Primary Hemostasis | Physiology, Pathophysiology, and Pharmacology

Hi everyone, Dr. Mike here. In this. video, we're taking a look at the. process of primary hemoasis. This is the. first step involved in stopping us from. bleeding out. Now, there's two steps in. hemoistas. There's primary hemoasis and. secondary hemoasis. I've done a video on. secondary hemoasis, also known as the. clotting cascade. I suggest you watch. after this video. But let's take a look. at primary hemoasis. So to begin, let's orientate ourselves.

We have a number of busted up blood. vessels here and I've got some titles to. them cuz in primary heistasis, there's a. couple of different stages, right? The. very first stage is called vasoc. constriction. We're going to talk about. that first. Then the second stage is. platelet adhesion. The third stage, which we're going to look at in two. parts, is platelet activation. We're. going to look at in part A and part B. And then we're going to take a look at. the final stage which is platelet. aggregation. Effectively by the end of. all this, so by the end of platelet. aggregation, we should have formed what.

we call a platelet plug. Not a clot, but. a plug. That's important because what. we're going to talk about in this video. is some of the disorders that can occur. that result in platelet problems and. bleeding issues, but also some of the. drugs that can be used to address. different stages to help people from or. prevent them from clotting. We'll get. there. Okay, let's begin with vasoc. constriction. So, you've got damage to a. blood vessel. You don't want to bleed.

out. The very first thing that happens. is a uh vaso spasm. So the blood vessel. constricts to limit the blood moving. past. How does this happen? Well, you've. got what we can see here lining the. inside of the blood vessels. We've got. endothelial cells. So these are the. epithelia of the red blood cell. Now. these endothelial cells when they die. and they burst open like this, they can. release chemicals. And one important. chemical they release is one called. endoththellin.

one. And endothelan one is a potent. vasoc constrictor. So it will tell this. blood vessel to constrict. Now when it. tells this blood vessel to constrict. obviously it's narrowing limiting the. amount of blood going past. Great. It's. not going to stop bleeding but it's. going to help us in the early stages of. limit bleeding out. Then the next step. platelet adhesion. So now we have to. bring the platelets into play. Now an. important point here is that we have all. these endothelial cells right endothelia.

like I said are epithelia and all. epithelia which line our body they sit. upon a basement membrane. Basically what. I'm saying is these cells sit upon. connective tissue such as collagen. So. when they're damaged collagen is exposed. right? So you're going to have all this. exposed collagen. Now collagen is a protein. It's mostly. negatively charged. That's also an. important point to highlight. These. epithelial cells also produce something.

important. The thing that it produces is. called von. willibbrand. factor. and we'll be writing that up as VWF. [Music]. So these cells endothelial cells produce. von willilibbrand factor and they will. bind to the collagen. So let's label the. collagen just so we can see what's going. on. So we've got the collagen and we're. going to have von willibbrand factor. connected to it. VWF.

and let's do one here as well. We got a. von willibbrand factor here. Brilliant. Now we haven't even introduced a. platelet yet. So what the platelets will. be doing is the platelets actually as. they enter the blood this particular. area of the blood vessel they actually. will roll down or along the blood vessel. wall until they get to the exposed. collagen and vonilibbrand factor. And. what platelets have.

brilliantly are receptors. for vonilibbrand factor. So let's draw. another one up here. So here's a. platelet. So let's write platelet so you know what. it is. And it's got a receptor for von. willilibbrand factor. This receptor is a. GP protein receptor. And so it's called. GP for G-proin. 1B. G-proin 1B. That's the name. It's. important because we'll talk about a. disease that affects GP1B. So now we've.

got is the platelets have adhered to the. site. That's all that's happened. Platelets have adhered. All right. Brilliant. What's the next step? Well, now we need to activate these platelets. So once that platelet is bound, some important things happen. Simultaneously, secondary hemoasis is happening. So. secondary hemoasis triggered by the. damaged blood vessel triggers the. clotting cascade. Now after you go. through all those various factors, a.

really important uh product is produced. called thrombin. Okay? and throbbin's. going to start this platelet activation. So, let's just draw up our collagen. again. Let's draw up the vonilibbrand. factor. There's our vonilibbrand factor. We've. got our platelet. with its GB1B receptor on it, right? And it's bound to it. Now what. happens is that thromben is produced and.

thromben will bind to a thromben. receptor. So there's now going to be. another receptor on this platelet and. this is a thromben receptor. So here's thromben. Brilliant. Now thromben is bound to a. receptor that's called P A R1. So this. is a protease activated receptor 1.

Thromben binds to it. This triggers an. intracellular reaction, right? That. causes the granules. Now remember. platelets have granules. Triggers the granules. to be released from the platelet. Now. what's in these granules? Well, a couple. of important things, adenazine diphosphate, ADP,

serotonin, and more von willibbrand factor. Now, there's other things there's like growth. factors and platelet activating factors. and calcium, but these are some very. important ones. So, these are in the. granules that are being released due to. the binding of thromben via the P1. receptor. Now a couple of things. Serotonin is actually. another. vasa constrictor. So it further helps. constrict that blood vessel. So that's.

good. Von willilibbrand factor. That's. great. More of it can travel down. and bind to the collagen to help more. platelets bind. Brilliant. What does ADP. do? Okay. So ADP will and now we're. going to go to part B. ADP will bind to. ADP receptors back on the platelet. That's interesting. So, let's draw this. up again. Collagen. von willilibbrand factor.

