Heparin | Mechanism of Action, Indications, ADR’s, Contraindications

what's up engineers in this video today we're gonna talk about heparin it's a very important anticoagulant used very commonly in medical field it's a really important one so let's go ahead and get started on it iein engineer so let's go ahead and get started on the mechanism of action of heparin so heparin is so darn cool and we'll talk about the different types of heparin but before we get into the unfractionated heparin the low molecular weight heparin and another synthetic type of heparin called Fonda paradox I want us to briefly go over the coagulation cascade if you guys remember what happens because it's important if you know the mechanism of how this actual coagulation occurs then the mechanism of action of heparin is going to be so simple and you'll be able to understand the downstream effects of it so you guys remember whenever there's some type of damage to the blood vessel or there's some type of injury to the endothelial cells or there's a hypercoagulable condition or their stasis of blood flow berkos triad right there's an increased risk of forming thrombi how does that happen you guys remember the underlying collagen is exposed what happens von Willebrand's factor is combined with in that collagen Network it's like extremely a desired by the platelets the plates will then come and angry and bind to the von Willebrand factor once they bind what happens it triggers those granules to D granulate and release adp thromboxane a2 serotonin what does that do that causes more platelets to come to the area what else does it do it also causes the platelets to start to stick to one another right we talked about all those mechanisms in coagulation cascade won't in our hemostasis video right once this happens and the platelets become activated if you guys remember they developed this kind of like negatively charged surface that negatively charged surface is super attractive for certain types of coagulation proteins if you guys remember one of the big ones is factor 12 factor 12 when it reacts with this negatively charged surface it becomes activated and then if you guys remember what does factor 12 do factor 12 activates factor 11 and then if we just keep going down this cascade here factor 11 then we'll activate factor 9 and then if you guys remember there's another molecule here which is going to be called factor 8 and factor 8 we'll talk about where he gets activated and how he comes into this we're just gonna throw him in in a different color for a second here factor 8 is also gonna be utilized and he's going to be activated in this process he gets activated through what's called thrombin and we'll talk about how but he actually is going to be utilizing the steps and i have factor 9 and factor 8 they combined and when they combine we're gonna change the color to change the type of pathway here let's turn a purple then what we do is we take another molecule here called factor 10 what happens is factor 10 he gets activated and then what happens is factor 10 then goes on to this next step where he combines with another factor we're gonna make this a different color again for purposes we'll explain why but there's another factor called factor 5 and factor 5 is going to be utilized in the step or factor 10 and factor 5 factor 5 is activated by thrombin again and what happens is this factor 5 and factor 5 a is long with another molecule called platelet factor 3 turns another molecule a really important one called pro thrombin and if you guys remember this is actually factor 2 he gets activated into the activated form of factor 2 which is thrombin now the next thing that happens is thrombin then comes over here and he actually does a couple things he stimulates the he activates factor 5 he also activates factor 8 and guess what else the son of a gun does he also comes over here and activates another molecule let's make it a different color just to make this all look Purdy it's called fibrinogen fibrinogen if you guys remember we said is a actual soluble protein but whenever you polymerize them you take one fibrinogen and you start polymerizing with a bunch of fibrinogen molecules what happens you get fibrin right and fibrin is an insoluble it's an insoluble type of protein and so it's good for making the blood more viscous and thick to help with that coagulation process now once we have fibrin we're gonna do another enzyme one more enzyme laughter I'm gonna does a lot does any guys well you're gonna see why that's important but guess what else he does he also takes another enzyme and activates another enzyme and this enzyme is called factor 13 now factor 13 in its activated form is extremely important because guess what it does it takes the fiber molecules and combines the fiber molecules into a nice cross-linking like mesh so now I'm gonna take this fibrin and this fibrin when it reacts with this actual factor 13 look at this guy he's going to react here it's going to take the fibrin molecules and form a beautiful fibrin mesh so now we're gonna get this fibrin mesh and I'll show you what that means here now I'm just gonna have imagine I make these dots like lines a bunch of dots are gonna make up a line right so again if I were to kind of like show you here that's a bunch of fibrinogen molecules I'm gonna take and cross-linked these fibrinogen molecules and I'm gonna make these nice strands that are gonna really help to stabilize this platelet plug cuz I want this thing to be steady I want to really hold an anchor that sucker in right now there's one other process that happens this whole thing if we go with the maroonish color from factor 12 to factor 11 to after nine and the combination of factor eight this is all part of the intrinsic pathway intrinsic pathway okay so again all the way when we talk about again factor twelve to factor eleven to factor nine in combination with eight when it converges and it comes down here to factor ten in this purple pathway factor ten gets activated and then activates thrombin which then goes and activates fibrin all of this process from there this is going to be your common pathway to forming the fibrin mesh so this purple is going to be basically a part of your common pathway and the common pathway is important because I'm not going to explain