Antiplatelet, Anticoagulant, Thrombolytic Agents

foreign what's up Ninja nerds in this video today we're going to be talking about a behemoth of topics okay we're going to talk about anti-platelets anticoagulants and thrombolytics all the blood thinning medications we're going to get into them but what I want you to do is before we actually get started in this video If it makes sense if it helps you if you really do like it please support us hit that like button comment down the comment section and then please subscribe I know I say this a lot in every video but I really mean it if you guys get a chance go down the description box below there's a link to our website on there you'll find amazing notes amazing illustrations and the reason why I encourage that is because these videos are filled pack filled with information they're time consuming there's a lot of things to go over a lot of talk and a lot of drawing I think one of the best ways is by actually following along with me I'm grabbing the notes grabbing the illustrations and then filling in some of the spots as we go through this video I think will really help you guys to understand reduce the amount of times that you have to go over something watch the video again so please check those things out I think it'll enhance your learning but nonetheless let's get started on this topic when we talk about all of these medications anti-platelets anticoagulants and thrombolytics I think that they best fit okay with their mechanism of action if we talk about what phases of hemostasis they affect now we are not going to go through all the depths of hemostasis it'll take way too long we already have a video on that in our hematology playlist go check that out if you guys want way more detail on it what I want us to understand is there's three primary phases that I want us to really think about with hemostasis and that's the platelet plug formation that kind of forms your primary hemostatic plug and then afterwards there's the coagulation Cascade and the fiber analytic mechanisms okay these are the three primary phases and why I think this is important is because the drug that we're going to talk about anti-platelet anticoagulants and thrombolytics work in these three particular phases of hemostasis so if we have the basic understanding of how those phases occur all we need to do is talk about how the anti-platelets fit into that how the anticoagulants fit into it and how the thermolytics fit into those phases okay so first stage here plywood plug formation it's not complicated right the vessels naturally your endothelial cells naturally can inactivate your platelets the way they do that is they actually release particular molecules such as nitric oxide prostacycline and what that does is it's really cool but it kind of keeps the platelets inhibited so there's a plate that's inhibited can't bind to the endothelium because it's actually going to be repelled by these particular molecules now endothelial cells become damaged blood vessel becomes damage loses the ability to release nitric oxide release process cycling now it wants to go and attach to this sub endothelial layer see this blue lining here of the blood vessel that's collagen so that's the sub endothelial lining and there's a particular protein here that we're going to zoom in on here in just a second but it's actually very well present in this sub-endothelial layer and this protein is called Bond wilderon factor and platelets they don't love that one mode one factor all right they love it and so what happens is whenever they're not being inhibited by nitric oxide they're active they love to come and bind to the actual Von wildebron factor and then they form like this plug here of where the vessel is actually injured but what's really cool is once they form this plug once they kind of this plug starts beginning to form platelets become activated and they release all these different types of molecules we'll talk about some of them but things like ADP thromboxin A2 they'll secrete things like Von Willebrand factor they'll secrete things like fibrinogen so many different molecules and so what we got to figure out is how can we utilize anti-plated agents to stop the platelets from forming that plug because it may seem like it's a it's a good thing to stop right and that's that's important whenever patients are pathologically forming clots now naturally you injure a vessel you want to be able to form a clot that's a natural physiological process but if a patient is forming a pathological clot you want to prevent that pathological clot from forming how do we do that let's take this particular process in here where the platelets are interacting with the sub endothelial layer and zoom in on it and see how this is happening so here we got two little Cube platelets now the platelets as you can see they're bound to the collagen lining so here's our collagen lining so this is all going to be the collagen of our sub endothelial layer now I told you that they're bound to specific special proteins here what are these proteins what are these cute little proteins here these proteins here are called Von wildebron Factor what are these called Von wildebron Factor these are made by platelets they're also made by injured endothelial cells so platelets can make this protein because guess why if they make it then they have something to bind onto and if endothelial cells make it it means that they're probably injured so cool thing there now not a super special important connection but I'm going to quickly mention it Von wildebron Factor does bind with platelets how well they don't just bind to the surface of the play they bind to be a little special receptor there is a protein here in red that literally kind of interacts with this and this is called the gp1b protein so there's a little GP 1B protein again I don't think it's super clinically relevant but it's just so that you understand that there is a connection between these two now the platelets they were not inactivated because of why there's no nitric oxide no process cyclin by these damage endothelial cells so then the platelets want to stick to the Von wilderman Factor via the gp1b once they bind here's what's really cool they start to become activated in a particular way once they become activated it may trigger these particular platelets to release cytokines so they have these things called granules so there's all these different types of granules that are present in the platelets and these granules contain so many different molecules but once it becomes activated it'll secrete all of these particular different molecules to surrounding platelets as kind of like an alarm system hey platelets there's a lot of things going on here get over here what are some of these molecules well some of them that it may release Here is it may release as I told you Vaughn Waldron factor to potentiate more interactions between platelets and the actual vulnerable factor with the collagen connection it also can release another protein here called fibrinogen we'll talk about how that's relevant in a second it can also release things like calcium which is involved in the coagulation Cascade but there's really two specific things that I want you to know one is it releases a very special molecule called ADP okay release a molecule called ADP now what's cool about ADP ADP adenosine diphosphate is a very interesting molecule that it likes to go and interact with this specific protein receptor on other platelets so other nearby platelets this ADP will come and bind onto this particular receptor so ADP is going to bind onto this receptor when it binds onto this receptor what it's going to do is it's going to stimulate this platelet and the way that it does this is it does it by various mechanisms but really it's just going to try to increase the intracellular calcium inside of the actual cell inside of this platelet and calcium can lead to a lot of different things that we will talk about in just a second but that's one very special mechanism so I'm going to go ahead and put like a little one here a little one like a Roman numeral one that this is one specific Target of antiplatelets okay so ADP binds onto these ADP receptors you know what helps me call these receptors we call them p2y12 receptors what are they called P2 y12 receptors p 2 y 12 receptors now I'm going to quickly tell you what this actually does when ADP is released by platelets that bound to the actual Bond multiple factor of this injured vessel it binds to these receptors increases intracellular calcium now what does that do the increase in intracellular calcium is going to activate a couple different things one is it's going to stimulate the expression of very special receptors on the actual cell membrane of the platelets what is this receptor here called this receptor here in pink is called g p 2 B 3 a receptors so these are called gp2b3a receptors or proteins now whenever the platelets actually Express this particular proteins on their surface it's a real kind of like connection imagine it being like the hands of the playlist trying to grab onto the other platelets nearby so the playlist becomes activated it releases this chemical to activate nearby playlists to grow arms and to hook onto it and catch it and then all it really does is it kind of forms like this whole like Plinko or whole accumulation of playlists that are holding on together to come to this area of where the vessel injury is the platelet plug formation now there is a particular protein that is really bridging this connection and we already talked about it right here and it's this one that the platelets are making did I tell you about this one what's this protein here called This is called fibrinogen that's called fibrinogen your platelets actually make this because they know that they're going to need it to act as the bridge between them and so look what kind of sneaks in between here my friends oh this is so cool the fibranagen the fibranogen is what allows for the plates to be able to stick with one another and really help to form that platelet plug that's one of the mechanisms of ADP the second thing is when you increase calcium it also will activate the granules to become activated so it'll stimulate these granules to become activated to fuse with the cell membrane and guess what potentiate everything that we just did in other words release more Von wildebrand factor to bind here for more platelets to stick to release more fibrinogen so that we have more kind of bridging connections between platelets release more calcium so that we have more things necessary for the coagulation Cascade and then release more ADP so that you can go and then stimulate other playlists to come nearby come to the area where the injury is become activated and then connect with them Isn't that cool so what's really interesting about this is what if I came up with a one other mechanism so there's two things so far one is calcium causes this it causes this there's one more thing oh it's cool in the cell membrane we have a very special molecule it's phospholipids right phospholipids make up most of this but what happens is you have a special enzyme here that becomes activated by calcium and this is called phospholipase A2 and what phospholipase A2 will do is it'll break down the phospholipids in the actual cell membrane and make something called arachidonic acid and then arachidonic acid will then get broken down into something called thromboxane A2 right it'll get broken down to something called thromboxane A2 now through unboxing A2 which is a really cool molecule can actually get released out of this particular platelet so we can get released out of the platelet and then it can go and do all the similar things that ADP does so in other words in order for me to do this calcium becomes active a calcium causes the activation of this particular enzyme that then activates the phospholipids to break down arachidonic acid into thromboxin A2 well I mean it breaks it out of phospholipids into arachidonic acid arachidonic acid gets broken down into thrombox in A2 and the way that thrombox82 gets formed from arachidonic acid is another special enzyme and that enzyme is called the cyclo oxygenase enzyme Cox enzyme keep your minds clear so we have the Cox enzyme which is important for being able to stimulate the actual breakdown of arachidonic acid into thromboxin A2 and then through unboxing A2 will get released and all I really want you to think about is that through unboxing A2 just so we can write it here from boxing A2 acts very similarly to ADP so thromboxin A2 acts very similarly to ADP so if you think about it for unboxing E2 if this was a little site for this one so let's say here's the throne box you need who gets released so here's the unboxing A2 gets released from a platelet and it binds on to this particular site it's going to increase the intracellular calcium if you increase the intracellular calcium you will cause the increased expression of gp2b3a proteins you'll cause the activation of the phospholipase A2 which will increase the arachidonic acid Pathway to increase throneboxin A2 and third increase the release of all of these particular different molecules that are important for platelet activation platelet aggregation platelet sticking and formation of the platelet plug Isn't that cool I think it's pretty it's thinking cool there's one more thing though so we know that with this being said here that thrombox I need to combine on to particular receptors and increase calcium we know that ADP can bind onto these p2y12 receptors and increase calcium so we know that this is a particular mechanism for them is to increase the calcium well I think what's really important is is that there's something else that actually controls this at cyclic amp so there is a molecule present inside of our actual cells here and this is called cyclic amp and what cyclic amp does is it actually is going to inhibit the increase in calcium so cyclic amp will inhibit the increase in calcium that's an important concept and so if we have a special enzyme that actually regulates cyclic amp that that enzyme may be able to increase the calcium levels because if we have increase in cyclic amp that's going to decrease the calcium levels so here's what I want you to think I actually want you to think about like this then so we know that these molecules increase calcium levels I also want you to associate that cyclic amp is a molecule that's present in these actual platelets and if we activate cyclic amp cyclic amp can work to decrease your calcium levels and so in other words you won't perform all of these functions so there's a special enzyme here and this enzyme is called the phosphodiesterase three enzyme and what this enzyme does is is it actually is going to typically break down the actual so you know phosphodastrases they break down cyclic amp so this would specifically work to inhibit cyclic amp so if I don't have cyclic amp that's increased I won't be able to decrease my calcium instead I'll have less cyclic amp and therefore a increase in calcium and so I'll still allow for this whole process to occur you're probably wondering Zach why in the world are you telling me all of these particular things I got you if I could come up with a drug to inhibit all of these red specific points here wouldn't that be pretty cool I got you so what I'm going to do is I'm going to start off with the first one that we mentioned I'm going to inhibit the p2y12 receptor and I can use a lot of different drugs to perform this function here so some of these drugs would be the most common is Clopidogrel another one is called prasugural another one is called ticagrelor and another one which is not really often used is called taclobodine but these are inhibiting what specific receptor this receptor so in ADP which is released from an activated platelet that tries to cause platelet activation plated aggregation platelet sticking forming the Plato plug it really is controlled via that receptor well what if I inhibit this particular receptor can it cause an increase in the calcium levels no won't be able to trigger the signaling pathway so I won't be able to increase calcium I won't be able to express gp2b3a proteins I won't allow for the playlist to stick with one another I won't allow for it to release through unboxing A2 which acts just like ADP to increase calcium cause these receptors to be expressed and cause cytokine release also if I inhibit increasing calcium I won't be able to release things like ADP calcium fibration bottom water Brown Factor all of these things that are important for forming the platelet plug all I got to do is block that receptor and I inhibit platelet plug formation pretty cool okay another thing is what if I inhibit the cyclooxygenase so in other words let's say that the this pillow becomes activated it does Express the gp2b3a proteins it does try to release things like ADP and all these other molecules but it tries to activate this Pathway to increase the formation of thrombox in A2 which performs similar functions what if I inhibited this enzyme I wouldn't be able to form thrombox I need to and if I don't form through unboxing A2 so in other words if I decrease the thrombox in A2 I won't be able to increase intracellular calcium and cause all these three Pathways to occur I won't allow for platelet sticking platelet activation and aggregation and then again that risk reciprocal cycle to cause platelet plug so this would be where a drug category such as your Cox so inhibiting the Cox enzyme would be very very helpful and this is one particular molecule here and this is called acetyl salicylic acid also known as aspirin sometimes we abbreviate this ASA which I'll be using a lot all right so we understand that right so so far we've inhibited two particular things we've inhibited the p2y12 receptor which inhibits the increase in intracellular calcium we inhibited the Cox enzyme which inhibited the thrombox in A2 formation which will also decrease intracellular calcium what else could I do what if I just didn't allow for the platelets to stick with one another if they can't stick with one another they really can't form a platelet plug they can't become truly activated and form a good play the plug so what if I just directly inhibit this connection here wouldn't that be pretty helpful absolutely so what I'm going to do is I'm going to hit the GP to be 3A connection and that's a really helpful thing and so there is a couple different drugs that are actually utilized in this particular step so some of these could be for example AB siximab another one could be tyrothymen and another one could be eptophibitide now with all of these particular drugs we've so far gotten to the point that we've actually covered three particular mechanisms to inhibit platelet plug formation one is block the PTY 12 receptor inhibit the Cox enzyme inhibit the gp2b3a receptor so what else is there another kind of area that I can actually specifically inhibit so I've talked about how if I inhibit ADP from binding Through The receptors that inhibits the increase in interest of the calcium if I inhibit through unboxing A2 formation that inhibits the intracellular calcium increase and that's an important concept I actually want to kind of write that down is that again if you inhibit the p2y12 receptor and you inhibit thrombox in A2 formation the overarching theme for this is that you're going to lead to a decrease in the GP 2B 3A production you're also going to lead to decreasing thrombox in A2 formation and you're also going to lead to decrease in ADP formation all of these things are important right because when we talk about this all of these are involved in what particular process here two stimulate the platelet plug because we talked about how all these mechanisms work now that's these two and then specifically so this would be the Cox enzyme right that I'm inhibiting and this would be the receptor that I'm blocking and then I could specifically block right here so if I actually also inhibit the gp2b3a protein I won't be able to form the platelet plug there's another specific process here and that's really kind of like these are all trying to you know generally when you stimulate this receptor or you increase this particular molecule they increase intracellular calcium to cause this particular process so really all of this all of these particular pathways are dependent upon an increase in nature cellular calcium remember I told you that cyclic amp decreases intracellular calcium right and that's regulated by this enzyme called phosphodasterase so phosphodastrases on so let's say that this enzyme is on it inhibits cyclic amp right it inhibits the cyclic amp and if you inhibit cyclic amp calcium levels increase okay if I inhibit this enzyme now this enzyme is off I'm going to inhibit this enzyme I can no longer inhibit cyclic amp so now cyclic amp will become stimulated if it's stimulated it will lower the intracellular calcium if I lower the intracellular calcium my friends what can I now not do I can't stimulate the granules I can't stimulate throughout the gp2b3a receptor proteins and I can't stimulate thromboxin A2 formation so all of these things will be inhibited and I won't be able to potentiate the platelet plug so this is where you can inhibit the p d e 3 enzyme and lead to activation of cyclic amp which decreases your intracellular calcium there's two particular drugs in this category and this is called die pyridamole dipyridamole and another one is called silostazal PSI loss does all now when we talk about all of these drugs I think a really really important thing to understand is that these anti-platelet agents are not breaking a clot down they're inhibiting clot formation or they're inhibiting clot propagation and I think that's a really kind of important thing to kind of enunciate here is that when you're giving these drugs when you give anti-platelets they are not going to break a clot down they're going to inhibit clot formation so that you don't form a clot within your arterial circulation and they're also going to inhibit clot propagation so that the clot doesn't get any bigger within your arterial circulation and these anti-plated agents are more particularly beneficial in the arterial circulation than they are in the venous circulation there's one last mechanism that goes along with the pde3 and enzyme and I just have to quickly mention it for completeness sake in your smooth muscle so here we have a vascular smooth muscle cell so here's going to be the blood vessel that got injured if I take a piece of the vascular smooth muscle and zoom in on it here so this is a vascular smooth muscle cell there's that enzyme this is that P let's actually keep it color coordinated here this is the enzyme called pde three p d e three this enzyme I