Coagulation

So the second major system that enables the blood to clot in this case is the coagulation system. Now, importantly, the distinction from platelets is that coagulation principally occurs in the venous circulation. So this is in blood vessels that are flowing as quickly under less pressure. And these are systems that are regulated differently. Now coagulation, as I mentioned, is the conversion of liquid blood into a gel-like substance that plugs the hole at sites of injury. So coagulation is controlled by a number of different factors that are present within the blood. These factors recognise, if you like, an alien environment to them. They recognise that something has happened at a site of injury.

There’s a number of different ways these are triggered, which include binding to extracellular matrix proteins, again, like collagen or charged surfaces that are exposed at sites of injury. But the other way they tend to work is to recognise protein, or a particular protein, and its tissue factor that is expressed or present on the surface of cells at sites of injury. Now this triggers off a very complex cascade of biological reactions. This cascade involves multiple enzymes, and that also speeds the process up and amplifies the reaction. But the ultimate aim of this pathway or both of these pathways of chemical reactions is the formation of an enzyme, an enzyme known as thrombin.

Now thrombin is what we would refer to as a protease. It’s able to chop up proteins, but particular proteins in a particular way. And one of its targets is the molecular I’ve referred to just now, fibrinogen. Remember, it’s the molecule that binds platelets together. Well, it has another role. It’s cleaved. It’s chopped up, or a small portion of it is chopped out by the enzyme thrombin. This, then, enables the protein to assemble into long strands and polymerise. And it’s the polymerisation of this protein into long, insoluble structures that turns the blood from a liquid into a gel-like substance. So this also occurs simultaneously with platelets becoming activated on occasions.

And this is another point at which positive feedback occurs because thrombin, which, as I’ve mentioned, is essential for the conversion of blood from a liquid to a gel-like substance, also activates platelets. So this whole system amplifies itself. The coagulation pathway talks to platelets, and they then become further activated. Another important positive feedback system is the fact that thrombin also activates or enhances some of the earlier steps in the chemical reactions that lead to its own formation. So again, this enables an explosive reaction. While clearly the activation of platelets and the formation of blood clots at sites of injury are absolutely essential, these systems do have a darker side.

They’re highly involved in triggering thrombosis, a condition that forms the basis of our next session.