting factors and the patient's blood that has the auto antibbody in it or the heperin in it what do you think will happen if you mix the two all that's going to happen is the auto antibodies or the heperin will bind to all these coagulation factors and basically prevent it from working so will the PTT actually correct when you mix it with that patient's blood no it will not correct this is suggestive of an acquired coagulation factor inhibitor when the PTT remains prolonged this is either that factor 8 inhibitor like an SLE RA malignancy postpartum or treatment with hemophilia A um precipitates particularly the factor um 8 precipitates if I take the patient's blood and they don't have any coagulation proteins they have a factor deficiency and you give them normal blood which actually has all of these clotting proteins present what will happen so their PTT was prolonged because they had a deficiency here all right this PTT was prolonged because they have auto antibodies binding to the coagulation factor factor 8 in this case in this one I have no auto antibodies they just don't have enough of these proteins and I give them normal amounts of these coagulation proteins what will happen to their PTT will it improve absolutely it will because now I have coagul coagulation proteins that I can introduce to start helping them to clot that will cause the PTT to actually start to decrease or normalize that suggests a factor deficiency so what I want you to remember is when you have a patient who bleeds and their PTT is prolonged you do a mixing study and it stays prolonged it's an acquired coagulation factor inhibitor if it does improve it normalizes or decreases it's a factor deficiency that's super super important so let's say that we take the patient who it does not normalize and it's a coagulation factor inhibitor what I want to do is is I want to know are they using heperin that's the easiest way to go about this are they using hepin if they are all right it's probably heperin quagalopathy done if they are not using hepin you got to think about that weird acquired one and if that's the case you got to start thinking okay could this be the you know acquired coagulation factor inhibited from SLE from RA from postpartum from them getting treated for hemophilia A those are things to consider now with this being said sometimes what we actually like to they love to throw this on the exam especially with these kind of scenarios antifphospholipid syndrome is not per se a coagulopathy it's actually more of a hypercoagulable state but what happens is it's very paradoxical when you have a patient who has a prolonged PTT and they actually have no normalization of their PTT and they're not on Heperin um and you can't really find an acquired coagulation factor inhibitor that's actually occurring here you always want to think about anti-phospholipid syndrome and what we do is we actually do what's called the um after this part we do what's called the dilute Russell Viper venom test and if the patient's PTT does not correct with the Russell Viper venom test it's because they have a lupus anti-coagulant that's preventing this and so that's really really important so if you ever have a patient who comes in and you check their PTT and it's prolonged you do a mixing study and it doesn't normalize and they don't really have heperin use and you can't fire in a fire acquired coagulation factor inhibited cause check the dilute Russell Viper venom test if it doesn't actually prolong it could be due to the lupus anticoagulant which we see in antifphospholipid syndrome that's something to consider about all right if the PTT normalized that's a factor deficiency we just have to figure out if it's due to factor 8 deficiency factor 9 deficiency or is it severe vonilibbrron disease so what I want to do is I actually want to check factor 8 i want to check factor 9 and I want to check von villbron factor activity and then on top of that I want to check that rrista to see and co-actor asset which we talked about in the platelet disorders because it's going to tell me if I do that study the uh and they don't aggregate and I add plasma rich von woodrun factor to the scenario and they do aggregate that's diagnostic of von will run disease so let's say I do this and I see low factor 8 activity that is hemophilia A if I check it and there's low factor 9 activity that's hemophilia B and if I check it in the von willilibbron factor activity or antigen activity is very low and on top of that the ristocan co-actor assay tells me that there's no aggregation but when I add the von will factor to the mix it does aggregate that tells me it's severe vonilibbrron disease all right now from here I've taken care of the intrinsic pathway what if I have just a pure exttrinsic pathway defect meaning the PTIR is elevated but the PT PTT is normal again could be congenital deficiency right that's very rare but it is something to think about but most of the time it's a vitamin K deficiency early or mild vitamin K deficiency how would I actually prove this give them vitamin K you can't hurt them to degree give them vitamin K if you give them vitamin K what will happen is if it does not improve the PTINR it's a congenital deficiency because in a congenital deficiency the liver can't produce factor 7 it doesn't matter if you give them vitamin K or not it's not going to produce more factor 7 so Ptin isn't going to improve that's congenital all right that's a factor 7 deficiency but if you have a patient who is not taking enough vitamin K in they're on antibiotics that's suppressing vitamin K production by the bacteria in their gut they have a fat malabsorption you give them IV vitamin K we bypass all of these different ways and we get it straight into the bloodstream we get it to the liver the liver