told you works specifically in what capacity Well normally we have this enzyme here called adenylase cyclase and what it'll do is it'll take ATP convert that into cyclic amp encyclic gain P will specifically work in a specific process in vascular smooth muscle to inhibit so really what it's going to do is is when you kind of work here cyclic amp will work to try to be able to activate protein kinases in these particular smooth muscle cells and what that'll do is it'll actually lead to phosphorylation of specific processes it'll activate like protein kinases in this case it could activate like protein kinase a and what that's going to try to do is it's going to try to kind of inhibit the smooth muscle cells from actually wanting to undergo a constriction process so in other words it inhibits the contraction process so this will actually be inhibited and it won't undergo contraction or movement of the myofilaments well pde3 is going to work to specifically inhibit cyclic amp so a decreased cyclic amp it would decrease the protein kinasea you would not phosphorylate and it would promote contraction right of the actual smooth muscle cell well if I give a particular drug like a pde3 inhibitor it's going to inhibit this particular enzyme if this enzyme is inhibited it's no longer going to be able to turn this enzyme off so now this enzyme is super stimulated you increase your cyclic amp you increase your protein kinasea and you increase the inhibition of the vascular smooth muscle cell from Contracting what kind of process will that lead to that'll lead to a relaxation of the smooth muscle and then a Vaso dilation effect so that's an important concept that you only see with this drug category here the pd3 inhibitor that it has anti-platelet function and vasodilatory function which could be beneficial in things like pad we'll talk about that later okay my friends so at this point we're trying to give drugs that are going to inhibit the platelet plug and that is going to be your anti-platelets we talked about how they would do that we inhibit the p2y12 receptor which ADP binds to we inhibit the Cox enzyme which inhibits the thrombox in A2 formation we inhibit the connection between the playlist that allows for them to stick and form the platelet plug be inhibiting the gp2b3a proteins we can inhibit the pde3 which helps to regulate cyclic amp if you inhibit it now the cyclic amp is on because it's normally supposed to inhibit it but you're inhibiting that enzyme so now it's on and it decreases intracellular calcium which doesn't allow for platelet plug formation and then when we talk about this it's important to remember that all of these anti-platelets are working to specifically stop clot formation or inhibit clot propagation they do not break down clots and again one more additional kind of fact here is that we have found that anti-platelets anti-platelets are going to be more beneficial at inhibiting arterial and again we'll talk about this a little bit more but arterial thrombo emboli okay all right my friends let's now move on to the next category here which is going to be the anticoagulants anticoagulants is the next component and really what they're working to do is inhibit the coagulation Cascade so let's kind of pick up right so naturally we said that the vessels they're naturally of an anti-throne body function there's many more than what I've mentioned here but obviously nitric oxide is one prostacyclin is another there's another molecule that's expressed called antithrombin 3 which we will get into a little bit later but really when we talk about this nitric oxide and process cycling is trying to inhibit the platelets antithrombin 3 is trying to inhibit things like Factor two like thrombin and another one which we'll talk about Factor 10. but either way these are trying to inhibit the coagulation Cascade so they're trying to prevent us from forming clots when we don't want to in other words pathological clots so we have antithrombotic mechanisms but the blood vessel becomes injured can't release nitric oxide can't release prostocycline Bond water Brown factors exposed play let's say um don't mind if I do and it binds and when it binds it binds while motorbox Factor via the gp1b let's see if you guys remember becomes activated releases things like ADP and when it releases ADP it binds to the p2y12 receptor increase interest of the calcium increase the expression of what protein for them to stick together GP 2b3a causes an increase in the release of more ADP plus it activates the interest of the pathway to increase through unboxing A2 which increases the same thing as ADP and then on top of that we also talked about how the pde3 enzyme is also involved in this process again to kind of work specifically to inhibit that from increasing the interest of the calcium so we talked about all these particular mechanisms okay the pleadal plug has been formed we talked about how anti-platelets will work to inhibit that once we inhibit the p2i12 receptor one to inhibit the Cox enzyme one to inhibit the gp2b3a proteins and one to inhibit the pde3 enzyme the next thing here is once the platelets have formed the platelet plug they develop a kind of negatively charged surface or an activated surface if you will so what I'm going to do is I'm going to kind of like put these negative charges there because now the platelets are activated once they are activated this forms a surface for which the coagulation proteins love and so this can activate all of these different types of coagulation proteins what I'm going to do is I'm just going to put coagulation proteins and what these coagulation proteins are going to do is they're going to go through this whole vicious cycle that will go through there's so many different arrows that are involved here all this different concept here but everything that it leads to is it leads to the formation of something called the fibrin mesh the ultimate goal is is to make something called fibrin and fibrin is this kind of like mesh-like protein that allows for platelets to be nice and cozy and stuck together and stable and it really helps to stabilize the clot really help to increase the size of the clot and stabilization of the clot so what I got to do is is I got to come up with ways that I can inhibit some of these coagulation proteins somewhere in this madness of mix to kind of inhibit the formation of fibrin because if I don't form fiber and I won't form the fiber mesh I won't kind of form this fiber and coating that stabilizes the clot increases the size of the clot all of those things so now let's get into that all right so the first concept here is we have two different Pathways I don't want this to be too intense guys let's not make it intense let's make it somewhat simple we have two Pathways one pathway we'll highlight here so we're going to have something called the extrinsic pathway and I'm not going to go through this in Crazy depth I just really kind of want to highlight more of the common Pathway to be honest with you but there's two Pathways one is called the intrinsic pathway and the other one is called the extrinsic pathway the intrinsic pathway is from the platelets so the platelets this is usually secondary to the activated platelets the extrinsic pathway is due to vessel injury so it's the actual tissue of the vessel wall that is responsible for this so the activity of platelets will activate this pathway and the vessel wall That's injured will activate this pathway okay when we activate the platelets there's so many different proteins my friends I'm going to make this very straightforward the first one is Factor 12. Factor 12 will be activated by the platelets so it'll stimulate this Factor 12. then Factor 12 will activate Factor 11. and then Factor 11 will activate something called Factor 9. and then Factor 9 will complex with another molecule called Factor 8. and when these two combine they will converge into something that we'll talk about later called the common pathway but this is your intrinsic pathway your intrinsic pathway starts with Factor 12 which is activated by platelets then Factor 11 then Factor 9 complex with factor 8 and then moves into something called the common pathway the extrinsic pathway starts off with the tissues releasing something called tissue Factor okay so tissue Factor the tissue factors also sometimes referred to as factor three factor three will then activate something called Factor seven and then you have this complex of factor three and Factor seven a that then will converge into this next specific part of the pathway okay and what this will do is there's a special protein here called Factor 10. when these converge onto this particular pathway here what they do is they help to take and convert Factor 10 into the activated form they activate Factor 10. now Factor 10 is the interesting thing because if you notice a concept here is that the extrinsic pathway and the intrinsic pathway all converge onto this common part here so this is where we get into this next thing which is from Factor 10 down we get into something called the common pathway so what I'm going to kind of do here is I'm going to write it about right here generally where we're starting now is we are at the common pathway so this is basically where the intrinsic and extrinsic kind of converge to stimulate the activation of factor 10. Factor 10 when activated will then activate something else okay so there's another molecular called prothrombin and prothrombin will be converted into something called thrombin and then thrombin will activate two particular proteins one is called fibrinogen and what it'll do is it'll convert this into something called fibrin and it'll also activate another protein called Factor 13. and Factor 13 when combined with fibrin will form something called the fibrin mesh work and that's all that kind of like orange proteins that I kind of mentioned to you before that really kind of come into play here and stick on to the play Let's Help the playlist really really stick together so if you remember all the playlists were here this is really helping to stabilize that clot increase the size of the clot really kind of form that stickiness of the clot really important kind of process here so if you see here this is really kind of an in pathway of forming this with a couple specific points one here is the common pathway and the other one is this bad boy right here so this is a really important protein right here Factor 10 and another really important one is thrombin okay so let's actually highlight this one so this is one particular protein which is really important this is a second protein which is very very important there's another one you know we have a lot of these factors that are kind of mixed within this process some are made by the liver some are made by platelets some are made by endothelial cells there's all these different proteins but the liver ones is really really important to the coagulation Cascade in the liver the liver is responsible for making special types of proteins right it makes coagulation proteins especially factors too Factor seven and this is an important one I kind of want to put like a little asterisk next to this one here that's one of the ones that we specifically talked about was in the extrinsic pathway it also makes other factors such as factor nine factors 10 protein C and protein s now all of these so factors 2 7 9 and 10 are pro coagulants they want to induce clots protein C and protein s are anticoagulants they want to actually help to prevent clot formation we'll talk about their relevance later in adverse effects but these proteins when they're made by the liver they need to be functional and the only way that they're functional is by the activation by a special enzyme there's a special enzyme called gamma glutamyl transferase and it will activate or I'd say convert these proteins into their functional forms if they are not in these functional forms they won't be able to perform their true actions and the way that gamma glutamyl transferase does this is it actually has to be in some way worked upon okay so what happens is is there's a special type of enzyme if you will um and it's working on this pathway here so there's what's called vitamin K and there is the oxidized form and then there is Vitamin K the reduced form now what happens is vitamin K in the reduced form will give away electrons onto this gamma glutamount transferase and when it does that in this step it activates gamma glutamine transfer so we need Vitamin K to be in this reduced form to activate or be a cofactor so it's a cofactor into this gamma glutamal transferase which will activate these particular proteins such as factors 2 7 9 10 C and S so this is this particular step now in order for me to be able to continue this this has to be a cycle so I have to convert vitamin K from the oxidized back to the reduced and then continue this particular cycle here so in other words Vitamin K is very crucial so how do I keep getting vitamin K to be in the reduced form so that it can donate electrons to gamma glutamal transferase keep it activated so it can make my proteins functional and then when it goes to the oxidized go back to the reduced form great question there's an enzyme here called vitamin k epoxide reductase and this enzyme will stimulate this particular step to go from the oxidized to the reduced form if this enzyme is present it'll keep the vitamin K reduced it'll keep the ggt activated it'll keep it to stimulate these functional proteins such as factors 2 7 9 10 that can be utilized in the coagulation Cascades that's very important my friends so now the question that you prior coming to is okay Zach I know the coagulation Cascade now how in the world is this actually important this is the third step the third point in the coagulation Cascade that we're going to Target okay so in other words I want to Target Factor 10. in other words if I inhibit Factor so if I use this as my first Target this is my first Target I'm going to inhibit Factor 10. if I inhibit Factor 10 I won't activate thrombin I won't activate fibrinogen to fibrin I won't have the fiber and mesh because my goal is to really kind of prevent the fiber and mesh from forming that's the end goal so one way I can do that is I can inhibit Factor 10. hmm how am I gonna do that so if I inhibit Factor 10 I can do it a couple different ways I can do it directly or I can do it indirectly so let's say that I write these two dataways down so one way that I can have a factor 10 is I can do it indirectly so I'm going to indirectly inhibit Factor 10. how do I do that how in the world can I do that great question so there's a special molecule that I mentioned a little bit ago over here called antithrombin 3. anti-thrombin 3. if you guys remember Works to do something very special it inhibits factors 10 and it inhibits thrombin so antithrombin 3 can inhibit Factor 10 and it can inhibit thrombin which is also known as Factor two just so you know thrombin is also known as that's actually pretty cool I didn't mean to have the second Roman numeral there was no pun intended there but just so you know thrombin is Factor two okay it is Factor two so if I were to give a drug that could really work to increase antithrombin 3 or activate antithrombin 3 it'll inhibit Factor 10 and then some degree inhibit thrombin that's pretty cool I really want to inhibit just Factor 10 but I can do this indirectly how do I do that there's a couple different drugs okay so one of these is called they're basically all going to be Heparin they're all going to be Heparin because Heparin will help to be able to stimulate anti-thrombin 3 and that will help to inhibit these particular factors now there's three particular types of Heparin one is there's unfractionated Heparin unfractionated Heparin this unfractionated Heparin what I really want you to know is is when you look at the structure of this son of a gun it's got kind of like a sugar molecules like a sugar moiety and then off of the edge of it it's got this thing called a glycosaminoglycan so it's got these two things they've got like a pentasaccharide it's got a glycosaminoglycam it's glycosaminoglycan is super super long so when it activates antithrombin 3 it works in a way to loop around where this antithrombin 3 now has the capacity to inhibit both of these factors so when you give unfractionated Heparin I think a super important point to remember here is that that will actually inhibit factors 10 as equal as it would inhibit thrombin so it's going to inhibit both of these so you're going to get an inhibition of both factors 10 and factors 2 equally due to Y due to an increased glycosaminoglycan the next molecule here is going to be called Low molecular weight heparin now low molecular weight Heparin similarly has again this kind of like pentasaccharide structure and it has a glycosaminoglycan but it's a lot a lot smaller so it's not as long so it does work to inhibit anti-stimulate antithrombin 3 which inhibits factors 10 and 2 but because of its tiny little glycosaminoglycan it can only inhibit factors 10 much more than it can inhibit throbbing and that's an important point to remember it's primarily Factor 10 inhibition with a very very little degree of thrombin inhibition that's pretty cool right now there is one more type of Heparin it's like a synthetic type this is called Fonda paranox Fonda paranox and this one is again has no glycosaminoglycan so it only has like the little baby pentasaccharide kind of structure with no glycosaminoglycan so there's no chance in this world there's no glycosaminoglycan so there's no ability to even inhibit like thrombin whatsoever so because of that this one only activates antithrombin 3 which inhibits only Factor 10 okay so so far we've inhibited Factor 10 we did it indirectly by increasing antithrombin three we did it three particular drugs Heparin low molecular weight I'm sorry unfractionated Heparin low molecular weight Heparin and Fonda paranox unfractioned Heparin has a long gag low molecular weight weapon has a small gag Fonda paranox has no gag the longer the gag is the more likely you're in to inhibit both thrombin and Factor 10. so since I'm fraction open is a long one it can inhibit both equally since Loma liquid radar is a small one it can only primarily inhibit Factor 10 less inhibition of factor 2 or thrombin and then since the final paranax says no poor little gag it can only inhibit Factor 10 and not thrombin okay another thing I can do here is I can directly I can directly inhibit Factor 10. so what if I want to directly inhibit Factor 10. so this is where I can have a protein that can literally just bind onto Factor 10 and render it ineffective that's pretty cool so this is what's called your direct oral direct acting oral anticoagulants but these are going to be these are usually your oral agents these are usually oral agents and I love these ones because their names are super cool so we actually call these doe ax okay this is a pixaband look at the name look at the name my friends River rocksaband a doxa ban do you notice something really cool about this that I love 10A is in there they directly inhibit Factor 10. and these are going to be a pixaban riveroxaban a doxa band these are the oral agents whereas Heparin low molecular weight Heparin Fonda paranox these are primarily via like IV or subcutaneous types of injections this is an oral agent that you can take outpatient you'll have to like inject yourself with that's really cool so if I want to inhibit Factor 10 I can do this in two particular ways I can do it indirectly via Heparin or I can do it directly via a Pixelmon riverox banded oxiban and if I do it indirectly it's because I'm utilizing anti-thram and three I'm stimulating this particular protein to inhibit these two factors unfractionated 10-2 low molecular weight 10 way more than two and then fond of paradox primarily only 10. and these only inhibit Factor 10 directly okay okay what if I inhibit thrombin is there any way I can do it indirectly thank goodness for the love of goodness there is not one that we can do indirectly thank the Lord but we can't do it directly so if I wanted to inhibit thrombin I can do this directly and that's the primary way so the primary way that we're going to do this is directly and so that means I have to have some special drug that can actually inhibit thrombin so directly and again the cool thing about these drug categories is they are oral okay there is an oral I actually should be very careful there's oral and there's IV versions of this okay so with the direct ones okay they're going to again if we think about this we think about kind of these drugs here they're specifically working via antithrombin 3 if there's all these heparins to inhibit Factor 10 or these ones directly to inhibit Factor 10. you get less 10A less thrombin less fibrinogen to less vibrin and less of the fibrin mesh if we inhibit thrombin directly we get less thrombin activation less fibrin less of the fibrin mesh what are the drugs in this category for the oral ones and then the IV ones so the oral one is going to be something called the bigotran so dabigatran this is the PO version the IV versions are going to be something called our gatraband our gatroban and another one is called bivalarudin by Valor Rudin these are the IV version and really their name to fame which we'll talk about a little bit later is in something called heparin-induced thrombocytopenia okay my friends so at this point we've covered ways that we can inhibit these two particular processes one is inhibiting Factor 10. one is inhibiting thrombin what I think was the third mechanism inhibiting the vitamin K epoxide reductase oh if I inhibit the vitamin K epoxy reductase we actually call this categories we call this vitamin K antagonists vitamin K antagonist because we're inhibiting the vitamin K epoxide reductase if we inhibit the vitamin K epoxy reductase we don't reduce the vitamin K we don't have the vitamin K in the reduced form to activate the ggt the ggt is inhibited if the ggt is inhibited it cannot make functional clotting proteins if these are not functional clotting proteins such as Factor 7 and 10 you won't be able to allow for them to activate Factor 10 and then lead to thrombin activation fiber in a fiberin mesh Isn't that cool so the primary drug in this particular category my friends is called Warfarin this is called Warframe okay my friends so at this point we have covered all the ways that we can stop the coagulation Cascade because if I give anticoagulants I'm just going to put here a c what are they doing they're working to inhibit the fiber and mesh if I inhibit the fiber and mesh I inhibit what do I break down the clot for me I don't break down clots that's super critical to remember you do not break down clots you decrease