to you why here there's a convergence on this specific pathway well guess what whenever your blood vessels are injured remember they make another molecule here right they make a molecule here called factor three factor three will then act will then react with another molecule called factor seven and when these molecules react together they actually are going to form a specific complex here that is really good at being able to stimulate factor ten and when they stimulate factor ten what does that lead to that leads to the activation of thrombin and throbbin down to the fibrin mesh this pathway is called your extrinsic pathway okay if you guys remember from the warfarin video factor seven was the main one that was affected right because it has the shortest half-life and he remember we monitor the effects of warfarin based on factor seven through what's called the PT or the ratio called INR right in the same way we're going to talk about heparin and we're gonna talk about a very briefly about the different types of heparin but they work by inhibiting specific enzymes in this pathway here mainly in the intrinsic and the common pathway and we'll talk about the tests that you utilize it's called the PTT right the partial thromboplastin time whereas the PT is the prothrombin time all right so now that we know this basic coagulation cascade where does heparin come into this allright heparin is a very interesting little molecule so what makes it up is actually two different components let's use here red ok so you have heparin right we're gonna basically split heparin right you take it from a pig so a bovine source and what this happen is is it's king of broken onto two components one is you have what's called the unfractionated heparin form okay unfractionated heparin is there's actually two types there's a high molecular weight and a low molecular weight but really when it comes down to it really we really consider the unfractionated heparin to be what's called the high molecular weight heparin and I'll explain what I mean by that the other type of heparin is called your low molecular weight heparin so that's why we really just consider unfractionated heparin to be the heavy molecular weight heparin and the other type of heparin to be the low molecular weight heparin I'll explain why heparin is made up of two components so imagine here these little dots these are little monosaccharides I'm gonna put five of these monosaccharides together so what do you call that you call that a Pinto saccharide right same thing over here with the low molecular weight heparin I'm gonna make five little circles here which are representing saccharides that's a Penta saccharide then coming off of it I'm gonna have this specific type of molecule here which we're gonna call a gag okay so you have a gag and then you also have this other molecule here called your Penta saccharide these two molecules together make up the heparin right now the glycosaminoglycan or gag is longer in the unfractionated heparin as compared to the low molecular weight heparin it's really small that's the real big difference honestly the only difference between the unfractionated heparin and low molecular weight heparin is really just the glycosaminoglycans structure well why do we have two of them because this unfractionated heparin because of this long glycosaminoglycan he gets a little extra action let me explain what happens okay so now what we got to remember is that in order for us to be able to inhibit this process we need an enzyme that's going to oppose this right some way somehow to keep the blood kind of anti thrombotic and we talked about this in hemostasis video so if you guys remember the actual liver makes a beautiful protein here called anti thrombin 3 so this is a really cool molecule now what happens with antithrombin 3 is actually going to be very crucial that we understand this in comparison with heparin now let's imagine here we put heparin we're gonna put him right into this blood vessel wall so we're gonna say here is going to be our nice beautiful little heparin guess what we're gonna make it into an H form so you guys remember that look at that here's our heparin and we're gonna put them just like that yeah alright so we got that that's our nice little cute little half right here we'll just be cute and we'll put pepper in right and then binding into that is actually going to be this antithrombin 3 so let's put the antithrombin 3 inside of this right here so anti thrombin 3 so what happens is when heparin binds with antithrombin 3 it accelerates the activity of antithrombin 3 right what does antithrombin 3 do it does two things depending upon the size of the glycosaminoglycan which is the difference between the unfractionated and the low molecular weight heparin I'll talk about that in a little bit right now just know that when heparin binds to antithrombin 3 antithrombin 3 is going to mainly inhibit thrombin formation we'll thrombin action activating thrombin so it'll inhibit the thrombin as well as inhibit the activation of you're ten and if you think about it regardless if I inhibited thrombin directly oh that's beautiful and I do that through antithrombin 3 I'm going to inhibit that you know the formation of the fibrin mesh inhibit a clot formation or inhibit the clot from getting bigger but in the same way even if I inhibit factor 10 I'm going to inhibit eventually thrombin I might get more of a downstream of a larger effect because when you inhibit proteins farther up within a coagulation cascade you get a more amplified effect because now from me activating factor 10 inhibiting factor 10 factor 10 activates tons of thrombin and then that makes sense so if I inhibit factor 10 I might actually inhibit a ton of different thrombus whereas if I just hit him at one thrombin so that's kind of a beautiful thing with heparin so remember I told you heparin binds antithrombin three kind of like a cofactor accelerates its activity to inhibit thrombin and to inhibit factor 10 we want to be very specific though the unfractionated heparin because it has this large glycosaminoglycan that allows it to inhibit both thrombin and factor 10 so let's write that in here can inhibit two types of proteins when it binds with the antithrombin 3 it can inhibit both factor to inhibit factor 10 okay