Hemostasis: Introduction and Examples

00:00 Welcome. Welcome to the wonderful world of thrombosis and hemorrhage. Kind of flipsides of the coin and both of which are incredibly important when we think about pathology in the human body. This first session is just going to be an overview to kind of give you a sense of where we're going and, as if we didn't already know it, why this is an important topic to go through. So, what you're seeing on your slide here is the fact that this stuff can kill you. I'm sure you are already abundantly aware of that, but it's not just bleeding that can kill you but also thrombosis, inappropriate thrombosis. So, what you're seeing on the left hand side is a heart that's been opened and the left ventricle is identified as the LV and the arrow is pointing to a mural thrombus, a blood clot that's in the chamber of the heart. What is on the echo below that? Again, with the arrow pointing to it is indicating that thrombus at the apex of the heart. Not only is that thrombus impacting blood flow through that chamber, but it's also a very likely nidus for embolizing, for going some place else. And if you're in the left ventricle as a thrombus, you're going to go out the aorta and the next stop is going to be your brain or a coronary artery or a renal artery or a big vessel in the leg and you're going to end up with infarction in those tissues. So thrombosis is that on a couple grounds. On the right hand side were showing us a CT image of a patient who has got multiple hemorrhages within the brain. Clearly, these white areas are indicative of significant bleeding that's going to have a significant impact on brain because there's no place for the brain to go. As you get more and more bleeding in this enclosure of the skull, you're going to be forcing the brain to squeeze out true things like the foramen magnum.

02:07 And this is going to be a cause of death. Now with that, the bleeding there is going to have areas of infarction in the brain that will not be functioning more. This is stroke or a cerebrovascular accident. So clearly, this stuff can kill you. As if you didn't need anything else to convince you, take a look here. So these are the causes, the 10 major causes of death in the United States. Numbers have not changed even in the brand new decade, in the 2020s. What you're seeing is that heart disease is a major killer, number 1 on the hit parade and that heart disease reflects valvular disease and myocardial disease.

02:53 Predominantly in this category is myocardial infarction, heart attack causing death and heart attack occurs as a combination of atherosclerosis that we'll talk about in a session yet to come. But also because of acute thrombosis, blood clot within the coronary artery is causing myocardial infarct. And then number 5 on the parade is stroke, cerebrovascular accident, bleeding into the brain or thrombosis, embolization of a blood clot into the vessels of the brain. So between number 1 and number 5, it's very easy to say that cerebrovascular and cardiovascular thrombosis and hemorrhage is a major cause of mortality not only in the United States but around the world. So, when we talk about normal hemostasis or stopping of the blood flow, hemostasis, we are really talking about having coagulation occur when a blood vessel is injured. Think about it. The rest of the time we want blood to flow in a nice liquid form throughout the body, delivering oxygen, removing carbon dioxide, delivering nutrients, etc. So, we don't want to stop it until there is injury. And then there's injury we wanted to be stopped at that point. We don't want to bleed to death. Conversely, we want to also have control mechanisms that ensure that even if we're forming a thrombus, we're only forming it at that site. So in other words, if I cut my finger I don't want to bleed to death because I have not stopped the bleeding. At the same time, I'm stopping the bleeding in my finger I don't want thrombosis to be involving my entire arm. So I need to have regulatory components that drive the thrombosis in the appropriate location. Okay, so some terms that you should know. So thrombus or thrombosis is the in situ, meaning in the human body, formation of a blood clot. Simple. It can be physiologic such as when you cut yourself or it can be pathologic, forming clots inappropriately even if there's no damage.

05:09 Okay, so good and bad. An embolus or embolism is a migration of a thrombus from one site to another. So, if I am at bed rest for long long periods of time, not moving my legs I can form a deep venous thrombosis, a DVT that can then, when I get up and walk around, break off and go to my lungs. That would be a pulmonary embolus. So it's a migration of a thrombus or even other materials within the vasculature. You can have fat embolization that occurs when you break bones during cardiopulmonary resuscitation or break long bones if you're in a motor vehicle accident and that material can also embolize, so it's not just blood clot.

05:52 Other things can be an embolus. There are times that we don't know, we can't definitively say whether something formed in situ, a thrombus that formed at a site, or whether it got there because it embolize from some other place. When we can't tell, we call it a thromboembolus, it's just the pathologist's way of fudging a little bit so thromboembolism.

06:18 Other terms that you should know. So petechiae are little tiny 1-2 mm hemorrhages. That is indicative of either defective platelets, platelets not working appropriately, or inadequate platelets or just intrinsic vascular fragility. And there are a number of collagen vascular diseases where that occurs, but they are little teeny tiny hemorrhages. You can have slightly larger hemorrhages that we call purpura. These are 3-5 mm in size and they're indicative of either platelet dysfunction, inadequate platelets, vessel injury, inflammation or trauma. So, the differential expands a little bit with purpura. And then we have the larger ones that everyone recognizes and these are ecchymoses, singular ecchymosis.

07:06 These are 1-2 cm hemorrhages and they can either be abnormal coagulation involving either platelets or coagulation factors or can be due to trauma and the ones that most of us are familiar with it's because you've been punched by somebody and you had some bleeding. This is the very typical bruise. The road map that we'll be following for the next few sessions is shown here. So we'll talk about normal hemostasis. We have to start at the beginning. How do we normally maintain liquid blood and then how do we get clotting or thrombus formation at a site of injury? After that, how do we break down that thrombus? Clearly, we can't leave that lying around. There's blood that needs to flow through that area so we need to break down the thrombus and the regulation of that. Once we've kind of understood normal hemostasis and thrombolysis, the breakdown of a thrombus, we'll talk about how we measure all the various parameters. You will use this day in and day out on the words so you'll need to know about partial thromboplastin time or prothrombin time, PTT and PT. We'll talk about that. We'll talk about specifically bleeding disorders, things that will lead to hemorrhage. We'll talk about things on the flipside of the coin, thrombotic disorders when patients are hypercoagulable or they have thrombophilia, they love the thrombus. Thrombotic disorders can also be just as devastating. And then finally, we'll talk about therapies. And we have many many many ways to interact with the components of the coagulation system simply because there are so many players as we'll see in these subsequent sessions. So with that, that's the game plan for where we're going, that's kind of some general terms that we all now understand and I look forward to seeing you in the next session.