Thrombosis causes

Thrombosis is the formation of blood clots in the wrong location. Effectively, they occur within the circulation, so within a blood vessel. And this leads to basically them becoming clogged up and preventing the flow of blood to downstream tissues. Now I’ve described the fact that within the haemostasis system that the responses are extremely rapid. They’re almost explosive in nature. Because of this, it’s really important that the body is able to control these processes and prevent them from happening at times and sites when they shouldn’t normally occur, such as within blood vessels. It’s also equally important that they activate and blood clots form when injury occurs.

The way that the body actually prevents the unwanted activation of these systems is that the healthy circulation sends signals into the blood, particularly cells that are found within the lining of blood vessels known as endothelial cells. And these release factors into the blood that are able to tell platelets not to become activated. They’re effectively signals that tell them that everything’s fine. There’s no reason to become activated, no reason to become sticky. And this dampens down their responsiveness. Now these factors are released into the blood all of the time, and this prevents unwanted activation of the processes. And that principally affects platelets.

There are other processes and other proteins and other factors that are present within the blood that normally dampen down the coagulation process as well. But the problem is within several aspects of cardiovascular diseases, these inhibitory processes become defective, and this leads to unwanted coagulation or activation of platelets. Another reason this can occur is that the development of disease actually stimulates these processes to occur. And a very good example of this is atherosclerosis, which was discussed in an earlier session. Now atherosclerosis, as you will be aware, is the formation of lesions within important blood vessels, arterial blood vessels. And these fatty lesions start to occlude the blood vessel. Now some lesions are unstable, and they rupture.

And when they rupture, they leach all sorts of nasty factors, oxidised lipids and necrotic debris from cells that were deep within these lesions within the blood vessel wall. And these factors activate platelets. So the plates become activated. They also can influence activation of the coagulation pathway as well. But principally, it’s the platelets that become activated. They stick to the area of damage and a thrombus rapidly starts to form. And because of the positive feedback systems that I’ve described, this leads to very large thrombus very quickly, which can completely occlude the flow of blood.

Platelets are also involved in the development of these lesions over many decades as well, so they also have a role in the ongoing process of the formation of these lesions. So atherosclerosis is clearly an important trigger for thrombosis. But there are other reasons why it can occur, too. For example, it’s often found that individuals with other risk factors, such as high cholesterol, may have very sticky platelets. They’re more prone to become activated. It’s also found that individuals with cardiovascular disease are less sensitive to the inhibitory signals that are sent out by their healthy blood vessels. And this, again, can lead to unwanted activation of the clotting processes.

So cardiovascular disease is linked very broadly with the unwanted triggering of the coagulation processes in the circulation. So thrombosis can also occur in the venous circulation, principally, as I’ve mentioned, through activation of the coagulation pathways. The reason why this occurs is largely due to loss of blood flow. So, for example, a very common occurrence of venous thrombosis is referred to as deep vein thrombosis, which occurs within the large veins within the legs. And this usually occurs due to stasis or lack of movement, maybe associated with a long period of bed rest. For instance, patients in hospital may be prone to this.

And in fact, that’s the reason why surgical stockings are often used to prevent the pooling of blood in these veins within the legs. There are other circumstances this may occur, long-haul flights, for example. Long-haul airplane flights can also result in increasing the chances of this occurring. So essentially what happens in these cases is that the coagulation process is triggered due to the loss of flow of blood, and large clots can form within these vessels. These large clots can become particularly dangerous if they embolise. Now embolisation is the process whereby fragments of clots will come away and then be carried off in the circulation.

Because the size of these clots can be quite large, they can be quite damaging to the circulation they encounter further downstream in the circulation. And for deep vein thrombosis, a major worry is a condition known as a pulmonary embolism. So emboli, or the smaller clots, may become disrupted and fall away from the main clot. They travel back to the heart and then pump back through the circulation into the pulmonary circulation, where they become lodged in small blood vessels in the lungs. Now, this can be exceptionally painful and is life-threatening.

So it’s important that we understand the processes that control the coagulation process, that control platelet function and haemostasis as a whole so we can try to understand what goes wrong in disease and how we might better be able to control this.