and I'll show you like a little like animation of what what I mean by this so you can inhibit both factor 2 which is thrombin and factor 10 that's a beautiful mechanism and we'll talk about how that works low molecular weight heparin on the other hand when it binds with antithrombin 3 it only inhibits factor 10 so that's what I want you guys to remember about this so it inhibits factor 10 but if you think about it it's going to indirectly inhibit factor 2 downstream from that there's another molecule I'm just gonna mention it very briefly it's called Fonda paradox so we'll throw this last little molecule in here just so I mention it so Fonda paradox is another type of heparin I'll put it right here it's a synthetic form of heparin so you also have what's called Fonda pair Knox and all Fonda para Knox is is it's just a pen to saccharide it has no glycosaminoglycans so it's a Penta sack right and all this guy really does is is he just works by binding with antithrombin 3 and inhibiting factor 10 that's it okay he has no glycosaminoglycans structure so this is a synthetic form of heparin now here's what I want you to remember it's very simple so let's understand how this actually works let's say here I draw will draw here and antithrombin 3 molecule so let's say here I have anti thrombin 3 okay so here's my antithrombin 3 molecule then what I'm going to do is I'm going to bind on to this antithrombin 3 I'm gonna put in that pin to saccharide structure here so let's say here I put on to this this pin tip saccharide structure so 1 2 3 4 5 right then looping around this antithrombin 3 I'm gonna have this tail coming out okay and imagine this tail kind of like a little dagger okay now when antithrombin 3 is activated it actually binds directly with another protein called factor 10 so you can see how with the Penta saccharide structure whenever heparin binds with antithrombin 3 it's going to directly inhibit factor 10 because it's bound to this complex but the glycosaminoglycan the longer it is the more can loop around that antithrombin 3 and inhibit another factor that's here on the back and guess what that factor is factor 2 so you need the long glycosaminoglycan and orbit into an orbit in order to inhibit factor 2 okay if you have the short glycosaminoglycan you're only going to inhibit factor 10 if you have the long leg because we look like and you're going to have it both factor 10 and factor 2 so I just wanted to give you guys a little thing there to make sense of that now that we know the mechanism of action of heparin one thing I want you guys to remember just clinically you have to think about these kinds of things couldn't clinically heparins function depends upon antithrombin 3 so without antithrombin 3 with the effective heparin even B would it be good at all no so what does that mean if someone is suffering from liver failure this is an important clinical kind of like correlation here if someone is suffering from liver failure what happens to the production of antithrombin 3 it drops and if you drop the antithrombin 3 you don't have something for heparin to bind to so heparins ability to work depends upon the production of antithrombin 3 so without antithrombin 3 is heparin even going to be able to prevent blood clots no so that is what's important you have to remember that there's another condition that you have to think about this read leads to the decreased production but what if you have a disease here called nephrotic syndrome which is characterized by someone getting rid of a lot of protein in their urine and guess what kind of protein they lose in their urine antithrombin 3 that's one of them and if you lose this antithrombin 3 what happens to the ability of heparin to perform its function it decreases because heparin depends upon the native production or amount of antithrombin 3 so if you lose the antithrombin 3 again that's going to lead to the increased risk of clotting so increase 83 lost in urine because with people in the product syndrome they have proteinuria they get a lot of protein in their urine they also lose a lot of lipids in their urine and because they retain a lot of water they're hypertensive they have a Deema okay so this is something that we have to take into consideration I really want you guys to understand again antithrombin three production or ammount inside of the body determines the overall efficacy evaporate okay now that we've understood that let's go ahead and kill these indications all right guys so let's go ahead and talk about the reasons why we would give someone heparin it's a very commonly used drug one of the biggest things that I want you guys to remember because we've talked about the antiplatelet medications clopidogrel pursue girl psyche a girl or we talked about aspirin we talked about gp2 b3a inhibitors all of those things we're talking about warfarin how do you know when you're gonna be giving somebody this medication as compared to all the other ones right heparin in comparison to warfarin is used more commonly for the acute onset of things so it's very quick acting okay so it's it's very very short acting it works very very quickly so it's more for acute types of conditions so what do I mean if someone has a DVT right you can give them heparin to treat the DVT acutely whereas with warfarin it's more prophylactic prevention right so when someone is having an acute DVT or PE hepburn is going to be the main mechanism a main drug that you're going to want to give in this kind of situation now do you give unfractionated heparin or do you give low molecular weight heparin it really depends upon the severity of the condition all right so when we're treating peach patients four who have acute DVTs do we give unfractionated heparin do we get a low molecular weight heparin do we give Fonda para Knox you can really do either one of them it just depends upon the severity of the patient unfractionated heparin is good for emergencies so the reason why is you can take and give a bolus of it right especially if you're giving like the higher doses you give a bolus of it and then after that you put them on an infusion pump which gives them a continuous amount over a specific period of time right so depending upon the severity you could you know give them unfractionated heparin but at the same time you could