Hi @1pearl, I’m putting together pieces of your ET puzzle. When we first spoke the other day, you mentioned not having the JAK2 mutation and the mystery as to why you have elevated platelets. Reading through your response to another member this morning, I see that you have the CALR mutation. That’s the missing piece of the jigsaw puzzle that fell through the cracks in our discussion.

The CALR mutation is also one of the potential causes for development of a myeloproliferative neoplasm (MPN) such as ET, PV, MF.

MPNs are a type of chronic cancer of the bone marrow that can worsen over time, especially if left untreated. They happen when immature blood stem cells, called blast cells, develop sudden genetic changes that cause them to grow abnormally and out of control. In the case of ET it is platelets. MPNs can also lead to complications like scarring of the bone marrow in MF or myelofibrosis which eventually interfere with production of healthy blood cells causing severe anemia and low numbers of platelets.

Some of the more common genes involved in the mutations known to cause MPNs is Janus kinase 2 (JAK2). However, other gene mutations, called MPL and CALR are also culprits.

A quote from an article in the National Institute of Health/PubMed
“Calreticulin (CALR) mutations have recently been reported in 70–84% of JAK2V617F-negative myeloproliferative neoplasms (MPN), and this detection has become necessary to improve the diagnosis of MPN.”

Link to article: Calreticulin Mutations in Myeloproliferative Neoplasms: Comparison of Three Diagnostic Methods https://pmc.ncbi.nlm.nih.gov/articles/PMC4621046/

Every second, our marrow produces several million blood cells. Daily, that translates into around 200 billion red blood cells, 400 billion platelets, and 10 billion white blood cells. Each cell is a precise copy of each other! If there is even one teeny deviation to a strand of DNA it can alter the course of events. Our immune systems do an amazing job of sniffing out defective cells and eliminating them. However, if the cells elude detection they can proliferate out of control, eventually crowding out the healthy cells. So keeping them under control can be vital to continued good health.

A little reading material… (There are many reputable sources online regarding MPNs or specifically Essential or Primary Thrombocythemia)
https://www.healthline.com/health/cancer/myeloproliferative-disorders
So, for what it’s worth, there’s the missing piece. The CALR mutation. Hopefully this is helpful in clearing up part of your mystery.
Have you considered a 2nd opinion?

I understand you don't want to take meds until you are satisfied you have been properly diagnosed.

I will say that, besides lowering clot risk, benefits of HU also include lowering the chances of spleen enlargement (Dad had this uncomfortable and disfiguring condition until he started meds) and keeping LDH within normal parameters, basically keeping your liver from getting overworked is how it was explained to me. My LDH was high until I started HU. I also felt less fatigue on HU.

No, HU won't cure ET or stop progression to MF or AML. But it may slow things down, especially if your diagnosis comes after age 50.

I feel that I was carefully and properly diagnosed 10 yrs ago. But I don't feel that I get much quality doc time or info. Oncology offices are full of acute cancer patients, and the medical system is set up to short-sheet chronic cancer patients like us because we are not on the verge of a crisis or death. For example, I waited 45 minutes in the exam room at my last visit because the oncology nurse was dealing with a kid with leukemia and her parents.

When I wandered out to the nurses station to make sure they hadn't forgotten me, there were five PAs returning phone calls or calling people with lab results and trying to sked appointments.

They were also short-handed because it was December and the hematologists were all at the ASH conference. (Note to self: Don't let them sked you for Dec appts.)

Also, COVID drove a lot of people out of health care in my area, and it exposed a lot of worker safety issues that have led to labor disputes.

Add to that the general stinginess of most health care insurance or advantage plans.

All that affects the care we get.

You can go to alternative medicine clinics where they have relaxing music, aromatherapy, and lots of sympathy. But the treatments are expensive and don't work.

So: I get that you are frustrated and angry and you want confirmation of your diagnosis with a bone marrow biopsy.

None of us, of course, is capable of getting into the weeds interpreting your test results or explaining a sudden drop in platelets without meds.

Only thing I can suggest is to you ask your GP to refer you for a second opinion. I sure wish I could help more.