the fiber and mesh and if you decrease the fiber and mesh that gives you two kind of like processes that occur here let's actually make some room so we can write that there's two primary things that come as a benefit to that one is you decrease clot formation and second you decrease clot propagation you do not break down clots and the clots that it's primarily working on is both Venus and arterial thromboemboli all right my friends okay so at this point we've covered anti-platelets we've covered anticoagulants we got one more phase that's thrombolytics let's hit it all right my friends fibrinolysis so at this point now we're kind of the third phase is where thrombolytics comes into play I think it really kind of makes sense when you hit these back to back it's obviously going to be a behemoth of a video and I really am sorry that it's so long I just think that it's going to be helpful as one kind of inclusive video to really help your understanding and knowledge but anyway we talk about it vessel gets injured so again we talked about how naturally we release things like nitric oxide we release things like process cyclin we have things like anti-thrombin three and again we talk about how these are like your natural kind of like anti-platelet mechanisms which is specifically this one it's inhibiting platelets we talked about how antithrombin 3 is going to inhibit things like factors 10 and thrombin and there's other molecules out there we didn't talk about it we briefly mentioned it but you also have things like protein C and protein s and these are also inhibiting other particular like proclaims so you have natural kind of like antithrombotic mechanisms but let's say that again you have a vessel injury platelets stick to the bottom of the brown Factor they release things like ADP through unboxing A2 right they also increase the expression of things called gp2b3a proteins which allows for the platelets to stick with one another we have drugs that inhibit that process we have the PTY 12 receptor blockers we have the Cox enzyme inhibitor we have the gp2b3a protein receptor blockers and we have the pde3 inhibitors then we had the coagulation Cascade that occurred and the coagulation Cascade when it led to the formation of the fibrin mesh which helps to kind of really stabilize the clot increase clot formation increase clot propagation and really kind of allow for the platelets to stick with one another really form a stable forming clot and that was the fiber mesh and that was carried out by the intrinsic and extrinsic pathway and some of the clotting proteins from the liver and we talked about how we had drugs that could block specific factors in the coagulation Cascade Factor 10 Inhibitors whether it be indirect such as the hyperinfia antithromin 3 or direct such as the river rock Savannah pics of anadoxavan then we said we have ones that we can inhibit thrombin directly or factor two and we said that that would be the bigotran or gatraband by valaruden and then we had the other ones that we could inhibit the vitamin K epoxy redox Ace so it was an activate ggt doesn't make functional proteins like 2 7 9 10 CNS and so they can't be utilized to make fiber and mesh and that would have been Warfarin so we talked about all these different drugs along the way well now we move into fibrinolysis so you know there's kind of a balance when you form a clot you want to have the fiber and mesh and then you have one have something called fibrinolysis right because it's a natural type of process and so we have another kind of like anti I don't know clot mechanism if you will and it's really interesting so I'm going to zoom in on that anti-clot mechanism so basically what it would do is it would take you're going to have like some special type of process here where it'll break down the fibrin and the connection between the platelets and so essentially you would kind of dissolve the clot in a way so what you would kind of see here is you would see kind of a dissolution of the clot an actual true breakdown of the clot how does that happen so we have a molecule here called plasminogen there's a molecule here called plasminogen and plasminogen is naturally a very interesting enzyme that it can be converted into something called plasmin so it can be converted into something called plasmin and plasmin is interesting in this in the concept that it can actually break down two particular molecules so remember I told you that there was a molecule called fibrinogen and fibrinogen is you know generally utilized to synthesize something called fibrin so we utilize this to make something called fibrin well when plasminogen is converted into plasmin it can break down fibrinogen and break it down into something called like fibrinogen degradation products and it can break down fibrin into fibrin degradation products and it can even break some of this back down into fibrinogen so this is kind of what you get here when you have plasma so plasmid is really helping to break down the fibrinogen and the fibrin and break them in down into these fibrin degradation products so that you can do what will essentially dissolve the clot so the ultimate concept here is when you're giving these particular drugs that works via this pathway what you're seeing with kind of this fiber analytic pathway is that fibrinolysis leads to a decrease in the fibrin formation and a decrease in the fibrinogen this leads to a decrease in the clot size so you're going to actually break down the clot and this decreases the what is fiber engine used for this is what's really cool and I actually never knew this until recently when you think about why it actually breaks down the clot well we can break down the fiber and mesh but how do we actually kind of break up the platelets this is to a smaller degree so if you really look at this kind of this process here this is the more potent effect here for the fiber and breakdown but there is a small fibrinogen breakdown as well fibrinogen is that protein that was connecting between platelets and forming the platelet plug the actual activation the connection the arm holding between the platelets and so this was actually utilized the fibrinogen so the fibrinogen was kind of Incorporated into this connection here so it helped to be able to kind of Inc stimulate the platelet plug if you will and so if we break down fibrinogen we don't have as much fibrinogen to allow for the playlist to stick with one another and so it actually can cause platelet dissolution or platelet kind of separation and so it can actually decrease the platelets platelet connection or the plug if you will and I think that's really cool about this is that in comparison to anti-platelets and into anticoagulants those potentially help to stop clot formation prevent clot propagation this actually breaks down clots so when you think about this fibrinolysis and the true concept of the name here is that when you think about this concept here where you're actually decreasing the clot formation or you're decreasing the clot actually like stabilization and you're decreasing the platelet plug this is truly essentially breaking the clot up breaks clots are clot busting that is extremely kind of critical to understand so I think what really comes into play here is if I really wanted to break down clots I want to enhance I want to increase my fibranolytic pathway so that I can break down clots and break down the platelet connection and really help to dissolve the clot and pathological situations so that leads to me to the question here which is how in the world is this plasminogen de plasma formation occurring this is occurring via something called tissue plasminogen activator so tissue plasma engine activator will stimulate plasminogen into plasmin if I increase plasma formation I increase the breakdown of fibrinogen so I'm actually going to continue to increase the breakdown of fibrinogen decreasing fiberinogen and I'm going to decrease my fibrin by breaking that down as well and I'll lead to the dissolution of the clot so I need drugs that are going to either stimulate TPA or act like TPA how do I do that that's where we get into these drugs which are going to basically kind of increase your t p a and so there's a lot of drugs that actually act like tissue plasma engine activator the most commonly utilized one here is going to be something called altaplace so altar place there's another one which is kind of like recombinant tpas and this would be things like read a place and connect a place there's other ones which are kind of like weirdly synthesized so you have something called like eurokinase and there's other ones like streptokinase as well so there's another one here called streptokinase I'd say out of all of these the most commonly utilized one here so these are called these are your recombinant tpas this is actually going to be like true TPA this is like true TPA and this is going to be the most commonly utilized ones these are kind of like weird molecules which I would actually be very very careful with ever utilizing but I think the concept that I want you guys to think about here is with the three phases of hemostasis we have play the plug we get antiliters for that coagulation keskey we give anticoagulants for that fibrinolysis we give thrombolytics for that phase and so now we understand here that if we do enhance the fiber analysis process in other words we increase TPA so we activate this enzyme or we increase this enzyme or we increase this enzyme we're going to allow for an increase in the plasmid a decrease in the fiber engine so we have less ability to be able to so we have less fibrinogen we have less of the plate of the plug and we'll have more of these fiber degradation products if we decrease fiber and we don't have any kind of fiber and present to allow for the formation and stabilization of the clot so we'll increase these fiber degradation products and again will actually help to decrease the amount of clot present decrease the plate of the plug and will help to enhance the breaking down or dissolution of the clots isn't that a cool concept I think it is but that's really what I want you guys to obtain out of all of these mechanisms of action related to the physiology now this is a lot so what I want to do is I want to quickly test your knowledge and just hit a couple big points which one blocks this which one blocks this which one stimulates this and see if you guys can remember and then we'll go on to indications of why we utilize these drugs all right my friends so real quick if we're trying to stop or inhibit or decrease the platelet plug we had a lot of different drugs that we kind of mentioned kind of within this physiological process we could inhibit the p2y12 receptor this was the Clopidogrel the pursue girl the tachler the diclopidine this was inhibiting the plate of the plug all of these things are going to be working to decrease intracellular calcium decreasing the expression of gb2b3a proteins decrease the release of other molecules such as ADP and water Brown Factor all of those Concepts we also had another way that we could do this which is inhibiting special enzymes that synthesize through unboxing A2 this was via the arachidonic acid pathway so we take arachidonic acid and we utilize this via the Cox enzyme to synthesize this protein if we utilize a special kind of like a drug to inhibit the cycle oxygenase enzyme if we inhibit the cycle oxygenase enzyme then what will we do we'll decrease the thrombox in E2 and we won't allow for the stimulation of the platelet plug what if we gave drugs that inhibited the GP 2B 3A connection so now you can't allow for this connection to occur so the players won't be able to stick with one another and truly form a plate of plug and therefore you will inhibit the formation of a plate of the plug and then lastly we said that we can inhibit this special enzyme that also is important for regulating calcium levels and this was the pde3 Inhibitors as well so we could do these to inhibit these special enzymes they're naturally supposed to do what turn off the cyclic amp if they can't turn off the cyclic amp cyclic amp will do what to the calcium levels plummet them you can express the gp2 b3a proteins you can't release thrombox in A2 and you can't release ADP to trigger this whole process that's the drugs in this category next thing is if we wanted to use drugs to specifically inhibit what specific enzyme in this process that makes functional Factor 2 7 9 10 CNS we have to inhibit this enzyme what's this enzyme here vitamin K epoxy reductase which drug does this one Warfarin if we want to increase the production of antithrombin 3 to inhibit factors 10 and anti-throw I'm sorry thrombin they're these were the Heparin molecules and so there was the different types of Heparin unfractionated does which ones this and this one low molecular weight does this one not as much as this one Fonda paranox does primarily this one okay so again unfactionated Heparin inhibits both Loma liquid Heparin primarily 10 a little bit of thrombin and then find the paranox primarily 10. if I also wanted to directly inhibit Factor 10 I can do that which way what's the drugs again addoxaban a pixaban riveroxaban if I wanted to inhibit thrombin directly I could do it po to bigotran or IV our gatraband by valaruden man we're good and then lastly if I wanted to cause fibrinolysis to be enhanced I would want to activate this particular enzyme to increase the presence of this enzyme to increase plasminogen into plasmin and plasmin to break down fibrinogen and to break down fibrin so that I don't form a stable clot but also if I break down fiber and I can't have fiber and holding the plates together and if I break down fibrinogen I can't keep the platelets connected so the clot will dissolve anti-platelets anticoagulants decrease clot formation clot propagation thrombolytics break down and dissolve a clot okay my friends let's go into indications all right my friend so now we're going to talk about why do we use anti-platelets anticoagulants or thrombolytics so I think the reason why it's nice to kind of combine all of these together is that sometimes all three of these maybe two of the drug categories may be utilized in one particular disease so let's see how they're utilizing again I think it's really important to not forget guys anticoagulants anti-platelets are not busting up a clot they're inhibiting clot formation they're inhibiting clot propagation particularly anti-plates more in the arterial circulation whereas anticoagulants more in the Venus but also in the arterial circulation as well whereas thrombolytics they're actually breaking down a clot an acute clot all right first one will be some neurological indications for some of these drug categories well the first one that I want you guys to think about is acute ischemic stroke so if a patient develops an acute ischemic stroke of any particular etiology in general what we want to think about is what is their kind of last known well right so we're not going to go crazy down this pathophysiology but if a patient is acute ischemic stroke there is a clot forming there and this is actually leading to decreased oxygen delivery to the brain If there is decreased oxygen delivery to the actual brain this is going to lead to ischemia and subsequently infarcts of the brain tissue and so we don't want that and so it's important to establish the time frame when was the last known well if this is between three and like four and a half hours this is a time where the clot is relatively fresh and increasing fibrinolysis is the best case scenario here and so as long as they do not have any particular contraindications which we'll talk about a little bit later this would be an indication for thromboletics thrombo lytics so examples is TPA okay that would be one particular indication there so I want you to think about that the patient comes in with an acute ischemic stroke within that time frame you should give them TPA now other situations such as anticoagulants anti-platelets those could potentially be utilized but again they're more for the prevention of a lot of the atherosclerotic cardiovascular diseases so what we could do is if a patient has like a plaque within their vessel wall and you want to prevent further clot formation of propagation within that actual vessel we could consider adding on afterwards anti-platelets so usually acutely and I can't kind of stress this enough acutely we're going to be giving thrombolytics but in more of kind of the afterwards situation so and what I mean is kind of reducing the risk of atherosclerotic cardiovascular disease atherosclerotic cardiovascular disease we could add on something such as aspirin so I remember I told you that's acetous salicylic acid plus or minus a p2y12 receptor inhibitor such as Clopidogrel oftentimes this is what we would continue for the patient to reduce their risk of further kind of like plaque formation so in other words if they have a vessel plaque within their arterial system like the middle cerebral artery and they rupture that plaque they're at risk of forming a platelet plug on top of that if I can prevent that Plato plug from forming on top of the plaque I may reduce the risk of developing another acute ischemic stroke so this is more of a kind of a preventative measure so this is usually going to be more of a chronic type of utilization okay to for preventing again reducing the risk of atherosclerotic cardiovascular disease to reduce the event of another Tia or another CVA okay next indication here is if someone has a clot but it's not in the arterial circulation it's in the actual venous circulation of the brain so we call this a cerebral Venus sinus thrombosis so this is basically a DVT of the brain is essentially what it is so remember I told you anti-platelets aren't really good for Venus thromboembolize so get them out of there anticoagulants that's actually perfect because they're for venous and arterial TPA I wouldn't say that that's a true indication in this particular scenario anticoagulants are actually going to be your best bet so that leads into the question is okay which one do I pick right so oftentimes we start with a Heparin infusion or or some type of Heparin as the initial therapy so this is usually going to be the initial therapy that we'll start off with and this could be unfractionated Heparin versus low molecular weight Heparin it really kind of depends now after you've done that then what you do is you switch them over to one of the either the the 10A and the 10 inhibitor so the direct tenant a Inhibitors or the thrombin Inhibitors or Warfarin and so from there it's a transition so after you do a Heparin initially then you transition into the following so you could do a 10A inhibitor so we usually just call these doe ax so this is going to be your 10 inhibit 10A Inhibitors and this also could be your thrombin Inhibitors so in other words this could be a pixaband a doxa band riveroxaban uh the bigotran or you could do or you could do warfarin so this is generally how we'll do it so we'll start the patient off when they have they find this clot within the venous circulation we'll start them off on Heparin one of the two sometimes if they have cancer low molecular weight Heparin maybe a little bit more Superior and then afterwards we'll transition them into one of these for long-term management okay generally like Warfarin if you're kind of looking at preferences there's a lot of different reasons of why we would pick one over the other but oftentimes maybe working requires more monitoring higher bleeding risk but it may be more beneficial if the patient has anti-phospholipid syndrome so that may be something to remember so better in anti-phospholipid syndrome in comparison to doax nonetheless it's the same concept you're using anticoagulation Heparin initially because it's easy to Monitor and then transitioning them over to a regular anticoagulant that they can take at home orally Warfarin or any of the doax whether it be 10A or 2A inhibitors okay we've talked about the neurological events of why we would use these we should understand why we would use this one okay now let's move into the next situation which is cardiac events what will be indications of you know particular cardiac etiologies and which agents would we choose all right my friend so now we talk about cardiac events so a patient has a cuteschemic stroke they come in thrombolytics are best because you got to bust open that clot you don't want them to have a time period where they're not getting blood to their brain they'll develop large infarctions so thrombolytics acutely chronically long term as you're going to try to continue to reduce the risk of plot you know clot propagation clot formation on top of a pre-existing plaque especially if they have a lot of atherosclerosis in their cerebral vessels if you give them aspirin plus or minus a P2 wealth p2y12 receptor blocker that will again help to potentially reduce the risk of forming a clot on top of that plaque and again increasing the risk of them developing a Tia or a stroke now reducing the risk of them developing into air stroke sweep of uh venous sinus thrombosis on the other hand that's a venous claw thought those can cause Strokes or bleeds it's important to remember that they will not respond to anti-platelets and thrombolytics is very risky with these patient populations so because of that it's best to do anticoagulants to help to prevent further claw propagation further clot formation and allow for the clot to dissolve and break down over time okay won't happen acutely once you start the anticoagulants but Heparin transition them over to a Doak or warfarin all right cardiac events so the first one that I want you to remember that's extremely important is acute coronary syndrome so this includes your unstable angina this includes your end stemi this includes your stemi patients patient comes in with any of these features of acute coronary syndrome oftentimes we should think about okay it's an arterial clot anti-platelets right yes so what we'll start off with first is we'll start with adding aspirin so we'll do both anti-platelets believe it or not both of these are going to be very very beneficial so the first thing that we'll do is We'll add on aspirin and we'll add on a p2y12 receptor blocker okay so this is going to be the anti-platelets that we'll give right away when the patient comes in through the door and they have an acute coronary syndrome the second thing that we'll do here is if there is the plans for the patient to actually go to um specifically get a percutaneous intervention in other words they're going to go in they're going to put a catheter through the coronary vessels they're going to look at them and they're going to stint or kind of balloon open the vessel and place a stent if