also give a sub-q injection and have them go home and that would be something like your low molecular weight heparin and there's actually when we talk about low molecular weight heparins I want to make sure that I mentioned this there's actually two main types that are utilized one is a little bit more common than the other but we have what's called an ox apparent and we have a nut and this is commonly called lovenox brand-name lovenox and then there's another one called adult heparin okay and again this is something that you're gonna want to remember whereas unfractionated heparin again we just call it on fracture we just call it heparin okay that's your main big big boy unfractionated heparin you can also give this one this one will be more for your emergencies so I want you guys to remember that this is more for the emergent you know serious kind of stuff like if it's a really serious DVT or PE then yet we should make sure that we keep them there put them on unfractionated heparin and monitor their PTT whereas low molecular weight heparin you can go ahead send them home and this would be something more that you can treat them for outpatient okay so I just wanted to make sure that we mentioned that so it can be used for acute DVTs and the same concept here if someone is having a DVT remember if this clot breaks off travels through where you guys remember your Anatomy travels through the inferior vena cava to the right atrium to the right ventricle from the right ventricle into the pulmonary arteries okay and then boom it gets lodged somewhere in there what happens it can lead to significant hypoxia so because of that you want to be very careful so you can also treat these for patients with pulmonary embolisms right so pulmonary embolisms obviously with these things you can do other treatments as well but pulmonary embolism is going to be you can treat this acutely with again same concept here you can treat them basically with the same things so just remember low molecular weight heparin or unfractionated heparin in this kind of situation you're more like to go with the unfractionated heparin just because of the severity and the c-series danger that pulmonary embolisms present on the patient okay now with that being said it's not just also for acute so I want to make sure I remember I put that down here it's good for acute pulmonary embolisms and acute DVTs but you can also use it for prophylaxis so don't forget that as well I'm gonna put a little side note over here that you can use it for prophylaxis okay of DVT and PE especially low dose okay so this would be good for low dose heparin okay especially if someone's had some type of surgical procedure which caused them to be bedridden right you could treat them with a low dose heparin and again this would be ideally your low molecular weight heparins because that's your sub q injections and they have a longer half-life and they have much less side effects but you got to be careful and we'll talk a little bit later about comparing the two low molecular weight heparin can be heavy on the kidneys especially if somebody has already pre-existing kidney failure or decreased glomerular filtration rates alright sweet deal we got acute DVTs acute pulmonary embolisms is the main thing that i want you to remember but you can't give low doses of it for prophylaxis of DVT and PE s what's another reason to give heparin another one guess what happens here let's say that for whatever reason if you guys don't know we talked about all the different types of causes of why someone can develop a clot inside of the actual coronary circulation all right we talked about that in our coronary artery disease video but there's multiple different reasons it's usually a thorough sporadic plaques that developed because of patients who are hypertensive and so on and so forth right but we know that if this happens it blocks blood flow to the myocardium of the heart what we can give in patients who are suffering from what's called a STEMI or even an instantly we can treat them with heparin now generally this is going to be your unfractionated heparin and again what did I tell you you're gonna do with this you're gonna give a bolus of it then after that bolus is given you're gonna do a continuous infusion through an infusion pump okay and you'll monitor the patient's PTT we'll talk about what that is later but again unfractionated heparin you're gonna give this to patients who have a STEMI and maybe are going to the cath lab to get PCI or inst Emmys and it's just their main treatment they're not high risk the instantly doesn't have to go get PCI so you're just gonna treat them with the heparin to basically prevent any types of complications from developing so again that's some thought of something really too important to remember here another thing what if someone has atrial fibrillation if they have atrial fibrillation what do we say happens here we said that the different there's all these reinsurance circuits that are firing at different times and because of these reentrant circuits are these multiple ectopic foci that are basically firing up at different points in time the atrial contraction is very very weak okay and so because of that we said virchow's triad means that if there is a stasis of blood flow what can happen you can form clots right so an atrial fibrillation you can get these clots that develop usually around the valves the mitral valve right and there's multiple different reasons why patients develop a fib but here's something I got to stress it because I don't want us to you know think that you can forget about this if someone has non valvular a fib that means that their atrial fibrillation is not due to mitral valve disease or due to a prosthetic heart valve it's some other reason maybe it's due to excess of catecholamines maybe it's due to hypoxia from some type of lung disease maybe it's due to methamphetamines man whatever it might be electrolyte disturbances it's just not due to the valves being diseased in any way shape or form you've got to remember that warfarin is the main thing that you give for patients with afib because it can treat patients who have non valvular afib as well as a fib but heparin and all these other direct factor inhibitors are mainly for non valvular a-fib okay that's important now