One year later - need help everyone

[cmc_ufl]

It has been 1 year since I joined this wonderful forum. This is a great place. Thank you all.

I need help deciding what to do moving forward.

I am a 30 year-old father of two small children. One year ago (Jan 2021), at my first GP appt in 10 years, my CBC showed platelets at 437. My GP asked if I had ever had high platelets before, so I checked my past CBCs. In 2008 (age 17) my platelets showed 380. In 2011 (age 20), my platelets shows 455, 462. None of my past doctors questioned it.

My GP referred me to hematology, where he (not an MPN specialist) told me “I think you have ET”. He tested my counts, came up 495 (A little high, I was under severe stress from the situation). I then found an MPN specialist to take over my care, and he tested me for JAK2, CALR, and MPL, all negative. Blood smears showed elevated platelets with normal size and shape, no clumps. He also tested my blood a few more times. At this point, all my CBCs are the following:

2008 (age 17) - 380

2011 (age 20) - 455, 462

2021 (age 30), 437, 495, 442, 429, 408

2022 - 470

The MPN specialist says that because my genetic tests for the 3 mutations all came back negative, along with the fact that my counts are only over the 450 line half the time, that a BMB is not strictly necessary and that no further workup is needed at this time.

I am concerned I am undiagnosed ET.

Main reasons for my concern:

1) half my counts are over 450, dating back 10 years

2) The limit of detection (LOD) on the CALR and MPL tests he did were not that great. CALR LOD 6% allele burden, MPL LOD 20% allele burden, meaning that any allele burden below those values would be a false-negative. I’ve seen several people on this forum with allele burdens for CALR below 6% and MPL below 20%. The only test I am confident in is the JAK2, which was negative with a LOD of 0.1% allele burden.

The way I see it, I could still be triple-negative ET, or have CALR or MPL with low allele burden.

Considering all this, especially my counts and tests, should I let this go, or pursue it further? I’ve been down this road for a year now. I need to either drop this, or ask for further testing.

What would you do?

[EPguy]

You may have read discussions here about PLT. Mildly elevated, and stable, are not necessarily a concern. And yours appear fairly stable. By comparison I had 387 (2013) 645 (2016) and then over 1000 (2020). No question there.

For the CALR test (and maybe MPL also) I believe they sometimes use a different procedure to get the sensitivity once Jak2 is found to be negative. You may want to ask about that. Otherwise the triple negative MPN is possible.

You don't mention the other CBC results, HGB, HCT, WBC, etc. Are all of these normal? If yes that may be why your Dr is ok with it.

Also blood LDH is relevant to MPNs.

There are other causes for elevated PLT than MPN. Have you been through all these possibilities already?

[cmc_ufl in reply to EPguy]

Secondary thrombocytosis ruled out, under the assumption that if it were an infection or malignancy, I would be dead by now (elevated at least 11 years now)

WBC normal (usually 6-8K)

RBCs normal, although high normal. HB 15-16, HCT 46-47

LDH normal, top 30% of reference range

Blood smear showed normal platelets, normal shape and size, no clumps, no bizarre forms

[EPguy in reply to cmc_ufl]

My take is your Dr is giving you good advice. Makes sense that you continue to get CBCs more often than normal to track the numbers. In medical stuff, big or sudden changes are often more interesting than a specific state. (extremes excepted of course)

You could also ask your Dr to be sure the best available allele test was used for any non-jak2 mutations.

You could also ask about low dose aspirin. It's a common Rx for younger MPNs if your Dr feels you have any relevant risk factors.

[cmc_ufl in reply to EPguy]

Thank you. Yes, I plan to follow up on more sensitive tests. Will update when I have more info.

[cmc_ufl in reply to EPguy]

Could you elaborate a bit, or provide a reference, on your statement that “mildly elevated and stable” are not necessarily a concern?

[EPguy in reply to cmc_ufl]

Thanks for the motivation to look further into it. It has been a topic on the Voice and my Dr has discussed with me. When I was up to 600+ my general Dr didn't freak out, but probably should have acted by that time. At 1000 he did act.

In the link here, at a lower limit of 600, ET is "a consideration" while "rarely " so below that. They define 350-600 as "high normal". As usual this info needs to be considered by us and our Dr with the other data that we have in getting our Dx. If for example an abnormal MPN type BMB is found, mildly elevated platelets would be more suspicious.

lls.org/sites/default/files...