that is the case you can consider another antiplatelet agent but usually in very very high risk patients so this would be first situation right when the patient comes in through the door second thing to add on is it's a plus or minus let's actually make this a plus or minus so plus or minus is going to be a GP 2B 3A inhibitor this is only prior to PCI and this is let's actually write this as kind of like a little thing underneath it very high risk patients very very high risk patients in other words patients greater than 75 they have diabetes they have left ventricular dysfunction they have massively increased troponin levels these are things to consider in that patient population just got to be very careful because now they have an increased risk of bleeding if you add this drug on all right so this is gonna be the first one out on aspirin add on a p2y12 receptor blocker usually a load then you can consider this one if the patient is extremely high risk and they're getting ready to go to PCI another thing that you add on here and this is what's interesting right it seems like there's a lot but it this is what it would be best here so then you'll add on another drug which is going to be if they're going to PCI will add on a anticoagulant so this is where you prefer Heparin okay Heparin is usually going to be the preferred so unfractionated Heparin is actually going to be the easiest to titrate you can actually monitor the levels so usually unfractionated Heparin is going to be the preferred agent in this situation and again this is going to be prior to PCI and then during PCI so prior and during PCI so this is usually for those patients who are going to get a PCI okay so we'll start off with aspirin and ap2y12 receptor blocker plus or minus a gp2b3a inhibitor if the patient's high risk and then we'll add on an anticoagulant like Heparin for PCI now after they go in they actually kind of like stent open the vessel place a stent in their present then what you can do is after PCI you can continue aspirin and this p2y12 receptor blocker for 12 months and then you downgrade to aspirin so here's what we're going to do now so what I want you to remember is post so we'll put here post extent so they have a stent placed into their coronary vessel after they've actually been treated this you'll do aspirin and a p2y12 receptor inhibitor you'll do this for 12 months and then what you'll do is you'll downgrade to just aspirin after that lifelong or a p2y12 receptor inhibitor lifelong okay so this is going to be post stent so again when we're talking about this acute coronary syndromes first thing that we're going to do is give them aspirin and do a p2y12 receptor blocker inhibitor load second thing that you can consider is a plus or minus if they're high risk for gp2b3a Inhibitors third is anticoagulate them with Heparin if they're going to go to the cath lab the fourth thing is after if they come out of the cath lab you'll want to continue to prevent stent thrombosis so you continue aspirin and p2y12 receptor blockers for at least 12 months and then you downgrade to just one of them lifelong there's one more particular situation situation here you can consider one other drug to be given in this situation and this is usually if the patient is uh not going to be getting PCI they're far away from a PCI capable facility you can consider something called thrombolytics it's not going to be the most Superior situation here but you can consider thrombolytics such as TPA if very kind of like far from a PCI capable facility and to be honest with you far from PCI capable facility to be honest with you even if the patient does get TPA right so a patient comes in they're less than 12 hours generally that's the only time that we'll give the thrombolytics for a patient who has a active stemi so this is preferably for stemis so for a stemi that is going to be less than 12 hours you can give TPA to this patient right but again usually you try to get them to the cath lab for PCI if they are not a PCI capable facility or they're very very far from a PCI cable facility you can give them TPA but still send them to the closest cath lab that you can so they can still get a cath done for these patients so again just so we're clear because there's a lot going on here okay patient comes in with an acute coronary syndrome so unstable angina and stemi stemi all of them are going to get kind of an aspirin and a Clopidogrel load where p2y12 receptor blocker inhibitor load after that if they are going to be going to the cath lab and they're very high risk so in other words they're diabetic greater than 75 they have left ventricular dysfunction massively increased troponin you load them up with a gp-2b3a inhibitor okay if the patient's again going to Cath you want to prevent them from kind of causing any catheter thrombosis or any complications there so you anticoagulate them with heparin after they come out of the cath lab and they have the stent placed after they've had the angioplasty and stent done then you continue aspirin and Clopidogrel for 12 months and then downgrade to just one or the other lifelong for prevention of atherosclerotic cardiovascular disease and then lastly is if the patient comes to the hospital with a stemi so it's the specific type of acute coronary syndrome with a stemi less than 12 hours of onset and they are not at a PCI capable facility or they're very far away from a PCI cable facility you can give them TPA now don't give them TPA plus all this other crap okay you don't want to give them this you will kill them you'll probably make them bleed massively so if they're coming in and they are not at a PCI cable facility they're very far from one you can give them thrombolytics okay and then get them to the closest PCI cable facility as you can afterwards okay that's acute coronary syndrome the next situation here is if a patient has atrial fibrillation all right so if a patient has atrial fibrillation atrial fibrillation the problem with atrial fibrillation is these patients are at very high risk of uh embolic phenomenon okay in other words they have some kind of inadequate kind of quivering contraction of their Atria so they don't allow for adequate contraction of the Atria and so there's a stasis of blood flow and you can form left atrial thrombi so you see the son of a gun right here this is a left atrial thrombus the fear is flicking off a piece of that embolus and that goes up to your cerebral circulation you end up with a stroke to your kidney and up with a real infarct to your liver you end up with an apatic infarct to your kidneys unit you see what I'm saying you get the point that you can cause a lot of complications a lot of embolic phenomenon so I want to reduce the risk of forming clots on the actual left atrium and then again prevent clot propagation which would increase the risk of emboli so how do I do that well in this situation here you'll be like oh it's an arterial circulation antipolarials would be good no not necessarily you could do anti-platelets but they haven't been shown to be beneficial it's usually kind of aspirin as the last line if the patient has all contraindications to anticoagulants Believe It or Not anticoagulants are the best in this particular scenario so what we would do in this particular situation here is we would start the patient if they're in the hospital we would start them on something like heparin okay this is usually initially and the reason why is if we're going to start this it kind of gets us a little bit kind of a better monitoring system of these patients and we can Bridge them so we'll start off with Heparin this could be again unfractionated Heparin or it could be low molecular weight heparin and then what you're going to do is after you start them off on this so this will be kind of your initial beginning point with Heparin then what you'll do is you'll transition them just as we talked about before in the cerebral venous sinus nervosis transition them to one of the following okay if they have valvular valvular afib this is the easiest way of kind of like branching them apart in other words they have mitral stenosis or they have a prosthetic valve a mechanical prosthetic valve these patients cannot get doax it's not FDA approved it's not been shown to be beneficial so for these patient populations you go with Warfarin you go with Warfarin if the patient has non-valvular afib non-valvular afib in other words they do not have severe mitral stenosis they do not have a mechanical prosthetic valve you can do either or you can do a doac versus Warfarin it really just kind of depends on their underlying kind of comorbidity so in other words if you pick a pixaban riveroxaban a doxa band and the bigotran if they have renal dysfunction that can increase their levels and increase the risk of bleeding so Warfarin may be more beneficial again it kind of just depends but this is the way that we should look at this for atrial fibrillation a patient comes into the hospital they're diagnosed with atrial fibrillation you can start them off this is an option you can start them off with Heparin initially get them therapeutic and then once you get them therapeutic you can transition them over to a oral anticoagulant for Life long so Warfarin if they have valvular afib and you can do a doe ACT versus Warfarin for non-valvular afib okay but again the whole point is to reduce the risk of forming kind of emboli that'll go all over the place and cause things like Strokes okay oftentimes this is usually when it's found and that's why you often start off with Heparin because the patient's in the hospital because they develop a stroke or they develop an acute limb ischemia or they developed a renal infarct or something to that effect so it's important to be able to remember that all right so this is for atrial fibrillation okay next thing is what if a patient has a thrombus in their left ventricle maybe they just had an MI right maybe they just had an MI or maybe they have a reduced ejection fraction so maybe they have like an MI or maybe they have a very very reduced ejection fraction there's a lot of blood pooling up in that area this can lead to a left ventricular thrombus so there's one particular thing here all right so left ventricular thrombus but here's the other concept here these valves here mechanical valves if a patient has a mechanical prosthetic valve they're very very susceptible to forming clots very susceptible so if a patient has a mechanical prosthetic valve so if they have a mechanical mechanical prosthetic valve these are super thrombogenic and again the complications of having a left ventricular thrombus or mechanical prosthetic valve is that you can form thrombi either in the ventricle or on the valves and break little pieces of these clots off and then they can go and embolize all over the place brain cause a stroke spine cause you know some type of anterior spinal artery syndrome the leg causes acute lemoschemia you get the point so with these patients who have a left ventricular thrombus again if they're in the hospital this is why Heparin is usually most beneficial in an inpatient setting or as a bridge especially in patients who are taking Warfarin we'll talk about a little bit later but we can start off with heparin this is usually initially and again I would want to emphasize that this is we don't have to start with Heparin if a patient is atrial fibrillation and you think that they're a high risk you can start them off right away on Warfarin or a dock okay if a patient has again some type of situation up here where you want to start them off you don't want to start the one Heparin you can start them right again on a doe act whether it be a 10A or thrombin inhibitor or Warframe it's just oftentimes more beneficial if they're in the hospital and you can get some frequent monitoring to get them to therapeutic levels and then transition them over so we start them off with Heparin again this could be unfractionated Heparin this could be low molecular weight Heparin and then what you're going to do is you're going to get them therapeutic especially when you take Warfarin I'll explain why later I promise then you're going to transition and when you transition you transition to again a doack so again this is going to be one of the 10A Inhibitors the thrombin Inhibitors or you can transfer over to warfarin again it just depends on the patient so the same concept of the mechanical prosthetic valve again if the patient's in the hospital they just have the prosthetic valve placed it's often optimal to start them off on Heparin get them kind of therapeutic initially and then once you've kind of gotten that started and you've had a chance to monitor them again whether it be unfractionated Heparin whether it be low molecular we'd happen whichever one here's where it's interesting because it's a mechanical prosthetic valve what I tell you for valvular afib you only use Warfarin for mechanical prosthetic valve you only use Warfarin so you don't transition them over to a Doak you transition them to here's what's really interesting warfront and then here's one more there was some recent literature that showed that adding on aspirin as long as the patient can tolerate it also significantly reduced thromboembolic complications in patients who have mechanical prosthetic valves okay so acute coronary syndrome anti-platelets aspirin p2y12 receptor blocker inhibitor or inhibitor load them up with that first if they're at a PCI cable facility and they're high risk gp2v3a inhibitor if they're at a PCI cable facility start them and they're going to be going to PCI give them a Heparin load and then start them on that kind of infusion there after they've had the stent placed and they've gone to PCI they completed the procedure they have the stent give them aspirin and p2y12 receptor blocker for 12 months and then only one of those for Life long if they are not at a PCI capable facility don't hit them with all this freaking crap you'll kill them just start off if they're stemi less than 12 hours you start them off with TPA and then get them to a PCI cable facility as soon as you possibly can that's the ideal goal as long as it's less than 12 hours afib you're going to anticoagulate these patients left ventricular thrombus mechanical prosthetic valve you're going to anticoagulate these patients it may be beneficial to start off with Heparin if they're in the inpatient setting or you need to bridge them over to Warframe and I'll talk about why later unfractionated low molecular weight doesn't really matter and then Bridge them over if it's afib valvular Warfarin non-valvular Warfarin or doc left ventricular thrombus Doak or Warfarin mechanical only transitioning to warfarin plus aspirin okay my friends let's now move on to the pulmonary complications that we can treat for pulmonary emboli this is primarily again indication for these are the particular reasons why the drugs that we would give for this situation is going to be anticoagulants and thrombolytics and the indications of why we would give one over the other is similarly so for example for acute ischemic stroke we gave thrombolytics if the patient was in the time window in other words if a patient came at five hours I'm not going to give them thrombolytics they'll just get aspirin and they'll get a p2y12 receptor block and we'll treat their underlying cause if a patient comes in with a stemi and it's greater than 12 hours I'm not going to give them a thrombolytic okay in the same situation here pulmonary embolism it's not necessarily time it's hemodynamic stability so if a patient has a pulmonary embolism one of the things that we have to automatically kind of figure out here is is the patient hemodynamically stable or are they hemodynamically unstable if the patient is hemodynamically unstable and what does that mean that means that they are hypotensive tachycardic kind of features like that so a patient has specifically very very low blood pressure so hypotensive maybe they're super super tachycardic or bradycardic it really kind of depends and maybe they're also even hypoxic and they also have right ventricular dysfunction due to a lot of the stress on the right ventricle from this big big kind of like clot in the pulmonary circulation this is a patient who needs to get thrombolytics you can't wait you got to break this clot down preventing clot formation and continual clot propagation is not going to be helpful for this patient we gotta break this puppy down and so in this scenario if they are hemodynamically stable we are going to do thrombolytics so this would be an indication for your thrombo lytics for example again your TPA molecules okay so it's not a Time Factor as we talked about with an acute isemic stroke or for a stemi and PCI capable capabilities it's dependent upon the hemodynamics of the patient if they're hemodynamically unstable thrombolytics as long as they don't have a contraindication if the patient is hemodynamically stable then we don't really need to rush to break the clot up because in this we are going to clot bust baby we're going to bust that claw and hemodynamically stable there's no need to bust up a clot and increase the risk of the patient bleeding because TPA has the highest risk of bleeding comparison to anticoagulants and anti-platelets so now let's kind of just prevent further clot formation of plot propagation so in this situation here this is where we do anticoagulants okay so if I'm going to do anticoagulants the first thing that I would generally start off with with this patient is you can start off initially with heparin I think that this tends to be one of the more beneficial indications of Heparin especially if a patient has a pulmonary embolism we can consider again unfractionated Heparin or low molecular weight Heparin it really just depends on upon the patient low molecular weights been more beneficial in patients who have cancer and again it's even more beneficial it's removing the science thrombosis so there's a lot of different reasons there unfraction is just easier to Monitor and it's not as harsh on the kidneys but that's something that we would start with and then what we would do is lifelong if the patient needs to or not life long generally for a specific time frame uh sometimes like three to six months for the patient we would transition them we would transition to a doack so in other words we would can do like some something like a 10A inhibitor so a 108 inhibitor or we would do a thrombin inhibitor so again that's all the River Rocks band it picks the banded oxyband or the bigotran ones or we could transition them over to warfarin and this is usually Warfarin if the patient has some type of like abnormality such as anti-phospholipid syndrome it may be more Superior in comparison to a doac so that's something to consider so if a patient has a pulmonary embolism what we'll do is we'll initially start them off on Heparin maybe get them properly anticoagulated and then we'll continue and transition them over to a doe act and we won't do these life long this is can you know generally maybe anywhere from like three to six months we'll continue this therapy until it kind of resolves all right that's how we would treat a pulmonary embolism with these particular indications now let's move on to the next particular situation here which is what if we have uh thrombi or emboli and vessels of my legs or vessels in certain parts of my abdomen or things of that effect what do we do for them all right my friends the next situation is we have a lot of patients who are very high risk for atherosclerotic cardiovascular disease maybe it's because they have again very high cholesterol they smoke there's a lot of different factors we're not going to go down that route but in patients who have a clinical atherosclerotic cardiovascular disease in other words they have coronary artery disease or they've had Mis in the past or they have a Tia or they have a history of a CVA so they had a stroke at some point or they have peripheral artery disease so they have intermittent claudication at times these are all atherosclerotic plaques and the problem with these situations here is if this plaque ruptures at any point in time now the inner cheesy material is exposed and I can form a platelet plug on top of it this and if I form a platelet plug on top of this then boom I'm going to lead to a clot in an acute kind of reduction in oxygen supply to the tissues and then that can lead to a lot of problems death of the tissue so to prevent these types of Adverse Events from atherosclerotic cardiovascular disease we should use drugs that are going to inhibit the platelet blood anti-platelets and so that's where kind of like reducing the atherosclerotic cardiovascular disease risk kind of that prevention comes into play right especially in situations if they have cadmi Tia CVA or pad so oftentimes the first line agent here is going to be aspirin this is usually going to be the best situation here because again it's going to be helpful to inhibit that platelet plug an alternative you can either do plus or like so you can do and or so we'll say and or sometimes some patients may need a little extra anti-platelet blue boost slightly higher risk of bleeding but in those situations you can add on a p2y12 receptor inhibitor so sometimes we can do aspirin by itself or we can add on a p2y12 receptor blocker or we could just switch it over to a p2y12 receptor blocker really the only indication of why I would switch aspirin to p2y12 receptor blocker is they have a contraindication or they have a adverse effect from the aspirin they're intolerant to it that would be the only reason another really interesting one here so this is usually aspirin primary so I'd say that this is going to be the number one this is usually an and or in situations of really need an extra additional kick of p2y12 receptor blockers or they have an aspirin intolerance the third one here is an add-on therapy and this is solostasol so you guys remember this one you guys probably thought it was never going to come to play this is that anti-platelet that has the vasodilatory function so this is a add-on in patients who have very very very severe symptoms of pad we can add this one on so if a patient is having very terrible intermittent claudication of their legs um we give them aspirin okay and then again you can either do that plus again p2y12 receptor Blocker in really high situate like really high needs for really heavy anti-platelet blocking or you could just switch it to a p2y12 receptor blocker instead of aspirin if they have an aspirin intolerance either way we've done one or both of these if the patient is still refractor you can add on silosol for the symptoms of PD because you give an additional antiplatelet function and what's the other benefit that I want to put here in