again you're probably wondering okay well then why don't I just give them warfarin here's why you give patients heparin and if someone's having afib let's say that it's really bad they're having severe palpitations they're having chest pain they're short of breath maybe they're syncopal whatever it is and they are really struggling you bringing them into the emergency room you check the EKG strip and they're in really bad afib with like RvR rapid ventricular rate right and you try to drop their heart rate down how do you try to drop their heart rate down let's say that you try to give them medications right so you try to block the actual AV node let's say that you tried to give medications that are gonna try to slow that down what are some of these medications maybe you try to give them a beta blocker maybe you try to give them a calcium channel blocker or maybe even try to give them digoxin and just inhibit that AV node and slow down the rate so that you can allow for the ventricles to stop contracting so intensely what if that doesn't work you try to rate control them so that's the first step you do and patients with afib first step your rate control if that doesn't work the next step is to do rhythm control so how do you do rhythm control well you can do it either giving medications again things like sodium channel blockers but the more likely thing that you're gonna do because of the risks of torsades de pointes with giving things like a butyl ID is you're gonna you're gonna shock them now you're gonna do it's called cardioversion problem with that is is if I try to give somebody let's say that somebody has a fib and they already have a clot that's there okay then I go ahead and I shock them so I do cardioversion right let's draw a little lightning right so I shock the frak out of them right I give them a good shock and I reset the entire atrial circuitry and now the SA node starts firing beautifully and you go back into sinus rhythm well now the atrial contractions are gonna go back to their normal efficacy right if they go back to the normal efficacy and they start pumping really well then what could happen to that clot then it could pop off and if it pops off won't pop off then what can happen that sucker could then go into it could leave the left ventricle and go into the actual systemic circulation whenever you're giving heparin you're giving heparin to patients who failed rate control for afib had to go on to rhythm control and get what's called cardioversion and here's the thing you got to remember if they're getting cardioverted you never shock someone without doing an echo you got to do a transesophageal echocardiogram to look to see if there's a clot there because if you do shock them that sucker can break off and go to the brain so you'll heparin eyes them wait for that go calm them come back do another echo make sure that there's no clot and then you'll cardiovert them but no matter what long-term effects is you have to anticoagulate them so after you cardiovert somebody no matter what you have to anticoagulate them but if you do an echo you find a thrombus there you don't cardiovert them you anticoagulate them have them come back cardiovert them and then put them on anticoagulants for like three to six months okay so you got to remember that so now if we protect the patient from this type of situation with afib what do we protect them against downstream you protect them from these emboli breaking off and causing a cerebral infarct a renal infarct right so you're preventing the CVA you're preventing some type you're preventing renal in Forks you're preventing splenic infarcts the most dangerous one that you got to be careful of this is the most dangerous one if you don't remember any of these at least remember the CVA splenic infarcts as well as Mezen Taric ischemia which is again mainly the SMA and ischemic colitis which is mainly going to be affecting the ima or an acute arterial embolus that forms with inside of the arteries within a leg and I can lead to limb gangrene and that's the danger of this one in other words the actual tissue downstream from this occlusion can start undergoing necrosis so again big things to remember is you're protecting them from non valvular afib and all the downstream effects in STEMI stem 'is acute DVT s and p es as well as low-dose prophylaxis for DVT and PE s alright so last thing that we need to cover is the adverse drug reactions or side effects and again any contraindications will be able to fly through the contraindications really quickly and some of the ADR so there's one big one that I want us to talk about rare but I actually have had a family member suffer from this condition so we do actually want to talk about it because if it does happen you need to be able to notice and it's called a chai tea heparin-induced thrombocytopenia so we'll talk about this but we're going to kind of fly through this it's pretty simple we're talking about in all the other anticoagulant antiplatelet videos what's the risk of putting someone on an anticoagulant bleeding and again how do we notice this what are some things that we want to look for that we just don't miss look for bleeding in different surfaces or orifices so if someone's bleeding from their gingiva so if they have gingival bleeding that could be a sign oh they're on too much of this or if this share looking person is bleeding from their nostril holes right so they have anterior epistaxis that should also be a sign or if you start seeing a lot of pinpoint hemorrhages or lard pit large pinpoint hemorrhages or large bruising within the skin and again this could be petechiae this could be prepare which are just larger petechial lesions it could be ecchymosis which are very large bruising again look for any of those signs that could be in that they're bleeding a lot right what if they have blood in the urine right so you have blood in the urine hematuria that's something to watch out for as well what if they have blood in the poop right so they have hematochezia or the blood in the actual stool is dark Malena okay what if they're vomiting up blood hematemesis or what if we don't even know that and they just have iron deficiency anemia okay and again because maybe they're losing blood but it's not visible remember what I told you to do here do a fecal