Anticoagulation and thrombolysis

Voiceover: Okay, so here we have a blood vessel and it's been injured. So right now I want to do an overview of hemostasis first. We want to make sure when an blood vessel's been injured, that the blood that's flowing through that blood vessel continues to flow through the blood vessel, and we try to minimize as much as possible, the amount of blood that leaks out of the blood vessel at that site of an injury. And the way we do that is through hemostasis. And the first part of hemostasis is making that platelet plug. And this happens during primary hemostasis. But it's still kind of weak, so we need to make it stronger. And the way we make it stronger is through secondary hemostasis. And what we do is we get this protein called fibrin. And we link it up together and we create this fibrin mesh over the platelet plug. And this fibrin mesh over the platelet plug is what we call a clot. Now, what were to happen if hemostasis were to continue and nothing were to stop it? So we'd just get clot after clot after clot after clot. So you can see that that's a problem. Now the blood that should be flowing through is getting backed up behind this clot and not getting to where it needs to go. So even though hemostasis is good, if we have too much clotting, then that can be bad. So our bodies need a way to make sure we don't get many clots. So let me get rid of these clots. And the way that our bodies do this is through two processes, called anticoagulation, and thrombolysis. Anticoagulation is the process that prevents any clots from forming. And thrombolysis is the process that breaks down clots after they've been formed. And these two processes are what I'm gonna focus on today. And this tug-of-war between two competing processes happens a lot in our body. Our bodies like to maintain a certain equilibrium. A middle ground, a set point, we have a normal. On a day to day basis, our bodies need ways to get back to normal. Let's take body temperature, for example. Our bodies like to stay at 98.6 degrees Fahrenheit, which is about 37 degrees Celsius. So that's normal, that's where we like to be at. Of course it's a range, so it can be a little bit higher, a little bit lower, but nothing too drastic. But sometimes we can get lower than that and we can be too cold. Say it's snowing outside and you don't have a sweater. And so what our bodies do in order to get our temperature back up, is we shiver. Our muscles create heat to get our bodies back up to the temperature that we like. Or sometimes our bodies can get too hot. Say we have a fever, or sick, or or maybe we're running on a hot day. And what our bodies do in order to cool ourselves off and get our temperature back down, is we start sweating. And that cools us off, and that lets off the extra heat that we have in our body, and that gets us back to normal. So let me erase this now. And let me show you how this is similar to what's going on in our blood vessels. So our sub-point, our middle ground, let's say good blood flow. And this is important because if we have good blood flow, then all our tissues are getting what they need. They're getting oxygen and nutrients that's carried in our blood. But sometimes we can have some injury to that blood vessel, and then we'll start bleeding. And that goes away from what we want, which is good blood flow. And so what we do in response to that to get us back to having good blood flow, is we go through hemostasis. And that allows us to make a clot, stop the bleeding at that injured blood vessel, and get us back to having good blood flow. But if we have too much hemostasis or any other process that causes us to clot, we have too much clotting, then as we saw before, the clots can block the blood flow going through that blood vessel. So the way that we take care of that is through anticoagulation and thrombolysis. And with anticoagulation and thrombolysis, we'll break down any clot and prevent more clots from happening, and make sure that we have good blood flow in our blood vessel. So this is the balance between hemostasis and anticoagulation and thrombolysis. Let's go over exactly what our bodies do in order to prevent any clots or break down clots. So let's talk about anticoagulation first. In anticoagulation we want to prevent any clots from forming. So we want to prevent hemostasis. And in hemostasis we can prevent the platelet plug, or we can prevent making the fibrin mesh. So let's talk about making the platelet plug first, and how we prevent primary hemostasis. So here we have our platelets that are floating around in our blood. So we want to make sure we prevent clots from happening. There's no injured endothelial cells, so we don't need hemostasis to happen, we don't need platelets to get there. So our healthy endothelial cells will secrete two