red here what's the additional benefit that Solosis all gets Sloss is all dipridam are pde3 inhibitors you get a vasodilatory function so vasodilates which may be somewhat beneficial in patients who have pad okay so I think the really important thing here to remember is that if a patient has atherosclerotic cardiovascular diseases and they're at risk for further events aspirin is the first one if they have an intolerance p2y12 receptor blocker if they really need a lot of additional anti-platelet effect because they have a very heavy burden on their atherosclerotic cardiovascular disease you can add on Clopidogrel very high risk of bleeding though and then if they have pad with refractory symptoms to the above you can add on Solosis all for the additional vasodilatory function okay now we go to the next situation you have a clot in the arterial circulation in the leg and you have a clot within the venous circulation of the leg what do we do we already talked about if there's a plaque there we give aspirin or Clopidogrel a p2y2 receptor blocker computer is more commonly utilized and then add-ons losses off if you need it in this situation if a patient has an acute um limb ischemia in other words they have an acute thromboembolus that forms and now their limb is that threat of actually dying and these patient populations what may be beneficial is to actually kind of get ready for the patient do you need to break the clot up so thrombolytics are the best but it's high risk in some patient populations and so what often tends to be the best is catheter this is what's called catheter directed TPA in other words we'll send a catheter down into this vessel and squirt TPA right in this localized area to reverse to reduce the risk of systemic bleeding so that's one really really cool interesting concept here and this will help to bust up the clot immediately okay sometimes what we may do though is we might start kind of preventing the further clot formation of propagation if we don't know if they're going to get the catheter directed TPA if they're going to go in surgically and remove it we may prep them and kind of get them ready prior to surgery or prior to whatever it may be so prior to the intervention of choice so prior to the intervention of choice you can start with heparin okay and then basically that'll just give you the time frame to prevent further clot formation further clot propagation until they go in there cut the leg open remove the clot or send a catheter down there and release a little bit of TPA and break it up or suck the clot out of the artery either way if you're going to get cathode directed TPA you can give TPA directly here until you get the procedure of choice done you can continue them on Heparin to prevent further because what is this going to do inhibit clot formation further clot formation and propagation which is really really helpful to prevent further kind of like clot burden and really reduce the actual it significantly kind of cause more ischemia to the leg all right what about in this situation a patient has a big old whopping DVT so they got a deep vein thrombosis so somewhere within the femoral the popliteal the iliac vein and it's a very heavy bird in there and now the problem is is that this clot it can actually kind of break a little piece off and then go up and cause a PE right that's one of the more common causes of PES is a DVT well in this situation here what often tends to be the best is is you can kind of like with these they're not like you don't need to break them up immediately the only time I would say that you need to cut clot bust is if the it's such an extensive DVT and it's actually causing nearby ischemia so there's so much swelling from the DVT that it's compressing nearby arteries or it's so large that it's such an intense kind of claw burden that you have to break it up you can do catheter directed kind of TPA so if it's a very very very high clot burden and it's causing significant complications you can do catheter directed TPA so you can give TPA more directly into the clot so that you reduce the risk of systemic side effects like bleeding but oftentimes you can actually avoid this particular situation because again this is going to clot bust this is if you really need to bust that clot up as soon as possible but if you don't need to claw bust and there's not that extensive of a clot burn they don't have extensive kind of like a ischemia as a result of the DVT which is very serious they have that then what you can do is you can instead as an alternative so what what would generally be the more common approach so generally let's say that the patient is and not in this particular scenario what we would do is is we would start off with heparin okay we'd start off with Heparin and again you could do unfractionated Heparin or you can do low molecular weight Heparin get them therapeutic and then afterwards you can transition you can transition to one of the following a doac which is going to be more commonly preferred so this is usually way more preferred over Warfarin or you can do Warfarin or Warfarin and the only time this would be perverted the patient has antiphospholipid syndrome as a result and we don't do this lifelong this may be for like anywhere from like three to six months three to six months okay so it's important to remember if a patient has a DVT and it's a heavy heavy heavy clot burden there is one little caveat to that situation where you can give TPA but you don't give it IV you actually direct the catheter right to where the actual big clot is in the DVT and squirt the TPA there if it's not a heavy heavy claw burn where the patient is actually developing ischemia due to the DVT which is not common but if it is that's very severe then we can go this route where we actually heparinize them to prevent the clot from getting bigger and propagating and then transition them over to a doe act or warfarin to allow for the claw to break down slowly over time and again prevent the risk of the PE okay the last type of vascular event here for peripheral and then Central here is this isn't a really random one I'm going to quickly go through it because it's not super common uh it's mesenteric Venous Thrombosis so mesenteric Venous Thrombosis you usually see this in patients who have a lot of hypercoagulable conditions or cancer and what happens is they develop a clot with inside of their mesenteric vein and that can lead to a lot of problems that can lead to portal hypertension it can lead to ascites it can lead to a lot of different nasty things so in this situation it's a venous clot treat it with anticoagulants that's the best situation there so oftentimes with this one what we'll do is we'll do everything that we've got to continue to talk about here it's going to be ingrained into your heads so initially we'll start off with Heparin and again this can be unfractionated Heparin or low molecular weight Heparin just remember lower molecular weight Heparin is a little bit better in Cancers and then afterwards we'll transition and when we transition here's what's a little odd you only transition to warfarin for mesentery Venous Thrombosis so I thought that was an interesting one that I wanted to quickly add in so I think that's important to understand here when we're talking about again preventing these further events if a patient has had these events and they're at risk for another one you need to get them on anti-platelets to prevent the clot propagation on the plaque if it ruptures especially aspirin you can consider p2y12 receptor blocker as an alternative if they have an intolerance you can add it on if it's a very very heavy you know atherosclerotic burden plus the losses off their symptoms of pad or refractory Cuba ischemia if you've got to bust the clot up immediately send a catheter down to square TPA don't give it systemically because it has a high risk of bleeding if you need to give them something to prevent the clot from getting any bigger or getting any larger you can keep them on Heparin until you go in surgically cut the clot out or aspirate It or Break It Up with TPA DVT if the burden is so high that the DVT is so big that it's compressing it's so intense that it's causing so much swelling that it's compressing the nearby arteries and causing ischemia you can go in with a catheter and direct TPA right to that clot and break it up but if it's not that bad you can continue to prevent the clot from forming and propagating a lot for to break down over time with Heparin and then transition them over to a Doak or Warframe about three to six months and then lastly mesenteric Venous Thrombosis clot within the mesenteric vein can cause a lot of ascites portal hypertension a lot of problems like that in this situation Heparin initially to break uh to kind of prevent clot formation and propagation and then switch them over to something like Warfarin and the time duration really depends for these patients it could be anywhere from three to six months as well all right let's go on to the next thing which is a patient who is at risk of developing a DVT and a subsequent P how do we treat that all right my friend so the next situation is what if a patient is at risk uh developing a DVT that can actually break off and then cause ape that's a that's a pretty nasty situation right so if a patient has risk of kind of forming a clot here within their deeper veins of leg so femoral iliac popliteal and then that piece of it breaks off moves up via the what inferior vena cava and then pumps up into the right atrium and into the right ventricle and then you get a big old pulmonary embolus so there's two potential kind of complications from this is that you can have a patient Who develops a DVT and then subsequently develops a PE so I think you have to be willing to understand which kind of patient population is a very high risk for developing dvts and PES and that's patients that are going to generally kind of be like post-operative so sometimes we're post-op who are you know especially bedridden okay so they're bedridden patients who have increasing like malignancy so there's a lot of different kind of like factors here but I think when it comes down to it there's three particular reasons of why patients develop clots within their venous circulation if you guys remember it it's patients who again have stasis of blood flow they have hypercoagulability or they have endothelial injury now when patients are especially in the hospital are bedridden they're not out of bed they're not ambulating they just had a surgery done in these particular scenarios they are very high risk of forming clots especially because of the stasis Factor and because of endothelial injury from whatever procedure that they had done to them is because of that we need to be able to consider what can we do to prevent the risk of clot formation in the subsequently clot propagation and the venous circulation yes this is arterial circulation here but again venous that's connecting to the actual pulmonary arterial circulation anticoagulants and so oftentimes yes out of bed getting them ambulating is ideal but if the patient isn't able to get up out of bed they aren't able to ambulate and provide a movement then in these situations you need to try to give them chemical prophylaxis from getting a DVT and subsequently a PE and so oftentimes there's two ways that we can go about this one way is we can get very low dose heparin okay so we can get very low dose Heparin again this can be unfractionated Heparin or it could be low molecular weight Heparin it really just kind of depends which one's preferable for the patient population but that would be one particular option here low dose Heparin and again this is usually given subcutaneously okay another option is is if a patient is on um let's say anti-coagulation for an under for an underlying disease so for an underlying disorder that can serve as VTE prophylaxis so let me give you an example of number two so an example here of number two which I think is very important here for number two as a patient has atrial fibrillation okay so a patient has atrial fibrillation and they're taking some type of situation here so the patient has atrial fibrillation and they're at risk of left atrial thrombus so if they have afib they're going to be on let's say riveroxaban which is one of those 10 a Inhibitors okay that riveroxaban is particularly used to prevent left atrial thrombus but on top of that you'll also get a VTE prophylaxis for it so you're going to get two benefits for this is you're going to get atrial fibrillation coverage to prevent a left atrial kind of like thrombus and then subsequently emboli but you can also cover VTE prophylaxis to prevent dvts and subsequently PES that's a pretty cool concept to remember so if a patient is not on full dose anticoagulation for an underlying disease you should start them on one of these whether it be low dose subcutaneous unfractioned or low molecular Heparin but if they are on full dose anticoagulation then you can just again realize that this is treating one of their disorders but also getting VT prophylaxis you don't have to give them both I think is the key thing okay so it's one or the other all right my friends let's now talk about the last and final indication of why we would use anti-platelets anticoagulants and again thrombolytics all right my friends so the last situation here is that we can use some of these drugs to prevent clotting of like a lot of like circuitry and catheters and such and such uh so one of the kind of quick reasons here if a patient is on some type of like situation where they're on heart lung machine so if a patient is on like ECMO so extra corporeal membrane oxygenation um or they're on something like uh cardiopulmonary bypass so cardiopulmonary bypass these are Big stinking catheters and a lot of circuitry that's really dependent upon not clotting off okay so if you have a patient who's not anticoagulated in other words you don't have a lot of anticoagulation running through it can clot off the catheters it can clot off a lot of the circuitry between the ECMO and the cardiopulmonary bypass system so in these particular scenarios here you want to prevent kind of a clot developing within one of the circuitry that's running in and out of the body so in this particular scenario we prefer Heparin and really when it comes down to it it's preferable to have unfractionated Heparin greater than like more preferably in comparison to low molecular weight Heparin because you have a way closer titration it's not as harsh on the kidneys so that would be a particular situation there the last one here is in patients who have central venous catheters so if you have a central venous catheter that's placed in the femoral vein or the internal jugular vein or for the for the good ones the subclavian vein and those catheters become clotted off so sometimes you can get a thrombosis within the catheter and in those situations the catheter is not functional you aren't able to get things through so in other words if I wanted to run IV fluids through this catheter and at some point in the catheter there's a clot within the catheter it's not able to deliver the IV fluids into the right atrium so in those situations I want to reopen up that catheter and get rid of that clot so in these situations where a patient has a clotted central venous catheter one of the situations that we can do for this is Infuse a very very low dose of TPA to indwell within the catheter and so what it'll do is you'll have the catheter kind of just directly if you think about a catheter directed a little bit of kind of TPA come right here to where the clot is and break that clot up and restore flow to the catheter so you can allow for flow to move through so in this situation we give very very low doses like I'm talking like two milligrams of TPA to be able to bust open the clot within that clotted central venous catheter okay so this is the concepts that I want you guys to understand here for the indication so we have gone through neurological cardiac pulmonary peripheral central vascular we went through VT prophylaxis preventing clotting off of circuitry and very important central venous catheters and when we talk about a lot of these things I need to come back to one really important point that I just I I sometimes feel like when we go through all the depths of these mechanisms we can forget it when we talk about anti-platelets and anticoagulants they're really again blocking the platelet plug right they're blocking that platelet plug and they're also blocking the formation oh sorry blocking the formation of that fibrin mesh right and by doing that the overall concept for these two drugs here is that they are inhibiting clot formation and they're also inhibiting clot propagation they're not breaking down a clot if you need to acutely break down a clot that is where thrombolytics come into play they help to break down the fibrin which alleviates the fibrin mesh and they also help to break down some of the fibrinogen that's helping keep the platelets kind of stuck together is also breaking down some of the fiber that's actually keeping the platelets kind of like nicely tight against this plate of the plug and that will dissolve and break down the clot so this will actually dissolve dissolve the clot okay so that's an important kind of concept to take away from this guys and the real true layman's terms of it all right now that we have gone through the mechanism of action with relationship to the physiology we've gone through the indications of these drugs in extreme depth what I need to now talk about is adverse effects some generalized one for each category and then the most feared complication of giving an anti-platelet anticoagulant and most importantly a thrombolytic is the patient is going to bleed so let's talk about all of these one by one all right my friend so now let's let's actually go through and be very thorough and talk about if we put a patient on one of these particular medications an anti-platelet anticoagulant a thrombolytic what are some of the adverse effects obviously the most feared one the most dangerous one the most common one is going to be bleeding we'll save that for last because that's obviously the easiest one to understand you give someone that's trying to you give them a drug that's either trying to stop clot formation or prevent clot propagation or or breakdown clots there's always going to be the risk of inadvertent bleeding we'll discuss that a little bit later additional adverse effects that you want to think about and consider that you definitely may see on the exam now is what we're going to talk about so first one acetyl acetyl salid gas are aspirin this is that Cox enzyme inhibitor now with this drug one of the first things to think about is if a patient has severe peptic ulcer disease you can worsen their peptic ulcer disease you can worsen the peptic ulcer disease the reason why is when you give aspirin there's a specific molecule here so you know you have what's called arachidonic acid and it's used to make something called pge2 which helps to be able to stimulate kind of a mucous production within the stomach lining so it kind of coats the stomach lining and prevents kind of gastric acid erosion right now if you give somebody now this pathway is dependent upon the cycle oxygenase enzyme it stimulates this pathway so if you give him aspirin what it's going to do is it's going to inhibit this enzyme you'll decrease the production of pge2 and you'll decrease the mucous production which is that barrier if you don't have this barrier now now that gastric acid can start kind of eroding through the actual stomach leading to these gastric or duodenal ulcers which is the pathology that we could potentially see here okay so with peptic ulcer disease this could potentially increase the risk of peptic ulcer disease or worse in a patient's underlying present peptic ulcer disease okay next thing this one's kind of rare but it's worth mentioning there is a disease called rye syndrome now with Rye syndrome this is usually occurring in patients who are less than 19 years of age now there's two potential things here they're either they're less than 19 years of age and they have a viral infection of some etiology and they have they're taking aspirin in combination so this is kind of that Triad thing there so Rye syndrome is a less than 19 year old child with a viral infection who takes aspirin okay usually the family member may give them the aspirin not realizing this potential etiology because they have a fever like okay here take some aspirin instead of Tylenol the reason why this is a problem is because the combination of the viral infection and aspirin in this child can lead to real significant damage to the liver and the liver then loses the ability to metabolize and clear a very special molecule so your liver takes something called ammonia and converts it into something called urea which will then go to our kidneys and our kidneys will then kind of pee that molecule out right so that's generally the design one of the design functions of the liver so this will then go to the actual kidneys and then you'll pee the urea out now if you damage the liver you lose this capability and then the ammonia levels build up when the ammonia levels build up this causes a lot of damage to your actual central nervous system and this can lead to cerebral edema this can lead to seizures this can lead to an altered mental status a lot of scary scary things that you can see within this patient population and on top of that the liver also loses the ability to clear lactic acid and so usually lactic acid is another molecule which will get taken up by the liver and then convert it into something called pyruvate right so you convert this into something called pyruvate which can be utilized to you know make either break it down into you know generate ATP or convert into other Pathways but if you lose the ability to deliver to do this then lactic acid builds up and this can lead to an anion gap metabolic acidosis so things to watch out for in this patient who can develop Rye syndrome is if they are less than 19 year old child who has a viral infection takes aspirin and develops an anion gap metabolic acidosis cerebral edema with increased intracranial pressure seizures and altered mental status these are things to think about aspirin again kind of modifies the arachidonic acid pathway right and because of that what it'll do is it'll inhibit kind of so generally when you think about this this can one of the other things about aspirin is it can increase what's called um acute asthma exacerbation of respiratory diseases so it can really kind of like worsen like sinusitis and nasal polyps and Asthma and things of that effect and the reason behind this is