[SOUND] [BLANK_AUDIO] The Direct-Thrombin inhibitors work on clot-bound thrombin, and that is the holy grail. To actually get the clot to stop growing and to allow the body to break it down. It prevents the activation of both free thrombin in the blood as well as the clot-bound from thrombin. And it also prevents the activation of platelets by thrombin.
Remember one of the main platelet activators is thrombin. So if you have an anti-thrombin, then that helps prevent more platelets from clumping together, and therefore helps with the clot situation. If you have a new clot forming on a tool in the brain or anywhere else that you're using intravascularly, such as coiling an aneurysm, or a catheter, or a guidewire, that's almost always going to be platelets. You want
to stop thrombin from from activating platelets and you want to use an antiplatelet agent such as Reopro to get rid of that. Heparin does not treat those very well. The antiplatelets work like magic. So here is the situation with all our antiplatelets, and heparins, and how they work, and what dose we use. This is very confusing. It's hard to understand.
You need to spend some time studying this because this is a very important subject, and it really can make a difference in your patient and clinical outcomes. This is an important concept. Also, how do you reverse heparin that you've given? At the end of the case, they have gotten 10,000 units over a period of a couple of hours. How much protamine do you give them? We know that protamine is a
drug that can reverse heparin, but how much of it do you give? You don't wanna give too much. Protamine itself can have side effects. You can be allergic to protamine because protamine is used in insulin. So you have to be aware of that, but you also don't wanna give too much of it and change the coagulation cascade. So how do you calculate how much protamine to
give? Well, the first thing you need to realize is that heparin has a half-life of about one hour, maybe 50 minutes, maybe 70 minutes, something like that. But let's focus on the one hour cause that allows us to calculate how much heparin is on-board, and that's the key. You need to know how much you're treating not how much you gave. You need to know how much heparin is actually still in your body.
So you have to calculate how much is on-board, and this is how to do it. Let's say you gave 5000 units of heparin at 9 AM. Well that means at 10 AM there's 2500 units left, at 11 AM, there's 1250, and at noon there's only 625 left. Let's say you gave another 3000 bolus at 10 AM, so that means at 11 AM you got 1500 units,
at noon you have 750, you gave another 3000 at 11 AM. So the total of all this is 625 + 750 + 1500 from the last bolus, which means you've got about 2900 units of heparin that's still on-board. You wanna reverse that. Remember that 10 milligrams versus 1000 units of heparin. So in this particular case if you reverse with 20 milligrams of
protamine that'd get rid of about 2000 units of heparin leaving 900 units of heparin. 900 units of heparin is homeopathic, doesn't do anything. So I would give about 20 milligrams of protamine in this situation to get the dose down to where you're not gonna have bleeding, you're not gonna have trouble with any sheath that you pull, and you're not gonna have any problem with bleeding in
your brain, for instance, and you've reversed all the effects of heparin down to a normal level. Another practical point is, how do you stop oozing around a puncture site? This happens to us
basically exactly the same thing. Heparin itself is just a large
group of various sized molecules all in this realm here. They cover this whole big spectrum. And what you get with low molecular-weight heparin is you get a bunch of these various things. All that are clumped down here on this low end of the spectrum of the heparin group. These tend to have slightly different effects because they
have a slightly stronger anti-Xa effect than the overall group of heparins. It's the large molecule heparins that are detected with the standard ACT test. So we can't really test easily in the lab unless you are testing anti-Xa to find out how the low-molecular weight heparins are working. But the key thing to remember is they're all heparins The good thing about low molecular-weight
heparin such as Lovenox is that it has a predictable pharmacokinetic profile. You can give standard doses, you can't measure the effects very well, that's good, because then you can use standard doses, but you don't have to measure it like you do with regular heparins. And it has very good effect on thrombin generation. But it still doesn't have effect on clot-bound thrombin, and that's
the same thing with any other heparins. It has a long plasma half-life cause it's not cleared from the blood as quickly as the large molecules are. It's difficult to monitor its effect, but it is possible to reverse it to some degree. And it's the same thing, you use protamine, the trouble is you can't really measure the ACT, you can't really measure the PTT. So you're gonna have to be reversing something
that you don't really know so you're just gonna have to guess. But you can use some protamine depending on what effect you think they've got, and just guess to reverse it. It does work to some degree. The special considerations for low molecular-weight heparin is it cannot be used to treat HIT. Heparin-induced thrombocytopenia because, Lovenox low molecular-weight heparin is heparin. So
it'll just make it worse. It is less likely then regular heparin to actually cause HIT, but HIT is very common. Low molecular-weight heparin have a very long half-life, so therefore they just kinda have to wear off as opposed to regular heparin which you can reverse in minutes. But remember you can get protamine with these and reverse these to a pretty good degree just right
off the bat. But you just have to kinda guess on what the proper dose is on that. But for instance, if you gave 5000 units of heparin and an hour later you give 20 milligrams of protamine, you can kinda do the same thing with the Lovenox. Just give 20 milligrams of protamine and it'll reverse the action of it fairly well. HIT is another subject that you need to know about, and the reason you need
to know about is because it's common. It's actually an allergic
reaction. It is prothrombotic. It's not thrombocytopenia just because your platelets go away, what happens is your platelets begin to stick to each other, and they turn into microemboli. So it's a multi-embolic thrombotic situation where everything is clotting in your body, and paradoxically, it looks like you have no platelets.
Well you do. It's just that the platelets are all sticking to each other. They clog up all the various arteries and arterials, and you get thrombocytopenia secondarily. It's essentially a severe drug reaction. We miss it all the time. We have patients that seem to be clotting, we give them more heparin, it doesn't work, we give them more heparin, it doesn't work, and then we're in a mess,
because we've made their allergic reaction even worse cause we keep giving this to them. We cannot treat this with more heparin. We cannot treat this with more Lovenox. What we have to do is give them a direct thrombin inhibitor such as the bivalirudin, lepirudin, hirudin, dabigatran. On the table during a case, the bivalirudin is very good to use, it's
quick, it's to the point, it actually acts as an antithrombotic with these things. And lepirudin has a much longer half life, but it'll get the job done too because these patients are in big trouble, frequently. So good luck with all of the treatment of the patients who we we're talking about here. This is a difficult subject, there's
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