platelet. And now we're going to have the ADP. binding. to an ADP. receptor. Remember we also had thromben. bound, right? So let's draw up the bound. thromben as well cuz that's going to be. important. So let's drop the bound.

thromben. And we said that the thrombin is bound. by P1. The ADP is bound by a P2Y12. receptor. Now, the reason why I'm. telling you this, I don't often say. receptors, is because they're actually. important when it comes to some drugs. All right? So, when both thromben and. ADP bind, they stimulate activation, which is part of this process and then.

leads to the next step of this. particular platelet. Now, one of the. things that it does is it triggers again. it's triggering intracellular processes. and one of those processes is to tell an. enzyme called COX one to trigger the. production and release of something. called thromboxane. Thromboxane. Thromboxane. A2. Cox. Now I Yeah. Cox one triggers.

thromboxane A2. Thromboxane A2 will bind. back to thromboxane receptors and. further trigger activation. So what are. the three things that trigger. activation? Right? Three things that. trigger activation is thromben is a big. one. ADP is a big one. and thromboxane. is a big one and I haven't even said. what activ what this activation really. is right so there are three triggers to.

trigger this activation now thromboxane. importantly. thromboxane A2. also triggers vasa constriction so again. it's all sort of feeding in upon each. other now what ends up happening here is. that part of this activation is that. This changes its shape. The platelet. changes its shape because of thromben. binding, ADP binding, and thromboxane. binding.

Right? It changes its shape. So, we're. going to draw that up with it because. it's part of platelet aggregation. So, let's have a look again. We've got the. collagen present. We're going to have. the. vonilibbrand factor, right? We're going to have the. binding through that GB1B. and now the platelet has been activated. by thromben AB ADP thromboxane and now. it becomes spiky.

So these little arms or legs so are. called pseudo pods. Pseudo pods meaning fake arms but it. makes it sticky. It also starts to tell. receptors inside to come to the surface. So more receptors, right? And these. receptors are called again terrible. names GP. 2B and 3A. GB 2B and 3A. And what they do, so I.

said thromben comes in from the clotting. cascade. That's one product. Another one. is going to be fibbrinogen. So. fibbrinogen comes in and that's going to. bind. to GP 2B and 3A. So that's. fibbrin. oen. Right? Now what happens is that you're. going to have more platelets come in. that are getting activated. Right? More. platelet they get activated. So they.

become pseudopotic. they have their arms. coming out which means they also have. those receptors which then allow for the. fibrinogen. to bind. So now you've got so again this. is going to have another receptor on it. a GP 2B3A and you're going to have the. fibbrinogen bind to it which means. another platelet can come along get. activated right and bind to it. So now. we're forming a plug. All these.

platelets are coming along and forming a. plug because of the GP2B3A. receptor after it's been activated. So, we've got all these processes happening. Now, I don't usually go into this much. detail with things, but it's important. because there are some very important. diseases and disorders that can happen. Three important disorders of platelet. aggregation that are associated with. primary hemoasis. What are they? Well, two of them are associated with platelet. adhesion. So these two are called.

actually I'll write it here. von. willibbrand. disease. This results in a disorder of. vonilibbrand factor. So you have a. genetic disorder which does not allow. for vonilibbrand factor to be produced. What does that mean? That means you will. not have platelet adhesion. So this the. start of this whole process can't occur.

So you have a problem with forming a. platelet plug and platelets adhering. Another one is called. Bernard. Solier. syndrome. and Bernard Solier syndrome is a problem. with. GP1B. Right? So von willilibbrand factor. that's a problem with.

unsurprisingly von willilibbrand factor. and bernard sol syndrome is a problem. with GP1B. So again both are platelet. adhesion resulting in pretty much the. same issue. The platelet will not bind. to the collagen. Right? So that's two. A. third one is called glman thrombbo. thrombocthenia and that is a problem. here. So this is an issue with the GP2B. and 3A. Right? So what we end up having.

here in this particular process is if. you have a problem here, you can get. Glasman. thrombusthenia, right? and that results in a problem. with this particular receptor. So that. means the fibrogen can't form bridges. between platelets and it can't form a. platelet plug coming in. So now we've.

got these three disorders and that is a. platelet aggregation issue. Now what. about drugs? Okay, so there are some. important drugs that are on the market. So one drug called clitigil. clopidigril. is an antagonist of the pt uh the p2. y12. Let's see if I can spell the drug. You know I'm not good at this. Clapidogil. So clipidigril inhibits P2Y12. So that.

means if you inhibit the ADP from. binding, which is what this will do, it. inhibits the activation of the platelet. So reduces platelet um activation. reducing platelet aggregation. So this. might be given to individuals in which. you don't want their platelets to. aggregate. There is also another drug. which affects the GP 2B3A as well. So. obviously not an inherited disorder but. this is a drug which has a tricky name. which is E P T I F I B A T I D E.

Epifiide. epifetitide. epifetide. epifitide. something like that. I'm sure it. inhibits GP2B3A. Brilliant. Now the final one which. you're all aware of is going to be one. that inhibits thromboxane. H what's that? Well, that's going to be.

our NSAIDs. Aspirin, because what it actually inhibits is COX. one, right? Aspirin, for example, ibuprofen, right? These are just some examples of. drugs that inhibit thrombox and again. reducing the platelet aggregation and. activation. So, this is primary. heistasis. I'm Dr. Mike and I hope that. helps. Hi everyone, Dr. Mike here. If you. enjoyed this video, please hit like and. subscribe. We've got hundreds of others. just like this. If you want to contact.

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