that aspirin similar to this process above is you take arachidonic acid and it can get broken down into two Pathways one doesn't get broken down to like what's called prostaglandins or thromboxane kind of A2 right and then the other one is leukotrienes now this pathway here going to throw unboxings and prostaglandins is dependent upon cyclooxygenase this one going to leukotrienes is dependent upon lipo oxygenase aspirin only really inhibits the cyclooxygenase and so you decrease this pathway but then you have all this arachidonic acid that can't go here and so it shunts it into this pathway and so you make lots of leukotrienes problem behind that is that lots of leukotrians cause a lot of inflammation it causes kind of bronchospasm it can cause a lot of these problems that worsen things like nasal polyps and sinusitis and Asthma and so that's really the kind of the problematic issue here is that with this increase in leukotrienes you get this increase in inflammation and you know permeability and vasodilation capability problems that you see with this disease okay that's the big thing now the next thing that you want to understand here is if a patient actually takes way too much aspirin maybe it's a suicide attempt maybe they don't realize it and they take just a large dose of aspirin or they're having pain or some potential problem they just take way too much and they develop toxicity you should be able to recognize this how do we recognize this all right next concept here is a patient actually takes way too much aspirin and they develop toxicity some of the mild side effects that aren't really bad and you can actually remember this is kind of like a Triad there's always these dang Triads but it's usually nausea um vomiting and tinnitus so kind of ringing in the ears this is usually the Triad this is usually mild it's not going to require any kind of a you know aggressive treatments but if they progress to moderate to severe toxicity what happens is aspirin really Alters a lot of like metabolism of things around the electron transport chain and this can lead to a massive increase in lactic acid and it can also increase the production of Ketone bodies and the combination of an increase in ketones and an increase in lactic acid leads to an anion gap metabolic acidosis so that's one potential thing that you can see the second thing is that aspirin may actually stimulate an increase in your respiratory drive so if your respiratory drive Center which is controlling kind of your inspiratory Cycles like your respiratory rate and depth if this is increased you'll increase your respiratory rate and depth and so you'll breathe really really fast and this can create something called a respiratory alkalosis one other potential etiology and we don't know how exactly it does this but aspirin May directly cause damage to the lung parenchyma and lead to pulmonary edema so it may lead to what's called non-cardiogenic pulmonary edema so other things to watch out for is anion got metabolic acidosis as well as a respiratory alkalosis as well as non-cardiogenic pulmonary edema and then one more thing aspirin toxicity can also kind of cause a lot of you know injurious type of problems with the central nervous system where it can produce things like alter mental status it may produce confusion and it may even induce possible seizures so it's something to be able to think about so watch out for these potential complications if a patient has toxic side effects from taking way too much aspirin if they do generally the treatment of choice here is to give them IV fluids to give them sodium bicarbonate to try to alkalinize the blood so you're trying to really increase the pH of the blood because right now their Peach is really low and then lastly is if the patient is really really severe you can consider something called hemodialysis to dialyze off all of the aspirin okay all right my friends that's the adverse effect that we really want to be careful with when we talk about aspirin let's now move on to the next group The p2y12 receptor blockers all right my friends so the next thing here is when we talk about p2y12 receptor blocker so this is your capitagro this is your presug rule this is your taclopidine this is your ticagrelor one of the big things to think about with these particular drugs is is again especially to clopidine especially to clobidine there's a risk of something called TTP okay so there is an increased risk of the disease process called TTP thrombotic thrombocytopenic purpura now in TTP what's the underlying kind of reasoning behind this there is a protein that our body has and it's called atom ts13. and what this protein really does is it actually breaks down so it actually will inhibit what's called Von wildebrand Factor so it'll break it down so generally like you have what's called Von wilderbond Factor that's usually going to be kind of let's say that there's kind of like a Von Willebrand factors that are kind of expressed here platelets love to bind onto that right and so what it does is it breaks down Bond wilderbond factors that you don't have a lot of places for platelets to be able to bind to because if you have a lot of Von wilbron Factor proteins that's a site where the gp1b proteins love to stick to the Von wood run Factor so that's basically trying to prevent unnecessary platelet aggregation all right so this basically will inhibit or decrease platelet kind of activation or and plug right kind of formation well here's the problem if a patient has Tate is taking let's say they're taking to clopidine all right they're taking one of the actual p2y12 receptor blockers but I'd say the most significant one to be able to remember I can't stress this enough guys is to clopidine you can see it to a smaller degree with the other ones just not as common so here we're going to have a p two y12 receptor inhibited that the patient is taking what's the most common one again say it out loud to clopidine what happens is this this drug can activate our immune cells to produce maybe some Auto antibodies and these Auto antibodies are antibodies that are directed against atoms ts13 . so now these antibodies are going to go here and lead to the destruction or decrease in the actual presence of atom ts13 now if there's less atom ts13 can you break down the Von wildebron Factor no and so Von wildebron factors won't be broken down and so you're going to have an increase in the Wilder bronze Factor if you have lots of wildebron factor now the problem is is that you have lots of sites now these little proteins that playlists love to stick to and the pleats will stick they'll become activated they'll release these molecules like ADP thrombox in A2 and cause other plates to come stick with them and form a platelet plug and then the problem here is that you're going to increase the platelet activation aggregation and the platelet plug formation and then subsequently what do you develop you develop a clot or a thrombus so then you develop thrombi oh man this ain't good man ain't good man because then now if I make all these thrombi guess what's going to happen these are going to form all over the dang place so here's my arterial circulation I'm going to have all these thrown by just formed everywhere here's the problem with this now if I have all these thrombi formed within all these micro vessels when blood is flowing through there it can shred apart red cells shred apart platelets this can block off blood flow to the kidneys and lead to a lot of problems in the brain and so the complications that you want to remember is fat RN what Zach what'd you just say I know it's a terrible thing but it's the way that you can remember kind of the classic features of TTP is fever anemia thrombocytopenia renal failure and neurosymptoms so let's write that down again what are the potential features here that you could see fever could be a cytokine response anemia due to ripping up the actual red blood cells as they run through here thrombocytopenia which is they're getting consumed within the actual formation of clots renal failure because it's actually blocking off blood flow to the actual kidneys and neuro symptoms this is a really really important concept okay so if a patient is taking a p2y12 receptor blocker and all of a sudden they develop thrombocytopenia with Associated fever anemia again renal failure and some type of neurological symptoms such as altered mental status fever Strokes things of that effect they could potentially have TTP because of that drug think about that and then oftentimes we treat these patients with what's called Plex so we do something called plasma exchange we basically clean their blood and get rid of all of the actual p2y12 receptor inhibitor and get rid of these Auto antibodies that are really the problem okay sometimes you can even consider other things as well but like you know steroids in that effect but generally Plex is going to be the the best situation here one other thing here is that some of these drugs especially to clopidine may also suppress the bone marrow exactly how unsure but I think the big thing to remember here is diclopidine is a bad drug don't use it and when you use to clopidine one of the things that it can do is it can inhibit the bone marrow from producing red blood cells so they can experience anemia and they can also experience neutropenia so watch out for neutropenia and also watch out for just generalized anemia as well all right one more kind of adverse effects we talked about TTP we talked about bone marrow suppression with taclobodine the other thing to remember here is that some of these drugs especially really really important here Clopidogrel so Clopidogrel can have what's called a cyp 2c19 polymorphism you're like what in the crap this is usually seen with again what particular drug out of all of these so again we had pursue Grill we had ticagrelor we have Clopidogrel we have to clopidine this is primarily seen with Clopidogrel so some patients have mutations in this cytochrome enzyme found within the liver so this is going to be your liver your liver has the cytochrome p450 system this is one of them cyp 2c19 and what it does is it takes Clopidogrel and it actually will activate it so this is the pro drug and it'll be converted into the actually they're active drug okay via this particular enzyme some patients may have variations in other words they may have one form of this where they have increased activity some patients may have increased activity of their cyp 2C 19. and if that's the case they're going to rapidly metabolize this Clopidogrel into the active drug and if that's the case they'll have increased response there'll be increased responders to Clopidogrel in other words they may have a slightly higher risk of bleeding but they'll respond really really well to that drug the other way is that you can think about another polymorphism so there could be increased activity but there also could be decreased activity and this is again all based upon like genetic factors here of the cyp 2c19 that means that this enzyme won't perform very well it won't convert the pro drug into the active drug and they'll be poor responders poor responders two Clopidogrel how do we really tell this though is there any test that we could actually utilize man that would be cool if there is and yes there is one of the tests that we can actually utilize to analyze if a patient is a good responder or a poor responder to the clip interval because there is this variation or polymorphism in this Gene is we can check what's called a p2y12 level so if I checked it in this patient population I would check their P2 y12 assay and typically in these patients if they're really you know good responders they'll have low p2y12 levels because you're really inhibiting that receptor if it has very low activity decreased activity of this Cy this enzyme now they're p2y travels y12 levels will be very high because they're not going to be having as much inhibition of this particular receptor because what we're doing is we're testing the platelets for this particular receptor and if there's a lot of inhibition of it meaning that they are what good responders it should be low and if we actually have poor responders they should be having high p2y12 levels so that's something that we can check all right my friends that's the things we have to watch out for this drug category okay one other thing to add on here just as a quick aside is that bleeding risk when we talk about bleeding with respect to Clopidogrel versus toclopidine versus prosugarl versus ticagrelor I think one thing we're going to talk about bleeding risk in a second but I think it's important to remember that prosugural anticagrelor have kind of some degree of increased risk of bleeding in comparison to all the others so I think it's important to remember for these two they have a high bleeding risk almost to some degree even especially the prosugural a black box warning for the bleeding that they could potentially cause so just be aware of that Clopidogrel not as much but to kagrelor and pursue or especially pursue Grill here let's actually do that as well prosugural even more so than to kagrelor have higher bleeding risk associated with it okay let's come down and talk about the next group The pde3 Inhibitors so the next one here is the pde3 inhibitor so this is the cilostazole and dipyridamole now with these because they do cause vasodilation they can actually dilate the cerebral vessels and so because there may be some degree of like cerebral vasodilation it may kind of cause them to bang on the noisy receptors in the dura mater so if you dilate them there may be a lot of noisy receptors nearby when you dilate these and here's the dura matter right here so there may be like little pain receptors when you dilate this vessel it may now Squish and press down on some of these like pain receptors and noise receptors that are nearby and that may lead to headaches and so because of that one of the things that you want to watch out here is that the patients could potentially develop headaches here's one more this is really important I think it's really something to consider is that there is an increased mortality of uh in patients who have CHF if you utilize these drugs so if a patient has some type of heart failure whether it be a heart failure whether reserved or reduced ejection faction it's been shown that this drug category can potentially increase mortality so avoid it that's just all I can say about that are we covered to see the salicylic acid or aspirin cover PUD acute exacerbation of respiratory diseases Rye syndrome right we talked about the toxicity effect and then we went over p2y12 receptor blockers watch out for TTP especially with diclopidine bone marrow suppression with diclopidine watch out for the cyp uh 2c19 polymorphism with Clopidogrel because you can have some people who are poor responders and good responders you can assess that with the p2y12 level and then again we talked about patients who are taking these just be careful more specifically with prosugural and with decagler they're going to have a higher bleeding risk in comparison to to clopidine in comparison to Clopidogrel and even in comparison to acetylsalicylic acid okay let's now move on to the next thing which is going to be Heparin all right my friends so now we're going to talk about Heparin so this is going to include again your unfractionated Heparin your low molecular weight Heparin and technically if you even wanted to add that one in there you can even consider fond of paranox so when we talk about these one of the big things that you want to think about and I think this is really the most common with unfractionated Hepburn more than you're going to see in low molecular weight Heparin and way more than you're going to see in fond of paranox is a disease called heparin-induced thrombocytopenia we call this hit so again I want you guys to think about a disease here called heparin-induced thrombocytopenia so we'll write this one right here so Heparin induced thrombocytopenia with heparin-induced thrombocytopenia obviously it's induced by Heparin and when you see this is again how does this all happen how does this really happen all right so let's say that a patient takes Heparin and again I think it's really important to establish which one of these is really going to be the more common type that's really really important because if it comes up on your exam you need to be able to identify that so here we're taking a patient they take some medication called Heparin gets into their bloodstream if we're going to look here it's going to be unfractionated Heparin is going to be more common this to induce this then low molecular weight Heparin fauna paranox pretty much almost a nil okay but if you wanted to it would even be less common than low molecular weight heparin so they take this drug when they take this drug what happens is the heparin will bind with something called platelet factor four okay so here this is going to be the Heparin and what the Heparin is going to do is is it's going to combine with something let's draw this in pink here it's going to combine with something called platelet factor four so now I have these two molecules that are going to kind of complex together when they complex together what it does is it forms an immunogenic complex it's very immunogenic and it activates our immune system cells and our immune system cells will develop a response to this kind of complex and start producing antibodies against this complex so now if I look over here I'm going to have this complex here here's the heparin okay here's the Heparin that I'm taking in and again which one more commonly unfractionated over low molecular weight Heparin which is way more common than Fonda paranox and then if I were to kind of like draw like a binding connection here we'll do this with black here here's going to be the heparin heparin and it's combined with platelet factor four it's combined with this thing called platelet factor four it stimulated this immune system response the immune system when activated produced these antibodies and these antibodies are like um I'm going bind to you and then look it's going to bind onto this kind of complex here when we bind onto this and now we have the antibodies bound to this now it's kind of having you have these I G G antibodies which are bound to happen and platelet factor four guess what it does it then sticks to platelets and now it's going to activate platelets so now you're going to have this whole complex and what you're going to do is you're going to have this whole thing bind onto platelets so here's going to be a bunch of platelets when this kind of binds onto the platelets it's going to activate all of these platelets when they become activated they're going to want to stick together when they stick together and they activate and they start causing all of this problem guess what you're going to get a big old platelet plug and then subsequently a thrombus formation so now I have this connection here I increase I actually have this platelet factor four which binds with the Heparin my immune system produces IGG antibodies that binds with this this binds to platelets it increases the activation of platelets increases the formation of the platelet plug and increases the thrombite to form now look at this I get thrown by forming all over my vascular system and here's the problem in comparison to DDP it forms in the arterial circulation and oh man and the venous circulation this is a No-No because if I get thrombed by all over the dang place here this is a big situation if I get in the arterial circulation this can cause an MI if it gets stuck in the actual cerebral circulation it may cause a stroke if it gets stuck in the leg it can cause an acute limb ischemia if it gets stuck in the venous circulation it can cause a DVT if it gets stuck in the DVT and then it breaks off and causes a pe oh my gosh this is a terrible situation to occur so heparin-induced thrombocytopene is when a patient takes heparin when they have the Heparin they bind it with something called platelet Factor 4 which is expressed on platelets IGG antibodies then bind to that Heparin and platelet factor four complex which is present here so now look look at this here's the Heparin here we're going to draw in red here's the playlist Factor 4 which is bound to the heparin and then now we're gonna have all these IGG antibodies that are stuck to this and it's going to create this kind of activation platelets and lead to an increased clot which is going to form an arterial and venous circulation can lead to arterial and venous thrombi on top of that whenever you give Heparin you give it subcutaneously so generally with the Sub-Q injections especially with the Sub-Q injections one of the things that you may see around the injection site where you're giving the Heparin is it may produce some skin necrosis around the injection site so this is really adding to the diagnosis so if a patient has arterial thrombi Venus thrombi skin necrosis around the injection site and then one more thing when you consume when you actually kind of cause these platelets to form a platelet plug you consume the platelets so this is going to lead to consumption of the platelets so what this is going to do is it's going to cause a consumptive drop in the platelets a thrombocytopenia if you will this is the fourth Factor these are all factors that you want to remember for a patient who has heparate induced thrombocytopenia okay if this develops you discontinue the Heparin okay so discontinue the heparin and then switch them over to another molecule if you still have to anticoagulate the patient you've got to give them something so give them something that won't interact with that won't be a Heparin molecule or will interact with antithrombin 3 and all these kind of problems so you would think oh what about direct Factor Inhibitors wooden Factor 10A Inhibitors work you would think but they're oral and so you're like okay well if I can't give the oral one which one's where the IV ones oh wait what if it's the thrombin Inhibitors that are Gator banded by valaru and that was the IV one you probably want to give this because these patients are critically ill right absolutely so in this scenario you prefer to give the thrombin inhibitors and the reason why is you want to give the IV version and the IV version is going to be what's called our gatroban our gatroban and another one is called bivala root so in these patients discontinue the Heparin and switch them over to a thrombin inhibitor that is IV for critically ill patients if they're not as critically ill you can potentially consider the oral medications like the oral thrombinibers like the bigotrant or the oral 10A Inhibitors like River Rock's benefits of benadocent