G20210A

My mutant power: hyper-coagulation

In 2005, I had a deep vein thrombosis episode. I learned a lot about the way blood works and why this condition exists. There is enough of a cautionary tale here to make it worth sharing the story.

What is the natural state of blood?

Your blood does not clot because it is exposed to air. It clots because it becomes unexposed to your natural anticoagulants, which are keeping it liquid in the first place.

As it turns out, the natural state of blood is, surprisingly, a solid (clotted). And when you end up hearing why this is so, it turns out to be not that surprising after all.

The number of places where you want blood to be liquid/mobile is easy to define: inside your veins and arteries. If you are leaking on the inside or the outside, you really want to prevent drainage if you can. But the number of different ways you might leak – by puncture – is so great, that it would be quite complicated. As a result, the inner walls of the vessels where you want blood to be flowing, as well as your red blood cells, all release anticoagulants that inhibit the clotting process. When you leak for any reason, you are un-exposing your blood from its natural anticoagulants and the clotting process, which is always trying to take place, is now uninhibited and so it takes place.

As a result, if you have any situation in which your natural anticoagulants are used up, internally, your blood will begin to clot. And this simple idea is the origin of many of the clotting disorders that we have heard about with increasing frequency since the mid-1990s.

And, yes, it does mean that the little vials they use to collect blood samples, and the bags used by the Red Cross, all have anticoagulant in them.

Slowing down circulation

This one is straightforward. If you slow down your circulation, you could end up reducing the level of your local anticoagulants due to lack of good mixing. Traveling in the pressurized cabin of an airplane, where the blood begins to pool in your lower legs anyhow, is the first of a few bad things. The blood from your lower legs needs the flexing of your calf muscles to help return blood efficiently, and sitting in a cramped-up position with the edge of a hard seat against the back of you legs is not contributing to good circulation. Neither is the dry, dehydrating environment, including consuming dehydrating agents such as alcohol and caffeine.

Stay hydrated, move around. It actually matters.

Whirlpools in the heart (about 4% of the global population)

One of the common consequences of atrial fibrillation is a flutter in the normal working of the heart that ends up creating a small whirlpool of blood inside the heart. See the problem? If the blood is not circulating (mixing with its surroundings) then the natural anticoagulants are used up and clots form.

Genetic Mutations (about 5% of the population of European origin)

There are five know genetic mutations that lead to hyper-coagulative disorder. The most famous, and most common, of these is the factor V mutation (also known as Leiden V). It is a single-point mutation (G1691A) that prevents efficient inactivation of factor V during the clotting process. When factor V remains active, it facilitates overproduction of thrombin leading to generation of excess fibrin and excess clotting. Not everyone who carries these mutations automatically develops clotting problems, such as DVT (Deep Vein Thrombosis), but when you couple the mutation with bad behaviors, you increase the risk.

The second most common mutation is G20210A, with another single-point mutation that results in the overproduction of prothrombin, thus enhancing the clotting process. In this case, the mutation is not expressed, as the G20210A is on a non-expressed part of the tRNA, and so the sense of it is that the degradation of the tRNA is slowed, resulting in the overproduction of prothrombin and so a hyper-coagulative tendency.

As it turns out, I have the G20210A mutation.

(A) It shows up on routine genetic testing, such as 23-and-me, and I am definitely in favor of routine genetic screening.

(B) I was a prime candidate for trouble: G20210A with lots of air travel, sitting in airplanes with crossed legs and staying still and relatively dehydrated.

The prescription, once you understand the condition, does not require being on hard-core anti-coagulant therapy. So far; so good. Results may differ.

(1) one full aspirin a day probably helps bring me down to normal
(2) OTC compression hose to help the lower leg pooling
(3) more significant hose (ca. 25 mm Hg equivalent) when taking to the air
(4) injectable 12-hour anti-coagulant on trips over 4 hours (partially hydrolyzed heparin)
(5) for trips under 4 hours, then a 3-day window of time fore and aft with no other air travel, and 3 days on the ground
(6) for trips over 4 hours, 5-day windows

So far, so good.

What survival advantage is conferred by hyper-coagulation?

This is (of course) speculative, but here are two facts:

(a) the occurrence of the G20210A mutation is strongly correlated with people of European origin and the divergence dates back to the end of the last ice age

(b) women (today) who carry the mutation are less inclined to bleed as profusely during childbirth

It makes a compelling story. Under the stress of the migration that is proposed to have taken place during the last ice age, women who did not bleed as profusely during childbirth may have preferred this condition as a survival advantage.