<<Normal platelet values

range from about 175,000 to 350,000 platelets per

microliter (μL) of blood in most laboratories. ET is a

consideration if the platelet count is above 600,000/μL of

blood and remains high over a period of observation. Most

ET patients have more than 600,000 platelets per microliter

of blood. Rarely, ET is diagnosed in patients with platelet

counts that are high normal (between 350,000 and 600,000

platelets per microliter of blood).>>

[cmc_ufl in reply to EPguy]

I wonder how it being rare to diagnose ET less than 600 fits into the 2016 WHO diagnostic criteria of 450+. Seems like that document is kind of dated (2012). It’s interesting because I see many people here on this forum with counts less than 600, some even 400-450, who just happened to get a positive driver test. That’s the frustrating part in my situation: borderline platelets, no positive test. I could be healthy, or I could have a full-blown MPN going completely undetected.

[EPguy in reply to cmc_ufl]

Good catch on the 2012 date. I prefer reports not before 2017.

In this booklet form the same group last year the numbers are more precise.

lls.org/sites/default/files...

<<In patients with ET, the platelet count is higher than 450 x 109/L (a normal platelet count ranges from 150 x 109/L to 450 x 109/L)>>

450 is higher than the normal limit (369) shown in most my CBC results. See image of my plt history, the limit (upper green line) seems to change regularly from 370-400. So in this case, "mildly elevated" would be that area from 370-450, right where you are. I see other institutions that have currently this limit from 400 - 450.

PLT range

[EPguy in reply to cmc_ufl]

You might find this Voice post and replies interesting, similar to yours:

healthunlocked.com/mpnvoice...

Might be good to ask "Hamburger21" how it's going.

[mhos61 in reply to cmc_ufl]

That would be me (platelets less than 600)...!

Diagnosed 2016 ET (Jak2+) platelet count 500! This was in a random blood test.

Had my GP not been cautious and flagged/monitored/ and referred me to haematology all within a six month period, I could potentially have been in danger of suffering a thrombotic event.

I am very grateful to my GP for following the 450 platelet guidance.

[hunter5582]

I would note that at your age and with your symptom pattern even if you do indeed have ET your most aggressive treatment would be aspirin and monitor. Some docs would not even recommend the aspirin. You are correct to note that a triple negative ET is a possibility. Also the possibility of a false negative. Also the possibility that you are just someone who has a bit higher than normal platelet levels in the absence of any disease.

My own take on this is influenced by the fact that I have managed a MPN for 30 years since I was in my 30s. I have lead a rich life and continue to do so. I raised two kids and now am blessed to be a grandfather. I would suggest that you plan to do the same regardless of whether you do or do not have ET.

There are things you can do to ensure you live a rich life. Maintain a healthy lifestyle with diet, exercise, cardiovascular condition, etc. Avoid the toxins and carcinogens that you can, including those in the food stream. These things will protect you whether or not you do have ET.

The other thing has to do with the impact of attitude and your approach to life. This has a profound impact on your physical and mental health. These things are not actually sperate. The mind-body connection is quite powerful. To quote Frank Herbert "Fear is the mind killer." The body killer too. Controlling what we can and letting go of the rest is essential to managing a MPN or any other condition.

You have two wonderful children to raise and a rich life to lead. You cannot control whether or not you have ET. You can control how you manage your life and any condition you encounter. My suggestion would be to focus on living a healthy lifestyle to give yourself the best chance possible to enjoy your grandchildren. Continue to monitor your status and get a CBC on a regular basis. Definitely investigate if you see an upward trend in platelets over time. If things stay stable and you hover just a bit over normal, give it a couple of years and retest.

All the best my friend. And do plan to be a grandfather. it is really great!

[cmc_ufl in reply to hunter5582]

As always, thanks for your input, Hunter. May we all learn to take life one step at a time, working at what we can change, and accepting what we can’t control. Fear is truly the mind killer. If I’ve learned anything over the last year, it’s that life is short and worrying about the unknown does absolutely no good. Wish you the best. Will update when I have more info.

[EPguy]

There is another way to look at it; if the uncertainty is causing you incurable stress, that alone is a substantial risk factor. In that case a BMB could be justified to put away the uncertainty and improve your prognosis with or without MPN.