but generally this is the more critical situation here all right another concept here one more going off of Heparin here is that when we talk about these drugs um I think with respect to kind of comparing the two so let's say here I have unfractionated Heparin and here I have low molecular weight Heparin sometimes this is an important kind of like concept to understand is what really comes down to the difference in these drugs and which one do you prefer one of them is unfractionated Heffron Heparin Heparin unfractionated Heparin really isn't um as much of a damage on the kidneys so it's less risk um of you know problems with renal failure in other words in less risk of increasing levels in Aki and CKD in other words if a patient has Aki or CKD you don't have to adjust the dose of unfractionated Heparin which is nice whereas with low molecular weight Heparin you have a higher risk of increasing levels n Aki and CKD and so you'll have to renally dose these particular drugs so if a patient has underlying chronic kidney disease or acute kidney injury I would say no to giving them or be very careful with low molecular weight Heparin whereas if they have it in this situation you're okay with giving unfractionated but it's more preferred another thing it comes down to is um Half-Life unfractionated Heparin is very a short half-life so what what's important about that is that it makes it very titratable very titratable agent okay whereas something like low molecular weight Heparin this has a relatively longer half-life so it's not as easily titratable and that's why whenever we have patients who we need to have a very very tight control of their anticoagulation we may prefer unfractionated Heparin because this makes it more likely to be an infusion whereas this is not going to be an infusion that's usually going to be like once or twice a day that we would give this particular drug all right one more thing here is that low molecular weight Heparin tends to be superior in patients who have cancer in comparison to unfractionated Heparin so an unfractionated Heparin it has less kind of effect in cancer whereas in low molecular weight Heparin it's going to have increased efficacy and cancer another concept here is that with low molecular weight Heparin we can really do this relatively well since it's a longer Half-Life it doesn't have to be kind of an infusion you can give this as a injection outpatient so because of this kind of Half-Life and this ease of titration it makes this a more reliable outpatient medication whereas since this has to be an infusion it's more reliable as an inpatient type of medication okay just a couple things to really kind of like add on here since we're talking about anticoagulants here okay my friends we've now covered with Heparin we covered Heparin juice normal cytopenia things to watch out for with that one we talked about what we would switch to if that happens we talked about some other kind of like small differences between unfractionated upper and low molecular weight Heparin especially with kidney disease Half-Life which one's preferred for inpatient outpatient and which one's a little bit better and more efficacious in situations such as cancer okay now let's move on to the other ones which is going to be your direct oral acting anticoagulants the 10 and thrombin Inhibitors and then we'll talk about Warfarin all right next thing is dox so this is going to include again your um your direct acting so this is going to be your 10 Inhibitors so your 10A inhibitors and this is going to include your thrombin Inhibitors right so riverox banapixabandadoxaban the bigotran by Valerian or gatroban all those Sons of Guns one of the biggest things to be honest with you they don't really have a lot of like complications their risk of bleeding is a lot lower than the vitamin K antagonists like Warfarin um but with these they're really dependent upon renal function since they're really excreted if a patient has some type of chronic kidney disease or they have an acute kidney injury one of the downside about this is it can actually lead to the increasing levels of this drug similar to low molecular weight happens so it can increase the levels of the doe ax and can therefore increase the risk of bleeding one other thing to go along with this just as an aside because you may you may see this is that out of all of these 10A Inhibitors and Factor two Inhibitors or the thrombin Inhibitors only one one of these drugs can be removed by hemodialysis so if a patient is taking is on hemodialysis there's only one out of all of these drugs that can actually be removed do you guys know which one is actually able to be removed by hemodialysis this is the bigotrant okay it is the only one that can be removed out of all of these direct acting oral anticoagulants that's the only one all right that's it for that one the next one is your vitamin K antagonist now with vitamin K antagonists this is really just Warfarin this is your Warfarin what are some big things to think about with this one watch out for teratogenicity okay this one you should not give to patients who are actually pregnant the reason why is it crosses the placenta if it crosses the placenta that could be absolutely disastrous so this can actually cross the placenta if that drug Clauses crosses the placenta it can increase the risk of fetal bleeding so this can increase fetal bleeding and then fetal demise so that's one particular contraindication that you would not want to give this drug in do not give it to someone who is pregnant the second thing here is that Warfarin is heavily metabolized by cytochrome p450s enzymes and there's a lot of other drugs that are as well and so this really comes down to really safety because there is a lot of drug interactions and I think this is worth mentioning the reason why is if a patient is having many medical issues they may be on Warfarin for atrial fibrillation or because they have some other disease process that we talked about and if they're on that but they're also taking a medication for another disease that they have maybe they have an arrhythmia that drug that they could be taking could alter their levels of Warfarin and that's dangerous because Warfarin operates in a very narrow kind of therapeutic window and if we increase the levels of our Warfarin we could potentially cause bleeding if we keep it less than the levels that we want they could clot so it's very very critical that we understand that so there's a lot of things that can alter this cytochrome p450 system so in this situation it's different from Clopidogrel we go from the inactive form sorry so we go from this drug we're going to kind of metabolize it right and so whenever you metabolize this drug you go from its activated form and then you inactivate it unlike the pro-drug like Clopidogrel it went from pro drug to active drug I think because understanding that Warfarin can be metabolized by this it can be altered in some particular way so what do I mean let's say I have one drug category we're going to call these Inhibitors so they inhibit the cytochrome p450 system so if we imagine here let's draw this as kind of like a little dot here this is going to be this Green Dot so whenever this Green Dot binds into this socket here it inhibits the enzyme from actually metabolizing and breaking down Warfarin so if that's the case what would that do to the levels of active Warfarin if it can't go through this it's going to increase the levels of Warfarin which increases the risk of bleeding oh shoot so because of that I really should know some of these drugs I want you to remember Pam any of you guys watch the office you'll know what that means but Pam we got proton pump inhibitors amiodarone azols acetaminophen and then macrolides and I think these will cover kind of the more common categories of drugs and so these if they bind onto this they'll inhibit the enzyme they can't metabolize it that's that's really important so I want you to remember that this is going to increase the levels of Warfarin which increase the risk of bleeding now take the other indication other situation here we have an inducer and so in an inducer let's pick another color for this one let's just do this kind of like blue here with this inducer it can bind on here and what it'll do is it'll stimulate this enzyme to increase the metabolism and so then I'll decrease the actual levels of the active drug and increase the levels of the inactive drug so I'll basically metabolize the Warfarin and decrease the levels of the warfarin so that's important so what's this going to do it's going to decrease the levels of the warfarin this you can remember CPR okay so some of the drugs in this category there's a bunch the you know but I think these are some of the more commonly utilized ones so this could include carbamazepine which is an anti-epileptic and using trigonal neuralgia another one is called phenytoin we'll put PHT and then another one for tuberculosis is Rifampin so I think these are really important things to be able to remember my friends okay teratogenic please don't give it in that increased risk of fetal bleeding and demise and then again drug interactions things to watch out for that actually can increase the levels or decrease the levels of Warfarin one more thing there's something called Warfarin induced skin necrosis so what is this called it's called Warfarin induced skin necrosis can't say I've ever seen this but it's something to think about whenever somebody develops whenever somebody takes Warfarin what we know is is that Warfarin inhibits the vitamin K epoxide reductase which is going to basically decrease the synthesis of a lot of functional proteins so some of those were pro-coagulant so we'll put them up here so some of these are pro coagulant factors two Factor seven factors nine factors 10. right these are wanting to induce clots the other ones are protein C and S these are anticoagulants here's what happens when protein C and protein s naturally are produced what they do is they kind of are circulating through the blood so here's protein C in a protein s they're circulating through the blood and then there's a protein on the blood vessel called thrombo modulin and what thrombo modulum will do is it'll activate protein C so now you have protein C and protein s and we're going to put like plus sign here this is an activated one and what this does is is this inhibits other particular clotting proteins that want to induce clots it inhibits Factor five and it inhibits factors eight so now if I inhibit these two factors I basically reduce the risk of forming a clot so the kind of concept here is I'm inhibiting clot formation so what's the overall kind of thought process behind this is I'm inhibiting clot formation now we get through a Warfarin in the mix you give Warfarin when you give Warfarin you're inhibiting the enzyme that helps to stimulate this process I'll decrease the production of this but I'll really decrease the production of this first whenever this decreases I have less protein C and protein s even if I have thrombomodulin I don't have the activation of this I don't inhibit factors five so this is actually a stimulating it's supposed to again inhibit these particular proteins from functioning but I can't inhibit them because I don't have an act I don't have these to get activated so if I don't have this to get activated I can't inhibit these particular proteins and so what happens is they remain stimulated if they remain stimulated they help to propagate a clot formation so you're probably like okay wait wait wait wait wait hold on hold on I gotta call you out on this I thought Warfarin was just supposed to stop Fallout formation that was the whole point of being an anticoagulant now it's causing clots what the heck is going on here this process is very transient very short-lived this usually happens in the first four to five days after taking Warfarin so four to five days generally after taking Warfare and then what happens is this starts to kick in and then you really start kind of preventing clot formation okay that's the underlying kind of process here so Warfarin does lead to the inhibition of these particular you know pro-coagulants which you'll get an anticoagulant effect out of it but in the early phase it does actually kind of cause a decrease in these anticoagulants and so you get a slight Pro coagulant effect but it's very very short-lived a couple days and so because of that if I do increase clot formation I lead to these thrombi forming right I may lead to like small thrombiforming and small vessels near my cutaneous circulation and that can cause skin necrosis and so one of the things that you want to remember is if I actually do cause some of these small little cutaneous vessels to kind of get clotted off because of the protein C and protein s and as a result I end up with a little bit of necrosis around that area this is very short-lived and we can actually prevent this the way that we prevent this is we do something called bridging okay we do something called bridging in other words I start the patient on heparin and then once I get them therapeutic so I'll put them on Heparin and I'll get them to a therapeutic point then what I'll do is I will kind of switch to warfarin so there may be a small period of time so what I'll do is I'll get them on hepra and I'll keep them kind of nice and anticoagulated and then once I got kind of nice and anticoagulated I'll add on Warfarin so there may be a small period of time where they're on both Warfarin and on Heparin but what I'm going to do is I'm going to titrate the Heparin down get my Warfarin nice and therapeutic but I'm going to have the Heparin give me the anticoagulant action for a couple days then after that four or five day period now protein C and protein s aren't the problem now which is these that I'm kind of dropping down and I'm actually going to get that anticoagulant effect and that'll kick in and that'll soothe right over so generally what we do is we start people off on kind of bridging them with Heparin for a couple days we'll put them on Warfarin we'll put them on Heparin kind of get them nice and therapeutic and then we'll take the Heparin off and then continue them on Warfarin for however long they need to be on it okay so that's the way that we can generally prevent Warfarin induced skin necrosis is by bridging them through the short Pro coagulant period due to the drop in protein C and protein s for a couple days and then they get the full anticoagulant effect afterwards after that kind of like Pro thrombotic state has occurred okay all right my friends that covers vitamin K antagonists let's move on to the last thing which is patient takes any one of these medications and they bleed what do we do if a patient is taking any of these medications yes there is a risk of bleeding sometimes this bleeding can be very minor it's very important to be able to differentiate between something and being very minor and something to be like life-threatening and severe so and again we'll go over kind of like the degree of which one has the most bleeding risk a little bit later but when we talk about these if a patient is taking whether it be an anti-platelet an anticoagulant or thrombolytic they can develop very minor characteristics of a bleed all right so what are some of those that you should be able to recognize I'd say look for like skin bleeding right so if a patient develops like little petechial lesions so little petechia lesions are one another one is like ecchymosis this is another one to watch out for um other things just maybe like prolonged bleeding so maybe they have like a wound or a cut and they're just bleeding from like that actual wound for a little bit longer time period so these are like minor things to watch out for okay um another one is going to be sometimes just like epistaxis so if they're bleeding from their nose so if they have epistaxis um or if they have any kind of like bleeding from their Ginge of us so gingival bleeding okay these are minor they're not going to exsanguinate from this epistaxis just be careful especially with posterior epistaxis if there's significant like splurging of blood back there that might move them over into like more of the modern severe type if it's getting pretty bad that you would actually consider reversing the drug so just be careful I would kind of add this one over here just with the kind of like the point of being cautious if it's posterior epistaxis that might get you over into like the more moderate and severe section and the reason why I'm kind of doing this is that if a patient develops a little like petite lesions or ecchymosis so they're just bleeding a little bit longer from their skin or they have like little anterior epistaxis or they have like a little bit of a gingival bleeding or they're bleeding a little bit from their uterus or they're having a little bit of a knee kind of like they're having like a a hemarthrosis those aren't indications where I'm going to reverse the drug it's really not it's more they're exsanguinating they're at risk of death that I would consider reversing the drug and I think that's a really important point to get so if it's a posterior epistaxis where they're really bleeding that might move them over that may transition them just to be cautious here this may kind of transition them over into moderate to severe just be careful of that okay same thing with uterine bleeding so if a patient's developing kind of like uterine bleeding this may be some degree of mild but again with the caveat here that if the bleeding becomes to the point where they're exsanguinating then this could potentially move them just being cautious here that it could be anywhere from mild but sometimes it may progress and just be careful it may cause a severe blood loss especially if they're like dropping more than a leader so if they're getting to the point where they're dropping like greater than about a liter of blood in a 24-hour period then that's a little bit more severe and that would kind of move them over into the moderate severe category last one is if they develop kind of like blood within their joint so they develop like a hemarthrosis hemarthrosis so these are the things that I'm talking about if a patient comes in they got mild like skin lesions like particular lesions ecchymosis prolonged bleeding time they have an anterior epistaxis they have mild uterine bleeding they have hemarthrosis those are things that you can kind of just keep and monitor the patient's drug levels make sure maybe see if you have to make any modifications to their drug levels okay maybe you got to hold a dose or something like that but if the patient comes in and they have a massive posterior epistaxis or a massive uterine bleeding where they're losing like a large flute like volume over kind of a 24-hour period that might put them over into this moderate severe category so watch out for posterior epistaxis and very significant uterine bleeding another thing is if they develop like a big old honking bleed in their brain so if they develop like an intracerebral Hemorrhage or subarachnoid hemorrhage these are also things to consider so watch out for things like you know intracranial hemorrhages watch out for things like subarachnoid hemorrhages or subdural hematomas things to that effect that are maybe related to their anticoagulation another one is if they're like bleeding into their git so they're like a a large like a GI bleed of some type whether that be kind of an upper GI bleed or a lower GI bleed obviously upper GI bleeds are going to be more brisk potentially and scarier but GI bleeds this can cause a pretty significant amount of blood loss so just think about that one as well um the other thing is that sometimes people can bleed into like behind their actual git so into What's called the retroperitoneum so watch out for this as well as well I'm going to kind of abbreviate this one our rph so retroperitoneal hemorrhages these are also things that you want to be careful of as well so the patient develops a brain bleed they help a GI bleed I believe behind their peritoneum the retroperitoneal bleed massive posterior epistaxis massive uterine bleeding or they develop bleed Within These cavities so a bleed within the peritoneum obviously it may be a g I believe believe within the retroperative retroperatinum blade what about blood within their pleural cavity they develop a massive hemothorax or within their pericardium a hemopericardium see these are also things that are life-threatening so hemothorax and then a hemo pericardium which increases the risk of the patient developing cardiac tamponade and this increases the risk of forming like maybe a tension pneumothorax of some type so I think these are things to think about so this these are severe situations super obvious right but if a patient is exsanguinating from a posterior pistachos or an abnormal uterine bleeding that's also concerning in these situations these they need reversal of the antiplatelet the anticoagulant or the thrombolytic and these scenarios not so much maybe just monitor the levels keep an eye on them see if they're too high if you have to make some dose adjustments or hold the dose a little bit no need for emergent or immediate reversal that is why this is important to differentiate okay now I've kind of been talking about this a little bit which is how do I really determine the levels of a drug right is what do I do today hey what's the level of that drug again oh yeah it's good all right cool no we gotta we have to have no specific tests right so I think one of the big things to think about here is what are some of the tests that I can utilize so one of the big ones here is what's called your PTT so we can monitor what's called your PTT now your PTT is your partial thromboplasting time and what I want to know is is if the PTT is way too high because that increases the risk of bleeding so that really looks at a couple different drugs but the most common one to be honest with you is going to be Heparin and it's really a specific type of Heparin this is really unfractionated Heparin that really kind of is based upon the PTT level so if you're trying to look to see what the PTT level is if a patient is taking unfractionated Heparin we like to monitor that PTT so checking the PTT is very helpful for this drug category another one is monitoring what's called your anti 10A level this isn't a common level to be honest with you but you can utilize it um and so what this looks at is it looks at anything that's kind of inhibiting the 10A whether it be indirectly or directly oh so you're like wouldn't Heparin on fractionated Heparin work it would I could technically do any heparin I could do all the heparins baby I could do unfractionated Heparin this could be low molecular