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Thrombosis and genetics (part 1)
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Section 1: Thrombosis and genetics
Chapter 36. Thrombosis and genetics. A specific training for counseling for the Thrombo Sensor. You will find the Thrombo Sensor here. It has two different functions. One is prevention against developing thrombosis. It is not particularly helpful in early diagnosis when thrombosis occurs. It is not really much of a benefit here, but treatment can be improved with the Thrombo Sensor. Let me explain the concept of thrombosis.
If we look at the cross section of the skin here. We have the skin surface, the blood vessels and blood platelets, which are a kind of motor for building blood clots. If we look at the different genes and proteins that are active in blood, there is the factor5 gene. This gene produces factor-V protein. A gene is always instructed on how to build a protein. So, we have the protein here and this is built in a way that is still inactive. So, we have the factor-V protein that is inactive and it is floating around in blood. Then, there is another gene called prothrombin. This latter builds protein as well which also inactive. So, these two genes produce their proteins and they are inactive and float around in blood. Each of these genes produces a lot of these proteins which are all inactive.
Now, we have a person who stepped on a nail. This nail erupted some blood vessels and some tissues. Then, let us have a look at what happens. Blood and nail, the following occurs. This stress on the cells or on the tissues is recognized. Then, factor-V protein is first activated. This long chain is cut open and it is combined to look like this, this small molecule in there combining the two and holding them together. The factor-V has now been activated. Then, it has an activating function of the prothrombin. This latter is then activated. When it is active, it causes more factor5 to be activated. You get this kind of circle; once this is activated it activates the prothrombin and then more and more is activated. It is like a kind of a positive feedback mechanism. This leads to lots of factor-V being activated, lots of prothrombin being activated. In a simplified manner, the prothrombin then indirectly causes the platelets to bind together and produce blood clots to close up the wound. This is what you want to do, otherwise you would bleed to death. This usually happens quite quickly in people with normal genes in this case.
This is the normal process that you would want to happen. The wound is closed up. The body recognizes ok it is enough. We do not need this function anymore. Then, there is this protein, the APC protein. This protein is kind of an enzyme that degrades the active factor-V. It eats it up. In the end, you do not have any factor-V left. This makes sure that the normal prothrombin is activated. It is also lost and then in the end you gets back to the normal state; the wound heals. This is what normally happens when you hurt yourself. The wound heals and then everything is back to normal.
Now, let us look at the genetic variations. If a person has a genetic variation in the factor-V gene, and the same process happens, what happens is that factor-V protein is built in a slightly different way. It is not constructed as expected, but it has this modification here. Now, the factor-V protein, with all of these errors, is floating around and the prothrombin in this case is normal. Again, you have the tissue damaged and then factor-V is activated, just like before. That then activates the prothrombin. The cycle begins and more factor-V is activated and more prothrombin is activated, which then closes up the wound.
So far, it is still all the same, but once this has been done, the tissue says ok it is enough, we now want to break down factor-V again. Then, the APC comes along, but this factor-V molecule is quite persistent to break down. It resists being broken down and it has this tendency to cause more blood clots to be formed. This is the real problem because in some cases even when there is no damage to the tissue, these blood clots can form because factor-V is just so potent in creating blood clots and it is so resisting to being broken down to avoid this that it can cause blood clots. They then block up some blood vessels and they restrict blood supply to parts of the brain or somewhere else. Then, this becomes a severe and a deadly situation. If it happens in your leg, for example, it is called thrombosis. If it happens in the brain, it is a stroke. It can be a heart attack if it blocks up in the heart or a pulmonary embolism if it blocks up the blood supply to the lungs. Many of these are very dangerous occurrences.
So, what we can tell when we test the relevant genes, we know that if the factor-V gene has a thrombosis, the risk is 8 to 80 fold increased compared to a person with no genetic variations. Then, if the prothrombin gene has a genetic variation, it is 5 to 25 times increased risk. Then, there is another gene, called venous thrombosis, thrombosis in the veins and blood vessels that go back to the heart. The arterial thrombosis is the blood vessels that go away from the heart. There is a genetic variation that increases the risk 1.84 times. This is the genetic risk. So, there are a number of risk factors that especially people with increased risks should avoid not to increase more the risk and that even reduce the risk compared to other people with the same genetics.
There is something called the »economy class syndrome« because people sitting in a plane for ten hours have an increased occurrence of throbosis. Sitting for ten hours causes blood clots to form in the legs and this can then cause thrombosis in the day after. So, sitting in a plane for 10 hours is a risk factor, that is why some people should take blood thinners if they have a high genetic risk when they are on planes. Smoking increases your risk 1.52 fold. Especially for genetically predisposed people, it should be avoided.
Then, after surgery, when you are lying in bed in hospital maybe for some weeks is also a very strong increased risk. Blood thinning should also be taken during that time. For women only, there are the hormonal preparations like the contraceptive pill or hormone replacement therapy by themselves increase thrombosis risk 2 times, but in combination with a genetic variation, it is 15 times. So, risks multiply each other and become much more significant. Then, hormonal preparations and hormonal drugs should really be avoided if possible or combined with a blood thinning therapy. In addition, pregnant women generally have a 4 times higher risk of developing a thrombosis compared to non-pregnant women. If combined with a genetic variation, it is 60 fold risk. It is a very high risk and these women should be treated with heparin to protect mother and child from this dangerous concept. There is more information about the hormono therapies and pregnancy in another training. This is supposed to show you the concept of how thrombosis is generated and what we can tell from a genetic test.
That is the end of chapter 36, thrombosis and genetics (end).
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Thrombosis, hormones and pregnancy (part 2)
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