[cmc_ufl in reply to EPguy]

Have thought about this many times. Thanks.

[katiewalsh]

My first question is whether your MPN doctor is good. I had one once who gave me 8 years to live. That was 7 years ago & I still feel good except experience some fatigue. If I were in your shoes, I would not get a BMB. First, your doctor didn’t recommend it but more important is that it very well might show no fibrosis. Given your CBC, I’d be surprised if you had any. And if there’s no fibrosis you don’t know anymore than you do now. I fully understand your wanting to know & to have some certainty. It’s hard. But I suggest you follow the excellent advise given by Hunter. Best of luck. Katie

[cmc_ufl in reply to katiewalsh]

That is exactly what the MPN specialist said. A BMB in my case could very well be non-diagnostic. Therefore, he does not feel strongly it should be done. I’m just one of those rare people where the platelet count is in the gray area - could be normal, could be a mild MPN.

[Mostew]

Building strong foundations makes a good house . I would work on lowering stress levels , keep an eye open for concerning symptoms and if you feel it's a good idea pursue the tests . BUT leave tests for now if it causes worse anxiety

Not easy ....

[cmc_ufl in reply to Mostew]

Thanks. Yes, you are correct. Not easy at all, especially dealing with this as a young patient where the consequence of a missed diagnosed could have significant impact on my future outlook.

[mhos61]

Only you can decide whether to let this go, or pursue it further. I suspect this will depend on how the ‘not knowing’ is impacting your quality of life. The thing is you may pursue it, and still have no conclusive answers.

It’s certainly a dilemma for you, the reasons you outline are somewhat concerning. Yet, it’s very encouraging that your counts have been stable over a long period of time. Likewise, your blood smear showed no anomalies. If you can learn to live with that knowledge, continue to have regular cbc checks, maybe you can begin to move forward.

If the anxiety proves too much, then research better testing services for the limit of detection for the CalR and MPL mutation. You could also contemplate a second opinion with another MPN Specialist. There will be differing opinions/approaches even amongst MPN Specialists. It may be the key to putting your mind at rest.

[cmc_ufl in reply to mhos61]

Thank you. I have thought about seeking a second opinion and looking into better tests. I will update when I have more information.

[Wyebird]

Hi it’s very rare for me to read all the replies one gets when posting a query. In your cause I’ve read them all. I think they all have value. If the unknown is stressing you ( I know I would be beside myself)how about you consolidating everything that has been said, Talk to your GP explain you feel stressed. Ask if your platelets could be monitored every 4 months. Ask if it would do any harm to take baby aspirin as a precautionary measure.

Before going down this route look at your health insurance. At the moment you are not diagnosed. Once you are this will be affected.

Good luck

[cmc_ufl in reply to Wyebird]

Thanks. We are currently doing 3-6 month CBCs. Insurance is also an important consideration. Once you’re diagnosed, you’re often stuck with your current level of coverage. Great advice.

[MaggieSylvie]

Hi cmc, You've got lots of helpful replies here whose advice is good. I just want to add that I have MDS as well as MPN with thrombocytosis. I have no idea whether this is essential or secondary or what! I was diagnosed about two and a half years ago with a painful BMB and put on aspirin and watch and wait because, like you, my platelets were high. They hover between 500 and 600 and my haematologist is happy with their stability. When I asked her when she would worry, she said"When they reach 1000". I am in my late seventies and at the time of being diagnosed I was given a prognosis of ten years ??(i.e. eyebrows raised). I think she thought getting to the eighties would be enough for me! So I worried about that because that wasn't my idea of life. I've had some skeletal issues since then that have really stopped me in my tracks, but apart from that, I think I'm quite well, and these prognoses are not really reliable. They are based on averages from small numbers in the past, and I don't think they can be taken seriously. As they say - Just look after your health and enjoy your life.

[cmc_ufl in reply to MaggieSylvie]

Thanks for the reply

[Joetcalr]

Good advice already, just to add in to eat a Mediterranean type diet. My platelets were 1650 before my MPN was discovered, maybe because of my diet.,so you've a way to go yet. I'd be wary of aspirin if you're Calr mutation. Best regards Jo

[cmc_ufl in reply to Joetcalr]

Many thanks for your reply. Best wishes for you.