weight Heparin this could even be Fonda paradox this could also be my 10 a Inhibitors so my River Rocks abandon picks a banded oxiban all of these could be monitored by my 10A levels Isn't that cool so you're probably like okay what about a thrombin level I only got one I mean you could do something called a thrombin time which may be potentially beneficial um if you really wanted to you could check something called a thrombin Time and a thrombin time would really specifically look at really only one drug and that is your What's called the bigotran but it's not the best test so oftentimes we don't really have true like reliable tests to really measure your thrombin Inhibitors so but the bigotran may be beneficial um other things you could consider um your our GATRA band and bivalaruden you could consider maybe even sometimes adding those into some of these other tests but really there's nothing great for those ones as well I see the ones that truly you would want to know for the test is PTT for unfractionated Heparin consider anti-xa level and specifically low molecular weight Heparin and then your 10A inhibitors thrombin time into bigotran or here's another really big one INR so INR is what's called your International normalized ratio and what it does is it looks at something called the PT so it's based off of your PT so it takes the the actual um time your Prothrombin time of you and then you divide it by the actual PT of the nearby patient population like the average of the PT around the patient population you're in and it gives you a ratio and that's called your INR and the INR is really really important for Warfarin I don't want you to remember a lot of numbers son of a gun I don't want you to remember a ton of numbers but I think that this is one that you could potentially get tested on in the exam and what we actually prefer is that because Warfarin has a very narrow therapeutic index I used this term before we really like the INR to appropriately be between two to three for most patients you may may increase the INR to approximately 2.5 to 3.5 if they have like a mechanical valve right so if they have like a mechanical valve you may increase that INR just a little bit more but for the most part that's the primary thing to think about okay so these are some of them other tests that you'd want to consider is that the patient is bleeding okay especially things like GI bleeds hemothorax posterior epistaxis uterine bleeding those that can cause a massive amount of blood loss so if you have a patient who is you know bleeding I think it's also reasonable to check and order some other tests so things that I would actually really consider checking here for a patient population is if I'm really worried especially with this is really more common with GI bleeds retroperitoneal hemorrhages massive posterior epistaxis and massive uterine bleeding okay I would check a CBC because the CBC could show me a low number of red blood cells it could show me a low number of platelets so this is something else that I would also consider checking now your pry leg anti-platelets do they have like any assay that we can like no not really so for anti-platelets there's nothing really specific I mean obviously monitor your platelet levels with anti-plates because you can potentially develop TTP but really no there's no specific like assay to really monitor the level of it aspirin or you know p2y12 receptor Blocker we had the one that determines the response to the drug but not a level of the drug okay so none really specifically for antiplates we talked about most for the anticoagulants Heparin the 10A Inhibitors not really anything specific for our gotcha Banner by valerudin and then INR for Warfarin so I think the most important ones is INR and PTT level these two if you have the brain space to remember them add them in and then if you really are concerned that the patient may be kind of bleeding a CBC to check the red count and then their platelet count is also kind of beneficial one more is I would also consider checking something called fibrinogen and fibrinogen is really kind of coming down to one specific drug and that's really TPA because if you think about it TPA does break down fibrin but it also breaks down fibrinogen so checking that with respect to a patient who's taking TPA and now they're developing bleeding symptoms that may be a potentially beneficial thing to check in combination with the factors for bleeding such as a low and a red cell count and a low platelet count okay one more thing that I want to talk about here guys when we talk about bleeding risk so let's put a hair just like a bleeding risk so risk of bleeding I think it's important to be able to kind of understand which ones are really the scary ones all right so obviously when you think about these aspirin is probably going to be on the lower end right and then I would say after that would be kind of like your P2 y12 you know receptor inhibitors then after that I would say you know these are probably going to have the higher ones so GP 2B 3A Inhibitors are also going to be these probably have a higher risk of bleeding so if we're going again this is the least amount then this one then this one then I would say you're going into any of the anticoagulants what I would say is I would say if you kind of had like your doax and your Heparin molecules those would actually probably have a lesser bleeding risk in comparison to Warfarin but the last one is going to be any thrombolytic so I think it's really important to understand that when a patient is taking these medications their bleeding risk could be dependent upon which one of these are on so as you go in this direction if you take these particular medications there is a higher bleeding risk just inherent to the actual drug category with Warfarin just having a higher bleeding risk than most of the other anticoagulants gp2b3a Inhibitors having a higher bleeding risk than all the other antiplatelets and thrombolytics having the highest bleeding risk out of compared to all the actual drug categories that's important okay my friends here's what I need us to Now do patient comes in they take one of these drugs they got mild bleeding on the skin mild nasal bleeding mild uterine bleeding you know maybe you got the Kmart throws it's not too bad we'll check these levels see if we can make any adjustments maybe hold the dose decrease the dose whatever or they come in can't breathe got a hemothorax don't have any blood pressure because they have hemopericardium they're losing blood out of both ends maybe out through their massive hematis or they're having massive GI bleeding out the other end uh end and they're or they're losing a lot of blood and they're hypotensive because they have retroperitoneal bleed or they can't move their entire right side because they have a big bleed on one of the sides of their brain in those situations we have to consider immediately reversing the drugs that potentially cause these problems because maybe they're at Super therapeutic levels and then checking the level accordingly may also be beneficial but I think the important thing is is if they have a high bleeding incidence moderate to severe in in that situation what medications could I use to reverse some of those drugs because this is a high yield let's talk about it I'm a friend so a patient who comes in they got some degree of like moderate to severe bleeding and it's secondary to the anti-platelet anticoagulant or the TPA you check the levels it confirms which one now you got to reverse the drug all right anti-platelets I really don't want to include this because um they honestly you should not reverse these but if a patient is taking any anti-platelet and they do develop massive bleeding you could consider I would highly recommend that you don't um there's a lot of evidence to really kind of go against it but I would say plus or minus something called desmopressin it may increase or improve the function of platelets that's it and I that's all we're going to say about that one and this would go for aspirin p2y12 receptor blockers gp2b3a Inhibitors all of those let's move on to the next thing so we go into the anticoagulants the first one that we mentioned was Heparin okay so with Heparin for this one it's actually going to be something called protamine sulfate so I do want you to remember that one because that's a high yield one so protamine sulfate is another one I've given this one a couple times um unfortunately and this is a pretty common one to give as well um not as common as the next one so you could do this so when we talk about protein sulfate it could be primarily if I'm actually going to write this here unfractionated Heparin way more common than it would be for low molecular weight heparin okay the next one is for your doax okay so this is for your doax but I'm actually what I really want to do here is actually more specifically I want to break them down into and the reason why is there's a there's a special reason here so you're 10 a inhibitor so riveroxabana pixabanadoxaban with these there is a special one out there um it's crazy expensive and to be honest it found no true difference in benefit from the actual classic drug that we give but for the River Rocks band of pixabanda doxiban um and dexinet Alpha but just get ready to break the actual bank and never be able to you know pay for your mortgage after this one the other situation here is if you don't have indexing at alpha or you don't want to pay the massive amount of quantities for this drug which is not any more Superior than this other one than in this other situation you can give something called four Factor PCC and all this means is it contains factors 2 Factor seven factor nine and Factor 10. so it's all these clotting proteins that are essential to actually helping to promote a clot especially in this case Factor 10. so it's pretty cool in that sense the other thing here is if we go into the next one so the thrombin Inhibitors the thrombin Inhibitors I want us to kind of also think about here with thrombin Inhibitors I actually just recently gave this one out and this is actually a high yield one so for this one it's called the bigotran so the bigotran is that one of the thrombin Inhibitors and this is that PO version for this one there is one particular drug heck of a stinking name it's called Ida rakizumab also known as praxbind this is one that you actually really should know because this is going to be the reversal agent for dabigatran if it's the other version so if it's the argatraband or if it's the um by valaruden by valaruden these ones you treat with four Factor PCC okay so again recapping please for love of goodness don't do this with anti-players don't get plated transfusions either but again sometimes they may even consider plus or minus platelet transfusion especially if they're going to be going to get like a neurosurgery so if they develop like a bleed sometimes I like to aim for a greater than 100K platelet levels so they may consider platelet transfusion or desmopressin Heparin protamine sulfate more advanced for unfractionated in comparison to low molecular weight 10A Inhibitors and dexane and Alpha if you don't want to be able to pay your mortgage and then four-factor PCC would be the alternative and a lot cheaper thrombin Inhibitors the bigger Trend you give either a kizumab and if it's the arcatra band and the bivalry in which the IV versions it's four Factor PCC okay Warfarin my friends we go into warfarin for Warfarin and this poppy here you give two particular drugs one is you give IV vitamin K so you give IV vitamin K and then the other thing that you also give is you give four Factor PCC you give this because again warfar inhibits the production of functional 27910 CNS so you'll actually give them two seven nine ten ten and then IV vitamin K will replenish the vitamin K that's being inhibited by Warfarin so that over a 24-hour period and forward you actually continue to make functional two seven nine ten CNS which is pretty cool if a patient is not like massively urgently bleeding but they're INR so another thing is that they're kind of a caveat here like a add-on here is that if the patient has a super super like high INR greater than their level of two to three or two point five to three point five they have a mechanical valve you can actually kind of look at that but no bleeding so in other words it's not an emergent indication for this then what you can do is you can give them po vitamin K and hold the dose of Warfarin for maybe a day or two and then keep checking their INR until it normalizes okay that's just a little add-on there the last one is TPA my friends so for TPA the reversal agent for this particular situation is you're going to give something called txa transamic acid okay tranexamic acid is actually going to work specifically to kind of inhibit the fibrinolysis so it's going to inhibit any further fibrinolysis but then the other problem here is that you need to give them fiber engine because TPA also can break down fibrinogen so I want to give them back some of the fibrinogen and so I can give them something called cryo precipitate cryoprecipitate and this is important remember I told you with TPA to monitor the patient's fibrinogen levels if the fibrinogen levels are like less than 150 I would consider giving them cryoprecipitate because guess what cry precipitate is cryoprecipitate is fibrinogen and so you're going to basically increase their fibrinogen the other thing is that with TPA it actually does break down the connections between the platelets so you may drop the plates a little bit so some patients you may even need to do a plate of the transfusion but this is really the Hallmark is txa plus or minus cryoprecipitate if they have a really low fiberinogen level my friends in this Behemoth of a video and this in Avengers Infinity war movie that we just went through we talked about so many drugs let's quickly and I mean quickly talk about some cases to cement this stuff in all right Engineers let's do some questions here so first one here which are the p2y12 ADP receptor antagonists reversibly binds this receptor so we didn't actually mention this within this three hour long Infinity war movie that we just talked about today but really quickly when we talk about the p2y12 receptor blockers all of them except for Ty kagrelor is reversible and so what why is that really important it really comes down to compliance so when a patient takes decagrelor if they decide don't want to take this medication anymore that's a problem because now they lose their complete antiplatelet effect because it's it's actually reversible as compared to Clopidogrel pursue girl to clopidine those are irreversible and so it's actually going to be somewhat more beneficial the patient decides to miss a couple doses they'll still get the anti-platelet effect a little bit so that's very important so the answer should be take Agri lore okay let's go to the next one we got a 70 year old woman diagnosed with non-valvular afib that's really important her past medical history is significant for chronic kidney disease and her renal function is moderately diminished which anticoagulant for atrial fibrillation avoids the need for renal dose adjustment in this patient well oftentimes I think it's important to remember that kind of any of the direct Factor Inhibitors have some degree of renal excretion and so because of that I would actually be very cautious putting patients on those medications such as a pixaband to bigotrano River oxiban because they are readily excreted um way much more so than Warfarin I would actually go ahead and stay away from those and particularly kind of confine myself to warfarin for this indication here unless you want to monitor their levels way more frequently such as utilizing like anti-10 a levels to monitor things like a pixie band River Rocks band but Warfarin would be kind of the go-to in that particular scenario 80 year old woman is taking Warfarin indefinitely for the prevention of DBT um compliant stable INR to nice bleeding bruising diagnosed with UTI prescribed bactrim to so sulfamethoxazole trimethopram um what are the expected effects on his Warfarin therapy well as we talked about before bactrim or trimethylonethoxazole is acyp450 inhibitor so whenever Warfarin is getting metabolized if you inhibit the metabolism of Warfarin you'll actually increase the efficacy or the concentration of the warfarin drug within the blood and so now you're going to have more Warfarin running around the blood you're going to have an increased anticoagulant activity of Warfarin and so you'll have a higher risk of bleeding in these situations so I would say it would be B increased anticoagulation effect of warfarin antidote for reversing deleting so a 47 year old woman came to the Ed severe bleeding upon evaluation um discover that she takes to bigotran okay for a history of multiple devotees what is the appropriate reversal agent to administer to the patient at this time well it's the name to fame is idricizumab so protamine is for Heparin vitamin K in addition to things like PCC or ffp can be given for things like um Warfarin hydrochism has particularly for the bigotran and so reverse agent does not exist for this medication that's not necessarily true so the bigotran we would give Hydra casimab as a monoclonal antibody as a reversal agent for that drug all right um which must happen Vine in order to hurt its anticoagulant effect um so generally a binds onto antithrombin 3 right so naturally Heparin is a part of our normal kind of molecule within the body so it's an endogenous molecule it's a Heparin sulfate right and it usually will bind antithrombin 3 and enhance the activity of antithrombin three wheelchair breakdown things like thrombin Factor 5 factor eight Etc so um in this situation here I would definitely say anti-thrombin 3 would be the primary one that it would actually be able to exert a santicoagulant effect via um fire and selective so which is considered fibrant selected because it rapidly activates plasminogen that is bound to fibrin so we talked about the kind of thrombolytics within the lecture of anticoagulants and I thought it was a good one to throw in there with them um and that this is going to be things that activate the plasminogen that helps to be able to convert it into plasma which breaks down fiber and that would be specifically things like auto place or tonight to place so any type of TPA molecule would be the best situation here so altar Place connect the place streptokinase those kinds of things so in this situation I would say it's primarily going to be all to place so a um a 56 year old man presents the Ed with complaints of swelling redness and pain in his right leg so diagnosed with a DBT a provider wants to start an oral agent okay which drug is the most appropriate for the treatment of DVT in this patient so River Rocks band is an oral agent uh but tricks have been does not really utilize really often it can be used prophylactically but not for acute DVT and to be honest with you I don't think I've ever used it or seen it in practice ever enoxaparin is a Heparin molecule primarily given via IV um and then uh Clopidogrel is not an anticoagulant it's an anti-platelet so and that would be best in this one so I'm kind of left with batrix abandon rivaroxaban is the primary two oral agents here um again this is not for a qdvt it's primarily purple axis and I don't think I've ever seen it utilized ever once so River Rocks event will be the correct answer this is a factor 10 a inhibitor and so is patrika band but again it's going to be riveroxy band for this answer here all right which is the most appropriate for reversing the anticoagulant effects of Heparin so protamine sulfate is going to be the primary answer here so again you can give vitamin K your vitamin K would be good in situations such as in Warfarin related which can give it kind of a good 24-hour control hopefully it'll help to activate some of those vitamin K epoxide reductase enzymes and help to kind of increase the synthesis of factor 2 7 9 10 protein C and S but generally Vitamin K is going to be for Warfarin txas for things like you know thrombolytics like TPA so altoplastonical Place protamine sulfate is going to be primarily again given for situations such as patients who have Heparin related bleeding so I would give protein sulfate um 62 year old man taking Warfarin for stroke prevention and afib presents to his PCP with an elevator 9rf 10.5 without bleeding so that's good um and is expected to hold his War for a dose given oral vitamin K generally should be given IV vitamin K but it doesn't matter given oral vitamin K which one of the what when would the effects of vitamin K and the iron most likely be noted on this patient so I already said that kind of 24 hours so you can give things like um a PCC so we call that the prothrombin complex concentrate we can also give things like ffp but those will help to replenish directly factors 27910 protein CNS but um you know generally vitamin K will be something that over a 24 hour period will help you to continue to synthesize more of those factors such as Factor two silver nine ten protein C and S so I'd say 24 hours for vitamin K immediate effect from things like PCC or ffp a 58 year old one man receives an intravenous ultiplace treatment for acute stroke five minutes following the L to place infusion he develops angiodymium I've actually seen this once um it's very interesting um generally you give them steroids and antihistamines and just be careful watching their Airway but which of the following drugs may have increased the risk of developing angioedema in this patient and that would be an example these Inhibitors naturally have that ability to increase the Brady kind of production by inhibiting the breakdown of bradykinin so they end up they end up causing higher levels of protein and causing vasodilation increased capillary permeability and swelling of the upper Airway structures which can definitely be precipitated whenever a patient gets TPA related infusion for a stroke it actually has a double kind of Whammy effect but you can see this and it's kind of frightening sometimes when you see but it'll be a nice inhibitor all right my friends that will cover all of the questions that you guys need to know about anticoagulants and thrombolytics I hope it made sense I really do I hope that you guys enjoyed it thanks for sticking in there thanks for watching the video thank you for being so supportive of us and Engineers love you thank you and as always until next time [Music]

Channel: Ninja Nerd

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Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science

Id: aSRI6BGXX70

Length: 190min 39sec (11439 seconds)

Published: Fri Nov 25 2022