occult blood test that's important to do always test for that if you think that someone is actually having blood loss again you could do a CBC as well so we'll put that down there CBC just to check their MCV as well and their hemoglobin other things if someone is having heavy vaginal bleeding or menstrual periods so if you see anything like that that is important now one of the big things you got to remember is when someone is actually treated with heparin you can sometimes give them too much heparin and they can bleed too much whenever someone is given too much you want to remember the antidote and that antidote is called protamine sulfate okay protamine sulfate is the main antidote that you treat patients with who are actually you're giving too much happen and they're adversely bleeding more than you want protamine sulfate is more effective against unfractionated heparin and a little bit less effective against the low molecular weight heparin like an ox Oparin and Delta Perrin and it actually doesn't really affect the Fonda paradox if you really want to remember there is another one for fun too paradox it's it's a might work it's not as green as protamine sulfate for unfractionated and low molecular weight heparin but PCC this would be good for the Fonda paradox okay all right so I want you guys to remember these are the big big side-effects what else do we need to talk about again we said this heparin-induced thrombocytopenia pretty rare reaction but again you want to be aware of it what happens is let's say that someone let's do the easy thing let's say that they've actually received had heparin before when they have heparin for some reason their body reacts to specific things like well here's what happens right remember we have heparin heparin can actually sometimes cause these it can bind to inactivated platelets okay on platelets they have this specific molecule here called platelet factor 4 so here we have what's called platelet factor 4 sometimes what can happen is when the heparin reacts with this actual platelet through the platelet activate a platelet factor 4 so here we can put here some pepper and we'll put in combination here we'll put H this can cause this complex to become immuno genic okay so when platelet factor 4 and heparin combine on this platelet surface it can become immuno genic I actually need to write that down that's very important because that could be some type of question that you might get on an exam but it is immuno genic and what that means is is your immune system is going to respond to that so how does it do that let's say here we have some antibodies that are made by your plasma cells okay so your plasma cells make these specific types of antibodies and these RI G G antibodies these IgG antibodies will then combined and we're gonna draw this in simplicity now let's say that we draw here a platelet factor for here let me get a little bit bigger and we're just gonna draw the heparin as a red dot here this immuno genic complex this antibody will bind on to when it binds on to this two things can happen one is it can actually tag these platelets for destruction by the spleen so now draw a cute little spleen we drove green over here so let's say here we're gonna draw a cute little spleen and these are gonna get taken to the spleen so they get tagged we'll put here tagged right and then the macrophages which are inside of the spleen are actually going to break this down so then they'll get destroyed by the actual spleen another thing that can happen is is it can activate the platelets so now if I would draw a platelet here look at this platelet it is ready to cause some bad bad problems this dude is ready to start causing a lot of issues what do I mean well now it's got this tag thing here all right we got the heparin we got the platelet factor 4 this is our immunogenic complex here then we got our IgG antibody that's binding to this guess what this does this activates the platelet and now if this platelet is activated guess what starts binding to it other platelets and so guess what will results out of that if I have a bunch of platelets that start increasing binding to one another what does that mean I'm gonna form a clot so these platelets will get consumed in forming clots but they'll also get destroyed by the spleen what's the end result if they get consumed in clots as well as they're getting destroyed what's the overall result a decrease in platelets if there is a decrease in platelets what is the name for that thrombocytopenia now if you form all these clots where can they go they can they can actually go to different places in the body some of them that they can actually go to is going to be in the veins of the leg and it can form DVTs it could then travel from that DVT and go to the lungs and cause a PE it could also travel to the myocardium of the heart in cause a myocardial infarction it could also travel to the actual central nervous system and cause a CVA cerebral vascular accident as well as something that's not as common but it can't happen it's also called cerebral venous thrombosis so remember both of these cerebral venous thrombosis and cerebral vascular accident is another thing that it can cause and you don't want to forget that it also has the capability of forming clots with inside of the legs the arterial circulation and causing an acute arterial occlusion which can lead to limb gangrene okay so these are things that you come to be careful if you see how serious this can be so what can happen if you give someone heparin that's already been let's say that I want to make sure I'm very specific in because I don't want to confuse anybody if you've never received heparin and you have this reaction for the first time it takes about maybe 1 to 2 weeks before this reaction to occur because you have to produce antibodies against it but let's say that you've received heparin in the past now you're gonna have those antibodies that are gonna be made against this immuno genic complex so let's say that you received heparin two years ago you have for some reason you get a DVT you come in you got to get treated with heparin guess what can happen within a day you can actually have this response and you can develop clots all over the body and you can add these widespread clots as well as decrease in platelets