Haemostasis

Hello. My name’s Professor Jon Gibbins, and in this session, I’d like to introduce to you a process known as haemostasis. Now haemostasis is the scientific expression that’s used to describe something that we all rely on. In fact, if we didn’t have haemostasis working in our blood vessels, we’d be at serious risk of bleeding following minor injuries. Haemostasis is actually the process that stops you bleeding. It’s a complex process that uses a number of different biological systems. Now clearly, it’s really important that if we injure ourselves - and this could be quite minor injuries all the way up to relatively major injuries - that our circulatory system is able to prevent you losing blood quickly.

The speed of the response is absolutely essential. And therefore, we have developed systems that enable us to respond exceptionally quickly and effectively to this trauma. The problem with this, though, is that these very reactive responses are also prone to going wrong. And it’s these responses that underlie many of the cardiovascular problems that you’ve been learning about within this particular programme. Now the haemostasis system uses a number of different components within the blood. And we’re going to focus on two of these main processes. But broadly speaking, there’s a series of events that occur when injuries happen. First of all, blood vessels tend to constrict.

And this is important because this reduces the flow of blood and therefore reduces the potential loss through that site of injury. But the second, and perhaps most reactive part to this response, is due to some cells - and they’re blood cells known as platelets that circulate in your blood all of the time, surveying the inside of your blood vessels for damage - and when they encounter injury, they’re able to respond exceptionally quickly, clump together, and plug the hole. So platelets form a front line of defence. The other process, which is of equal importance, is known as coagulation.

And this is where your liquid blood converts from flowing liquid, liquid that contains cells, of course, as well - and this flowing liquid converts to a gel-like substance. And this literally plugs the hole and prevents the further loss of blood. So a concept I’d like to introduce you to, because it’s of particular importance for haemostasis, is something known as positive feedback pathways. Now positive feedback pathways are systems that perpetuate themselves. So, if you like, the outcome of a particular response makes that response happen even more, if you like, like a chain reaction. Now there aren’t that many examples of positive feedbacks within our human physiology.

But for some reason, and maybe it’s because haemostasis is so important, several of the examples that are known happen within the haemostasis system. The reason it’s so important is this chain reaction enables a response to happen exceptionally quickly. So the first process or the first haemostasis system that I introduced was platelets. Now platelets have the ability to recognise tissue injury. So when they’re circulating in your blood, they’re normally in what we would refer to as a resting state. But they have proteins on their cell surface that enable them to recognise injury. In fact, they recognise molecules that they wouldn’t normally see within the circulation.

But when the circulation becomes broken and the cells and the blood are able to leak from the circulation, they encounter a whole range of different molecules. And principal amongst those are proteins of the extracellular matrix. These are the proteins that hold your tissues together, the proteins between the cells in your tissues. And they also hold together the cells within the wall of the blood vessel. So as leakage starts to occur from a broken blood vessel, one of the first things that platelets encounter is collagen. The platelets stick to the collagen. And this then stimulates a whole rapid process that leads to their changing their behaviour quite dramatically. The platelets become sticky. They change their shape.

And importantly, they secrete and release a whole range of other factors that also activate other platelets. So this is an example of positive feedback pathways, because this tells other platelets in the surrounding environment also to become activated. They, too, become sticky. And they become sticky particularly to bind to a protein that’s found in the plasma known as fibrinogen. The fibrinogen binds to the platelets and literally glues them together. So the platelets initially stick to the damaged sites. They become activated. And then they stick to each other, forming what we would refer to as a thrombus. And this literally plugs the hole and prevents the further loss of blood.

Now the important thing to remember about platelets is they principally perform their function within the arterial circulation. So they perform their role where blood is flowing quite quickly. This is fairly counter-intuitive because they have to do this quite complicated process. Whilst the blood’s flowing quickly, they have to grab hold of the site of injury, become activated, and stick together. But there are various little tricks they’ve adapted to enable them to do this very, very effectively. So it’s important to remember when we hear about processes that go wrong with our cardiovascular physiology in cardiovascular disease - if that happens in the arterial circulation, there’s a good chance that platelets have a role to play in that process.