molecules. They both do the same thing. The first thing that they do is that they do prevent platelets from getting to the endothelial cells, from sticking to them. So they kind of block the platelets from getting close. And the other thing that they do is they act on the smooth muscle cells of the blood vessel, and they cause vasodilation. And that's important because we want to make sure that our blood vessels stay open and blood is able to flow through smoothly. These two molecules are called, one of them is called prostacyclin, and this is a peptide. And the other one is a chemical called nitric oxide. So now let's talk about secondary hemostasis and how we prevent that. In secondary hemostasis, let me scroll over, we make the fibrin mesh to make that platelet plug stronger. Which again, in this case we don't need because there's no injury, and so we don't need to make the clot. And the way we make that fibrin mesh is we activate the coagulation cascade. So here we have our clotting factors, the family of proteins. And ultimately when we activate the coagulation cascade, what we'll end up with is getting thrombin. The fibrin linking up on top of the platelet plug is what creates that fibrin mesh and makes the platelet plug stronger. So the way that our bodies, our blood vessels prevent secondary hemostasis is through two different molecules so that endothelial cells, the same cells that are lining the inner wall of the blood vessels, and these are the same cells that are making prostacyclin and nitric oxide, what we just talked about. It makes two molecules. One of them is called heparin-like molecule. And this molecule is on the surface of the endothelial cell, communicating with the blood. And what this molecule does is, it interacts with another protein that's already floating around in our blood. This protein is called anti-thrombin III. So you can see, in hemostasis we have thrombin and we want to make a clot. And now in anticoagulation, we have anti-thrombin III, and we want to prevent a clot. So what will happen is anti-thrombin III will interact with this heparin-like molecule. And when anti-thrombin III interacts with heparin-like molecule, what it'll do is it'll inactivate thrombin. So it'll prevent thrombin from making fibrin from fibrinogen, and it will also inactivate a coagulation factor, coagulation factor X. And the second molecule that our endothelial cells have on the surface of their cells that's communicating with the blood, is a protein called thrombomodulin. "Thrombo," again, means clot, and "modulin" is modulate. So, to change or alter. So we said thrombin is what gets fibrin from fibrinogen. But what thrombomodulin will do is if there's thrombin floating around in our blood and we want to make sure that we don't clot too much, is it'll get thrombin and it'll change what thrombin actually normally does, which is make a clot. So that it is actually working in anticoagulation. But it's not just thrombin and thrombomodulin that works in anticoagulation. When we have thrombin and thrombomodulin working together and interacting with each other, then now protein C, with the help of protein S will get activated. And once it's activated, It'll interact with the thrombin/thrombomodulin complex. Those three things help with anticoagulation. The way that it helps with anticoagulation is that it inactivates two specific coagulation factors. Coagulation factor V, and inhibits coagulation factor VIII. So now that we've covered anticoagulation, let's talk a little more now about thrombolysis. So like I said in thrombolysis we're breaking down the clot that we already made. So the way that we're able to break down that clot is with this protein called plasmin. I like to think of it as, like a little shark floating around waiting to break down those clots. So I'm gonna draw it like this, like a little saw. And this protein is called plasmin. And what plasmin will do is it will break down fibrin and fibrinogen. But plasmin isn't floating around in our blood all the time, or else we wouldn't be able to clot at all, because plasmin would be breaking down fibrin and fibrinogen all the time. So we want to make sure that we can have plasmin whenever we need it. And we need plasmin whenever we don't want to make a clot or whenever we don't need to make a clot. And so we get plasmin from plasminogen. And just like fibrinogen, plasminogen is made with just an extra piece of protein. And the way we get plasmin from plasminogen is through our healthy endothelial cells again. Our endothelial cells will release and secrete plasminogen activator. And this tissue plasminogen activator will take off that extra piece of protein from plasminogen and make plasmin. So now let's zoom out and take a look at the entire picture of how anticoagulation and thrombolysis works.