this is called heparin induced thrombocytopenia where you have decrease in platelets but you have the paradoxical clotting process here so how do we diagnose this there's this very specific test that they utilize it's called the serotonin release assay this test is probably one of the coolest tests ever I just I love this test serotonin release I say this is your gold standard test and what they do is they take the person's serum which should have the antibodies right should have these IgG antibodies in it let's draw that here they take the patient's serum which should have assuming that you've been exposed to it but in the past or you've made it you take these IgG antibodies which are in the serum okay assuming that it is so this is the patient's serum you take some donor platelets okay so you take these platelets these donor platelets and you combine them you put these donor platelets in them and the donor platelets should have this playlet factor for okay and again you're also going to have heparin there what should happen then is if your platelets get activated what are those chemicals that it releases this is so cool guys remember one of the chemicals it releases when it gets activated ADP thromboxane a2 and serotonin 5-hydroxytryptamine so if these IgG antibodies are there you give them donor platelets with the pf4 and again there's going to be heparin within the solution it triggers that immuno genic complex binds to the platelet activates the platelet what should be in high concentrations in this final tube an increase in 5-hydroxytryptamine or serotonin and that would be a positive test so if there's elevated levels of serotonin that's a positive sign for heparin induced thrombocytopenia in that cool so what do you do and stop shop giving them this heparin so the treatment is really relatively simple treatment discontinue heparin and then put them on another medication which we'll talk about in another video so we'll switch to another medication which is going to be a direct factor to inhibitor and these would be things like our gotra ban and we'll talk about that in another video so you'll switch them to a direct factor to inhibitor things like our gotcha ban all right so last thing we're pretty much blow through there's contraindications it's relatively simple you don't want to give it to someone who's bleeding okay if they have uncontrollable bleeding for whatever reason they have a you know some type of you can D condition any uncontrollable bleeding now this is not something that you're gonna want to give to somebody if they just recently had a CVA why why is that important someone just happens quemic stroke can you give them heparin what can you do you can convert what's an ischemic stroke into a hemorrhagic transformation and that's a very serious thing that we don't want to have it happen okay we also don't want to give this to patients who have uncontrollable hypertension because obviously if they have uncontrolled high blood pressure what are they at risk for aortic dissections aortic aneurysms and therefore bleeding so again it's pretty simple you just want to avoid that now here's what a really important one that I don't want you guys to forget you guys want to remember this one because it is key to knowing when you use which medication if someone has now generally happens remember I told you there's unfractionated heparin and there's low molecular weight heparin don't worry about the fond of paradox these are the two main ones I want you to know the unfractionated heparin I want you to remember that it's actually nice to the kidney okay it's not really super super hardcore on the kidney the low molecular weight heparin this is bad on the kidney it can be pretty rough and really in order for this guy to really be excreted through the kidneys it needs a good glomerular filtration rate approximately you want it to be greater than thirty milliliters per minute on the creatinine clearance okay you'd like it to be but let's say that their creatinine clearance drops so someone is showing signs of renal failure let's say that they're in renal failure okay and what happens as a result of that their creatinine clearance drops and their GFR is gonna drop if it drops to anything less than thirty milliliters per minute you should not be giving them low molecular weight heparin this is no go alright so if this is the case this is a no-go you do not give low molecular weight heparin you switch to the unfractionated heparin so again that is an important thing to remember as a potential contraindication and patients who are receiving heparin if they have signs of renal failure or the GFR drops less than 30 milliliters per minute do not give low molecular weight heparin switch to the unfractionated heparin or if you want to you can just make sure that you very very carefully control their dosage okay but it's a relative contraindication in these patients alright last thing i want to mention i talked about that PTT if you guys remember PTT is called d and we're gonna mark it down here PTT is called the partial thromboplastin time and we're gonna put a little a in front of it and i'm explaining why so PTT let's write this out here is called the partial thromboplastin time it's the time it takes for the intrinsic and common pathway to occur okay so it's the time it takes for factor 12 to activate factor 11 to activate factor 9 to combine with 8 activate 10 convert prothrombin to thrombin activate the fibrinogen and turn it to fibrin and form a clot so because of that it's gonna be longer than the PT which was the prothrombin time which was the a measure of the extrinsic pathway in the common pathway right so what do we do we take the patient's plasma so let's say that this is my plasma okay we take the plasma we send it to the lab the lab then takes a specific molecule they call it the only reason that I'm mentioning this a-here is that so you don't get confused whenever you see someone they write it as PTT or a PTT they're really the same thing the only thing that you're just specifying is that if there's a in front of it you combined what's called an activator so in the lab they throw in a specific molecule I think usually they use things like silica there's a common activator and they like silica and they'll throw that in there and that's