I found this forum after googling why my platelets have been consistently higher than reference range for years.
I am 28, and my platelets have consistently been 440, most recently in Feb were 467.
The doctors didn't seem concerned though when I queried it last year and just say that must be normal for me. But something in me wants to know why they are still rising, even if it is slowly.
I don't know much about ET, and perhaps the doctor is right and it might just be normal for me and nothing to worry about. I know that it is not a super high amount, just over the high ref limit, but I am just wanting advice and others to talk to really from people that have experience of this?
Thankyou 😊
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Take a look at my profile and posts. Same exact situation. Went through full work up three years ago at age 30 after a new doctor finally referred me after 10+ years of 400-450. Negative for all driver mutations. Hematology ultimately told me “you might have it (1-5% chance), but you probably don’t, so you need to either have a BMB (which would possibly be inconclusive) or learn to live with the uncertainty.”
Three years later, I never had the BMB (their recommendation was no further action despite not 100% ruling it out. My platelets remain stable 400-420 at my annual checkups. Turns out my mother and two young sons also have elevated platelets in the same range. Possibly just a benign cytogenetic abnormality in my family, but I will never know for sure.
If your mother and children have higher platelets too, then you should know that there is ET that can be hereditary and also ET that is familial.
My dad and his mom had high platelets, I have them too and I am the only one who got the diagnosis. And it is a hereditary ET in my case. This means that I inherited the pathogenic genetic mutation from my dad who inherited it from his mom. There are also cases of familial ET, and in that case one does not inherit the pathogenic mutation itself as much as the predisposition to acquire it.
My mutation is a non-canonical MPL mutation, MPL R102C, similar to MPL R102P, and it is found in hereditary ET.
There are ways to know for sure: NGS (genetic testing) on all potential pathogenic mutations and TPO levels in everyone affected.
I think it is important to distinguish here hereditary/familial ET from hereditary/familial thrombocytosis. Do any of your affected family members have evidence of progression (development of leukemia or other blood disorders/cancers)? Any evidence of bone marrow scarring? There are benign and malignant forms of thrombocythemia/thrombocytosis. ET is malignant, others are not.
Thrombocytosis, if without any other cause, meaning primary thrombocytosis, is essential thrombocythemia (ET). Reactive thrombocytosis is secondary thrombocytosis and is resolved when the underlying cause (e.g., autoimmunity, anemia, etc.) is treated. Meaning that while ET for now does not have a cure, secondary thrombocytosis usually resolves when the cause is addressed. You cannot inherit secondary thrombocytosis, you can inherit a predisposition for the illness that, if it manifests, can lead to reactive thrombocytosis.
You can have spontaneous ET, it happens due to somatic mutations, i.e., mutations acquired during lifetime, e.g. driver mutations like canonical JAK2, CALR or MPL, or some non-canonical somatic mutations of same genes and other genes too. See linked papers.
Some people have germline mutations, which means they have inherited these genes and like any inherited gene, these mutations are present in their genome (and are incorporated into the DNA of every cell in the body) as they were passed on by a parent. There are more explanations in the studies I linked here.
Regarding the benign/malign dichotomy, if thrombocytes have been high for years and other causes are excluded, then bone marrow biopsy and NGS testing are important to assess cause of thrombocytosis, as ET is suspected.
Secondary thrombocytosis is benign.
Primary thrombocytosis or essential thrombocythemia, as it is linked to the bone marrow overproduction of platelets that is not due to other illness or other factors that, if treated, results in resolve, cannot be seen as "benign." And if malign or benign for you means either thrombosis/bleeding or transformation in myelofibrosis or AML, know that essential thrombocythemia is classified by World Health Organisation as a chronic blood cancer. The bone marrow, due to identified or yet to be identified pathogenic mutations, overproduces thrombocytes. The moment the disease manifest itself via higher than normal levels of platelets that is constant over time and not due to other illnesses of factors, than it is not benign.
If by benign you mean that someone carries the gene but does not manifest the illness, that is beyond the discussion as when thrombocytes are higher than normal, it doesn't really apply.
Also, note that hereditary thrombocytosis might not have the same bone marrow characteristics as spontaneous ET, or the same prognosis or response to treatment. Transformation into AML seems rare in hereditary thrombocythemia, depending on the germline mutation causing it, especially if other mutations are not acquired over time.
You can read the papers I appended. Hereditary thrombocytosis is straightforward to assess. On top of family history and a bone marrow biopsy, you need a genetic test for pathogenic mutations that can cause ET not only on bone marrow/blood, but also a genetic test on other cells in the body than blood or BMB (e.g., cheek swab). This and a check of TPO levels in the blood. You have this information here:onlinelibrary.wiley.com/doi...
For people with triple negative ET, studies indicate specialists should use a broader genetic testing including newer non-canonical mutations that were shown as pathogenic. The studies I linked present some of those mutations.