starts producing factors 2 7 that's the important one 9 and 10 what's going to happen to their PTI and R it will improve and it'll start to normalize and go down if that happens it's a vitamin K deficiency boom roasted we did extrinsic if I have a patient who has a increased um Whoops all right boom roasted now here let's take a second to remember again with factor 7 deficiency again you're looking for a family history a personal history of bleeding but with vitamin K deficiency you're looking for that warrant toxicity so look for a patient who's taking warin that's a really important one look for newborns who didn't get a IV vitamin K injection upon their birth look for fat malabsorption disorder so a patient with weight loss and statera those foul smelling fatty stools and look for prolonged antibiotic use that could be suppressing their intestinal flora production all right now that covers the extrinsic pathway defects if a patient comes in and they have a prolonged PTT and a prolonged PTINR you have to come to the decision of okay could this be severe or late vitamin K deficiency DIC or cerosis and this is probably a combination of both pathways being defected guess what I should do right away i should actually do a vitamin K trial again because believe it or not anytime the PTINR is elevated you should always just kind of try a vitamin K trial if the vitamin K upon administration improves the PTINR it's probably a vitamin K deficiency it's probably a very severe one if they have both an increased PTT and a PTINR but if it does not improve it it could be DIC or cerosis so how do we really go about this remember I told you DIC cerosis we look at the PT PTT um we look at the platelets we look at the D-dimer we look at the fibbrronogen and we look for shistytes and lastly factor 8 levels so let's do our DIC panel let's check a peripheral blood smear and let's check factor 8 levels the DIC panel will give us the fibbrinogen and the dimer which is going to be pretty helpful as well so if I check that and I see no shistices right away there's no hemolytic anemia that supports cerosis if I got a low fibbrronogen but a normal d-dimer again there's no heavy clot burden but the liver isn't maybe producing enough fibbrronogen and if I have normal factor 8 oh factor 8 normal that's cerosis baby but if I look and I see shistytes present that means that there's thrombi ripping the red cells up if there's low fibbrronogen and an increased d-dimer that means I'm consuming clotting proteins that consumes fibbrronogen and my d-dimer is up because I have a heavy clot burden micro throi all over the place and there's low factor 8 levels that's dic my friend so that's something to definitely be concerned erned about for DIC now DIC also really involves history is a patient septic have they had a significant trauma do they have a malignancy like acute milo leukemia have they recently had a placental abruption and then also in their history if you ever read oozing from IV sites always be suspicious of DIC for cerosis you're looking for a patient who has underlying stigmata of liver disease do they have ascites do they have palmer do they have spider angioma do they have potentially um hypoestrogenism so decreased libido uh you know testicular atrophy do they have gynecomastia um do they have some type of jaundice so look for those things and do they have a history that would suggest that disease alcohol abuse non-alcoholic fatty liver disease hepatitis those would really lean more towards the serotic picture all right this really gives us a strong idea of how to really work up and think about coagulopathy in a true clinical manner how do we treat it though that's really important right if a patient's bleeding I need to know how to treat it so first off you need to treat the underlying disease if it's a patient has von wilderon disease it's actually kind of straightforward for minor bleeding or they're about they're they're just kind of getting um a minor procedure what I mean by a minor procedure that could really just be like you're doing a central line or you're doing some suring like um you're doing very very minor things you're inserting a Foley catheter something that puts them at very mild risk of bleeding um you could give them DD-AVP prior to that the concept behind DDAVP is that what it's going to do is it's actually going to stimulate the endothelial cells to produce von will factor and that's going to basically help with the platelets sticking here and cause that clotting to occur but in severe cases where a patient's really bleeding they got brain bleeds GI bleeds they have excessive kind of bleeding or they're getting ready to actually get a full-on surgery maybe they're getting an Xlap maybe they're getting some type of cardiac surgery you really should prevent them from having significant catastrophic bleeding and so you'll give them vonil factor concentrate and that's literally going to increase their von will run factor and help with that sticking of the platelets to the to the cl um to the actual broken up blood vessel lining all right so mild DDVP severe von will run factor now hemophilia is a little bit different we actually can again in hemophilia A we can give them DDAVP it's actually really interesting because think about it ddavp does what increases the production of von will factor what does von will factor do it prevents factor 8 degradation so it keeps factor 8 levels normal at least kind of normalish and so you can prevent them from continuing to have bleeding so it's a good prophylaxis for very minor procedures or they have very minor bleeding they're bleeding pretty bad then you give them factor 8 concentrate now hemophilia B you give them factor 9 concentrate all right because your your problem is a factor 9 deficiency the