I agree, I have 2 mutations but my platelets are reasonable at around 500. My Dr wants me to start hydroxy but because I'm very healthy with no other risk factors I'm gonna just take aspirin for now. This will probably change eventually but I will take a wait and see approach for now.

Dear Mark and Patty,

I will try to explain the information I posted with analogies, to make it easier to understand.
The genes that cause our essential thrombocythemia and other MPNs not only make our bone marrow create too many of a certain type of cell, platelets in the case of ET, red blood cells in the case of PV, etc., but these genes can influence the shape of these cells (normal, too big, too small, misshapen, etc.) and even the way these cells function and behave.
This is similar to, for example, genes that influence our other characteristics. Genes are behind us being tall or short, having a fast or slow metabolism, being impulsive of being controlled.

Regarding our platelets being hyperactive: imagine that our platelets in ET are like that friend of ours who is fast to anger, who basically needs very little before they burst into anger. And imagine that friend in a bus that is overcrowded or when they are almost missing a flight. They will get very angry and they will pick a quarrel with many people.

Platelets are like that impulsive friend, easy to get hyperactive (angry) and then they clump together (get glued together) to form very small blood clots when hyperactive (angry). And some arteries in our body are places with a bit more stress, like a buss full of people is for that impulsive friend.

After the platelets formed these small blood clots due to hyperactivity, our body will do its usual function of breaking down these small blood clots. But like when we use superglue to glue two plates together, when we force them apart, they will most likely break and we end up with two unusable plates. The same applies to these platelets when the body breaks down the small clots: the resulting platelets are like the plates, dysfunctional. In the case of platelets, the dysfunction means a different thing, they have used some substances they secreted in the process of getting glued to other platelets and now they do not have those substances anymore, so they cannot do their job properly anymore.
And that can give us a host of other problems.
This is oversimplified, of course, but the gist of that article.

In short, our genetic mutations behind our ET not only tell the bone marrow to make too many platelets, but they also influence how these platelets are shaped, how hyperactive (angry) they are, and also influences their tendency to clump together (glue) to form blood clots.

I hope this helps with making the content of those articles easier to understand.

Best regards,
Tatiana

Doctors like to focus on platelets, but keeping WBC < 10 and HCT < 45 (42 for females) might actually be more important for overall outcomes. The highest my platelets got was probably about 2 million. It was 1.68 million AFTER plateletpheresis. 1 million plus was my normal for a while. Things were looking dire before I got on Jakafi + Pegasys. Now I have to keep reducing my doses because my counts are a little too good.

Wow Tatiana, that's an Einstein like answer. Is there any chance you could give it to me in easy to understand terms, Lol!

That is correct. There is no linear correlation between platelet numbers and risk of thrombosis. At higher levels, there is an increased risk of hemorrhage however.
One of the theories has to do with a change in the behavior of blood cells. Due to the JAK2 mutation, blood cells can become "extra sticky", increasing risk of thrombosis. This is why many MPN Specialists no longer use "normal" platelet levels as a target. There is no evidence that this correlates in a linear fashion with a reduced risk of thrombosis., It is more complex than that.