6 years ago I would have qualified as triple negative ET, but scientific progress helped with having a correctly identified genetic mutation, which also confirmed what was already suspected: that it is very likely my ET was actually hereditary thrombocytosis. If two or three generations in the same family have high thrombocytes, then it is time to investigate what pathogenic mutations they have and if they fit in the HT category. Genetic databases of pathogenic mutations help guide that.
Thanks, I’m familiar with all this info. However, germline mutations that cause mildly elevated platelets are, in the majority of cases, benign, meaning they do not increase the risk of transformation to MF or AML. This only happens in rare cases, around the same frequency as the normal population.
Again, once the disease manifests itself by overproduction of platelets, one is not anymore in the territory of benign. Not by WHO definition of it. Primary thrombocytosis, whether ET or HT, is classified as a chronic blood cancer. And there is so little long term research on most of the the germline mutations associated with HT, especially since some of them have been discovered or associated with HT recently, that it is wishful thinking that they are somewhat milder than somatic mutations that have a broader population and some have almost 2 decades of research behind. I am very realistic about this as we are just at the beginning of the research on HT and this means little reliable information. It might turn out to be the same, or worse or better than ET, but right now it is nothing but a guess. Only long-term studies and larger samples can tell.
Understood, but little research also does not immediately imply a conclusion. One of the links you posted specifically clarifies that HT/FT is “devoid” of risk of AML and MF. I am happy to agree to disagree.
As a trained scientist, I am aware of how studies can make bombastic claims without having the sufficient data to support them. That study is one. Science is self-correcting, so that "devoid" of risk for transformation assessment is not written in stone. Probably will change as we get more accurate estimates for the many germline mutations. There is quite some heterogeneity in genes causing HT, if you blend them, you miss important information. And it is quite funny they went to such extent words-wise, when being more cautious given the little information we have is wiser.As my dad passed away from high-risk myelofibrosis and was suspected for a while of AML, while having HT, reality matters more than what an optimistic researcher said in a study that doesn't use or refer to large enough samples to draw such a conclusion.
As a PhD in Biochemistry and Molecular Biology, I appreciate the discussion on the literature. Sorry to hear about your father. Best of luck to you and your family.
Many of us have PhDs, illness does not discriminate. Having these skills benefits not only us, but also others, as information exchange can also increase knowledge and progress in MPN research.
Regarding my being careful regarding overoptimism of researchers declaring HT is "devoid" of risk of transformation, it is based on simple understanding of bias.
Most studies on HT are on small samples of patients, either on a specific mutation in a particular geographical area, or on a potpourri of non-canonical mutations, with patients often significantly younger than ET counterparts, as seen in this table. HT tends to be identified more often in young patients, and that makes the average age significantly lower than in conventional ET samples. The risk of transformation increases with age, and when comparing a quite young HT sample with a median age of 20 with conventional ET samples with median age of 69/70, you are comparing apples with oranges. And these are just several examples of issues that represent serious limitations that do not allow a conclusion that HT does not have a risk of transformation into MF/AML. The conclusion is that it seems to be so in those specific samples, with the caveat that people in those samples tend to be rather young.
There are studies out there on a specific mutation that causes HT and the results show both thrombosis and progression happen even in younger patients. But the sample is rather small, and I would take the results with a large pinch of salt. Results seem sample dependent.
"The same mutation was identified in eight Italian families with HT. Fifteen out of 41 affected members underwent major thrombotic complications ranging from cerebrovascular accidents, myocardial infarction, deep vein thrombosis, Budd–Chiari syndrome, and fetal loss along with splenomegaly, progression into bone marrow fibrosis and overall reduced life expectancy. The MPLS505N mutation identified in the eight Italian families with HT is likely to have arisen due to a founder effect."
Another issue that makes me careful with overgeneralised predictions regarding HT and progression comes from the fact that some of the non-canonical mutations behind HT are not gain-of-function, as most mutations in MPNs are, but heterozygous loss-of-function mutations that result in thrombocytosis via different mechanisms. MPL R102C and R102P are such mutations. Studies are just starting to explore these mutations.
This is food for thought.
Table 1.
Comparison of MPL-mutated FT cohort with two MPL-mutated ET cohorts
There's a lot of different things that can impact our platelets and platelets tend to fluctuate. Infections, inflammation, injuries, smoking and even stress can raise platelets. Reactive thrombocytosis is far more common than ET (Essential Thrombocythemia), which is a rare disease.
If you are someone who menstruates, that can also elevate platelets temporarily. My platelets are always higher when I'm on my period and I try not to get my blood drawn when I'm on my period for that reason.
Some people also just have slightly elevated platelets. My understanding is that as long as your counts remain stable and there's nothing else in your labwork to cause concern, it may just be that your platelets naturally sit around the 450 mark.