supposed to basically help to trigger the activation of factor 12 okay and that'll start this whole process so what you want to know is how long does it take for me once I add in the silica into this actual solution to activate factor 12 how long is it going to take before the blood clots to go through the intrinsic and the common pathway now normal PTT is usually usually 30 to 40 seconds that's like the average so we'll put here again we'll keep consistent aPTT the activated partial thromboplastin time is usually 30 to 40 seconds but now think about this you give someone heparin remember what happened does it affects thrombin which is a part of your common pathway it also affects factor 8 right because thrombin and it also affects factor 10 so it does have an effect on the common and the intrinsic pathway so if you give heparin so now think about this if you give heparin what's going to happen now to this whole equation process it should take a longer period of time so now the time it takes for the blood to clot it should be longer because I'm giving an anticoagulant so what we want is we want the activated partial thromboplastin time and we're gonna put here no heparin we want afterwards the activated partial thromboplastin time the activated partial thromboplastin time we want this one to be somewhere 1.5 to 2.5 times the normal range I'm going to put just in R which is this the 30 to 40 seconds and this is for heparin okay so this is with APRA okay that is the significance of this PTT all right so let's take for example here on the lower limit okay so we say that the PTT let's say that we take 30 all right that's the lower limit of this normal range we multiply it by 1.5 okay so if I multiply this by 1.5 sets 30 times 1.5 that's equal to 45 okay now I'm going to take the other example let's say I take the upper limit of the normal range 40 and I multiply that by the upper range of the with heparin so now 2.5 that's equal to a hundred here's what I want you to remember if the PTT is less than 45 what does that mean that means that I don't have enough heparin it's it's clotting relatively quickly close to the normal range without heparin we don't want that now that means I don't have enough happen and I'm more likely to clot so again if the PTT is less than 45 which is kind of like the lowest range of this port here with heparin that means there's not enough and you're more likely to clot if the PTT is greater than a hundred that means I'm outside of the normal range with heparin and now I gave too much heparin and the patient is more likely to bleed okay so we have to be able to be aware of this range okay given these numbers whenever somebody is put on heparin okay last thing I'm going to talk about here we talked about a little bit in parts of this video here is that again unfractionated heparin low molecular weight heparin I just want you guys to really know when do I give this one what's the big difference between these two unfractionated heparin low molecular weight heparin what about their administration so remember this unfractionated can be given IV but it can also be given sub Q okay low molecular weight heparin is mainly sub Q administration okay so that's one big thing the next thing that I want you to remember is halflife unfractionated heparin has a very short half-life i wouldn't say very short but it's like four times less than low molecular weight heparin so this one is actually gonna have a longer half-life and that's nice because one of the reasons why that's important is if you have a longer half-life you don't have to take it as often and that's good because this is good for outpatient types of situations next thing what about kidney function remember unfractionated heparin is nice to your kidneys it's kind of good whenever someone does have renal failure but low molecular weight heparin is kind of rough on the kidneys and if someone has less than 30 milliliters per minute it's not something that you're gonna want to give the other thing that I want you to remember is side-effects which one is more likely to cause bleeding the unfractionated heparin is more likely to cause bleeding whereas the low molecular weight heparin is less likely to cause bleeding okay now the other thing is if you really want to remember the heparin induced thrombocytopenia it's actually more common in here we'll throw that in there h i-- t is more common and unfractionated heparin administration and less common with the low molecular weight heparin use okay and the last thing that we got to mention here is that and we can we didn't talk about a ton here but what I want you to remember here is that unfractionated heparin is really the heparin that we use for monitoring the PTT go back to the reason why unfractionated heparin heparin inhibits both factors to thrombin and factor 10 so it is primarily the one that we use the a PTT to monitor the low molecular weight heparin like an ox apparent and Delta prim we don't really use the PTT if you remember why he only inhibits factor 10 right and then indirectly factor 2 so because of that because he doesn't affect thrombin we really don't use the PTT for him so we monitor factor 10 a activity okay and that's what's gonna give us you know how well this actual low molecular weight heparin is is doing in the body especially if someone has kidney failure okay so again one big thing that I want you to forget low molecular low molecular weight heparin we monitor factor ten activity unfractionated heparin which is heparin we're talking about here with the PTT that we measure with the a PTT and if you really want to remember Fonda paradox we mainly can also use factor 10a activity as well okay so that's the big things that I want you guys to know for heparin I ninja near so I hope this video made sense I really do hope that you guys did enjoy it if you guys did please smash that like button comment down in the comment section and subscribe seriously subscribe also if you guys can go down in description box we'll have links to our patreon account our Facebook or Instagram go check those out and engineers we love you and as always until next time [Music]

Channel: Ninja Nerd

Views: 84,216

Keywords: Ninja Nerd Science, Pharmacology, Heparin

Id: b4XienzkCms

Length: 58min 5sec (3485 seconds)

Published: Sun Mar 08 2020