last thing that we could consider is if a patient has hemophilia A they have minor bleeding you give them DDVP all of a sudden they have severe bleeding you give them factor 8 concentrate if they still continue to have recurrent bleeding despite DD-AVP and factor 8 concentrate and then you check their actual factor 8 activity level and that's less than 1% dude there's you have to give them something that can actually act as a glue it can lally kind of act like factor 8 basically and it can help to glue factor 9 and factor 10 together and activate factor 10 and that's where this drug called imisumab comes into play it's basically kind of act like it like a artificial factor 8 to a degree except it's not factor 8 it kind of acts like it and it's a glue and it takes factor 9 and binds with it and then activates factor 10 so it kind of acts like factor 8 which is kind of interesting but you only do this if they continue to bleed despite this and this and their activity is so low that we just basically don't even give them factor 8 at this point we just prophylactically give them emismab all right heperin coagalopathy only reason we would actually reverse Hepin is if a patient is bleeding or they're about to get a super invasive procedure like a cardiac surgery any kind of surgery that poses a risk of bleeding and they wouldn't be able to stop bleeding we give them protein sulfate the concept here is hepin again increases anti-throin 3 which decreases the activity of factor 10 9 and thrombin so what I want to do is give them protein sulfate to inhibit that activity of hepin that decreases anti-throman 3 and and then basically increase the activity of these so that they can actually initiate clotting so that's what we would do if a patient is having an heperin coagulopathy we would actually watch their PTT to make sure that it's improving vitamin K deficiency is super high yield i really need you to pay attention right now if a patient comes in they have an increased PTINR on its own or an increased PTINR and PTT and you have bleeding and specifically the most common one that you're going to be tested on is Warren use when they bleed due to a vitamin K deficiency you can't just give them vitamin K only what you're going to do is if a patient comes in let's say the clinical vignette says you have a patient coming in they're on warfin and they're bleeding they have a brain bleed you give them what's called Kentra or four factor PCC four factor PCC replaces it's basically um essentially factors 2 7 9 and 10 you're giving them that you're replacing and that's going to act quickly and replace those clotting factors so that you can actually stop the bleeding right away but then you're also going to give them 10 milligrams of IV vitamin K because while this stuff is cooking and it's working you need the IV vitamin K in the background to tell the liver to start producing more factors 2 7 9 and 10 so what you're going to do is you always give both of these right away in an active bleed if the patient is not bleeding they are not bleeding you do not need to give them PCC and you don't need to give them IV vitamin K what you want to know is is what's their INR is it super therapeutic so let's say that you have a patient who has a very elevated INR but they're not bleeding they're asymptomatic they just have a super therapeutic INR it's due to warin often times if the INR is greater than 10 we give them 5 milligs of oral vitamin K and if the INR is greater than five and they're asymptomatic we can give them 2.5 milligrams of oral vitamin K all right so bleeding while on Warren doesn't matter what the INR is pcc IV 10 milligs of vitamin K not bleeding then you determine where is the INR is it greater than 10 five is it uh in this case greater than five but less than 10 you give 2.5 milligrams of P vitamin K no PCC for either of those dic or cerosis these patients can really bleed man and so we often times just do a lot of supportive care for these you can give them pllet transfusions because both of them are going to be low in platelets but we only really do that if they're less than 10,000 and asymptomatic we just want to reduce the risk of spontaneous hemorrhage or if they're bleeding or they're getting ready to get an invasive procedure and their plates are less than 50k all right that's one potential reason for the platelets again the whole point here is that you're trying to give them to increase the plates but you only do it upon these particular scenarios ffp is all of your coagulation protein so if a patient has both an increased PT or an increased PTT and they're bleeding or they're about ready to get a procedure where they at risk of bleeding you should give them FFP you're replacing all of their coagulation proteins plus fibbrronogen plus von will run factor so that they'll be able to clot if they need to and lastly cryoprecipitate can be given if they have active bleeding despite FFP and their fibbrronogen's less than 100 so in these potential patients both of them they can have hypop fibbrronmia and so if I need to give them crop precipitate I will give them that because it's very very high in fibbrronogen I'm replacing the fibbrronogen deficiency all right so again these ones really the Only way that we're treating the quagalopathy is giving them platelets because they're going to be both low in platelets giving them FFP because they're both going to be low in all coagulation proteins the only exception is cerosis is not deficient in factor 8 and then cryoprecipitate they're both deficient in fibbrronogen so we have to give that fibbrinogen back my friends this covers coagulopathy i really hope that you guys liked it i hope that you learned a lot i hope it made sense um I love you guys i thank you guys and as always until next time [Music]