I live in the US and the normal range at my lab is 450 and below. Your most recent platelets are not very far out of the normal range. How often do you get your blood checked? How many years of labwork do you have showing rising platelets?
If you are concerned, you could ask for a second opinion from another doctor. Getting tested for an MPN involves blood tests to check for driver mutations and a bone marrow biopsy. But it might make more sense to explore other more common causes first.
Hello and welcome to the forum. The good news is that you may not need to spend much time here.
Different labs use different reference ranges. This has little to do with the diagnostic criteria for ET, which include PTL > 450. It is important to note that PLT can vary by as much as 100K in a single day based on what is going on in the body. This is normal body function. There are a number of things that can cause PLT to elevate as our friend brightlys indicates.
If you find that your PLT is consistently over 450K, then a follow up assessment would be warranted. The first step is often to do a myeloid panel that includes testing for the three MPN driver mutations, JAK2, CALR, and MPL. This can be done with a simple blood test.
Given that your PLT is only borderline, it is unlikely for you to flag as a major concern for MPN in the absence of other concerning symptoms such as thrombosis, hemorrhage, or splenomegaly. The most likely plan would be to just monitor and follow up as needed. If you find yourself continuing to worry, you could look into further assessment; however, recommend not consulting Dr. Google. He is a terrible diagnostician!
Firstly my advice would be to live your life to the full as you are in the best years of your life so try not to worry unnecessarily so. Follow your doctors advise and if it helps keep an eye on platelet levels if it concerns you, however I suspect that many reading your concerns would very much like to be at your levels. I hope all the posts you read will re-assure you and help with any fears you might have. The more I learn about blood the more I am amazed how the body works and how medical science has progressed. I hope you are feeling well otherwise, good luck xx
My daughter( then 17), was found to have platelets in the high 600s about 3 years ago.
It then transpired that her platelets had been at that level when she’d had a blood test aged 12 but no-one had noted it then (think they assumed it was reactive).
She was referred to a MPN specialist, all the known drivers are negative. Had a BM biopsy which may need repeating in the future.
She now has annual blood tests and telephone review as she is well in herself. No treatment atm.
She has been advised that she will need to liaise with her team should she wish to have a baby or op etc in the future due to the possibility of increased clotting risks.
Apart from this she is great health and she seems to take it all in her stride.
I wouldn’t worry as others have said you seem to be fairly borderline and I’m sure they’ll keep an eye on you now.
Your story reminds me a lot of what happened to me in my 20s.
My platelets have never been under 420000 (420 using the same scale as you). Even during childhood. My dad also had platelets elevated, so did his mom. Doctors explained away not only high platelets, but also symptoms in my granny and my dad.
As it turns out, I have hereditary thrombocytosis. Inherited it from my dad, who inherited it from his mom.
My higher than normal levels of platelets were explained away as caused by menstruation, which is hilarious when thinking that ET can often cause heavy menstruation. Then they were explained away as due to stress, although I did not experience any sort of persistent or high stress. And despite all myths, stress does not increase platelets more than ~10000 (10 in the scale you used). Maybe severe stress would increase platelets just a bit more, but one would know about being under severe stress.
The constant explaining away in childhood was that I had low ferritin. Granny endured the same type of explaining away. So both her and I had years of having to take ferritin, while platelets remained high. She died undiagnosed, I was finally diagnosed in 2020, after years of efforts to get an adequate answer.
Not having life-threatening symptoms or heavy symptoms does not mean one should leave an issue unsolved.
ET needs to be diagnosed and monitored well before it becomes life threatening.
Also, as ET increases the chance of thrombosis, one should have it diagnosed early on, as there are many aspects of life that can be approached with much more care and allow one to be safe, such as choosing the method of contraception, as some birth control increases the risk for blood clots too, knowing about ET while planning for a pregnancy, as ET is linked to pregnancy complications, knowing about ET if one needs surgery, etc.
And PubMed is my favourite for checking medical information. It is a bit on the nose to say to patients not to use Dr. Google when in rare diseases about which most physicians do not know most patients need to get informed about their illness and need to read latest research to improve their chances of getting adequate diagnosis and treatment.
Knowledge is power, you know you body better than anyone, and doctors tend to be dismissive. So if you have the energy and the support, go investigate this further. Ask for a broad panel of genetic testing for pathogenic mutations, as there are so many new pathogenic mutations added these days, including non-canonical mutations.
I had both episodes of clotting and bleeding well before my diagnosis, they were explained away as I was so young and they were seen as too small to care about, I had a nightmare experience due to some weird clotting caused by taking birth control pills, explained away, and got a diagnosis of hereditary thrombocytosis after years of efforts.
Hopefully, your elevated platelets are just temporary, but it is always better to know and prevent than let things go too far.
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