Hey everyone sorry for such a long message. I'm a 28M and have had consistent high RBC, HGB, HCT counts for about 8 years now. The numbers though are ever so slightly elevated and range from (5.9-6.1 RBC), (16.7-17.2HGB),and(49-50.4 HCT) during those 8 years they each either went up or down and did NOT increase year after year. For example this year my RBC,HGB,HCT all went down a few ticks compared to last year .
If this was primary PV wouldn't my counts steadily increase year over year and not go up and down randomly?
My 2nd question pertains to my Jak2 test I got done in 2019. All the mutations came back not detected(no detection of JAK2 617 or 12, no detection of CALR9, no detection of ex10 MPL) which was a relief . However when I read the lab interpretation I see
"No mutations were detected in 617 or 12 of JAK2. No mutations were detected in ex9 of CALR. No mutations were detected in ex10 (505 and 515) of MPL. No mutations detected ex 14 ans 17 of CSF3A. Insertions of up to 30bp and deletions of up to 52bp have been successful detected by the assay"
What does that insertions of 30bp and deletions of 52bp mean? Is this a bad thing?
I just want to add that it seems I'm more likely secondary and not pv cancer. Not sure secondary cause . After the Jak2 came back negative my doctor doesn't seem as alarmed anymore. I have 0 symptoms of anything. I'm guessing maybe hydration since I do a poor job hydrating sometimes or asthma maybe?
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Suggest you ask one of your doctors for an erythropoietin blood test. It's inexpensive. A low numerical test result (2-5) suggests primary PV. A high test result (around 8-18) suggests secondary PV.
The Jak2v617 blood test is not foolproof. Sometimes false negatives happen...happened to me and delayed my by diagnosis, bone marrow biopsy and drug treatment (Pegasys interferon) for PV by a whole year.
Unlike you, I had symptoms of thickened blood so was able to persuade (a year later) my hematologist to prescribe a bone marrow biopsy despite the negative Jak2 blood test result. The BMB found I was actually Jak2 positive with an allele burden of 36%.
I also suggest watching your WBC count on your CBC's. If your WBC is tending to stay at the top of the normal range (10-11) that's a sign you might be progressing towards primary PV. If and when you are ever diagnosed with primary PV, suggest you get on interferon right away because when started very early, there is a good chance that low doses that have few, if any, side effects will quickly revert your primary PV to a state of Minimal Residual Disease and probably keep it there for decades if you continue to take a small monthly disease maintenance dose. Here is Dr. Hasselbalch emphasizing the benefits of starting low dose interferon immunotherapy soon after being diagnosed: youtu.be/TIlzFKLtj0k
Thanks for the help. My doctor currently believes it's secondary perhaps related to my Asthama or even hydration issues .
I will get my EPO checked. I'll bring it up to my PCP next week during my visit. Thankfully my WBC aren't towards the upper range and neither are my platelets . Currently my WBC are varying around 5.5-6.5 while platelets have gone down the past couple years from around 320 to now 294. Hopefully this is all secondary 🙏
Sorry to hear that you have the medical anxiety. A finding of erythrocytosis could certainly stir these feelings up.
The statement "Insertions of up to 30bp and deletions of up to 52bp have been successful detected by the assay" is not something to worry about. It is a statement about the sensitivity of this assay. Insertions and deletions are two types of potential mutations, also known as frameshift mutations. In these mutations there is alteration in the normal sequence of base pairs that make up the genome.
It is possible to have a triple-negative PV. The diagnosis would require a bone marrow biopsy to meet criteria for hypercellularity. Given that you have a known cause of secondary polycythemia, asthma, it seems unlikely that a BMB would be performed. Note that anything that can cause hypoxia will trigger the body to increase production of erythrocytes. This is normal. Hypoxia causes the release of erythropoietin (EPO), which is the trigger to make RBCs. If your EPO test shows EPO on the high side, as would be expected in the presence of asthma-induced hypoxia, that would be evidence of secondary polycythemia. If your EPO was on the low side and you had erythrocytosis, that would be evidence of PV.
Suggest you follow up with your care team for a more detailed explanation of all of your test results to put your mind at ease.
Thank you. My asthma isn't severe but I do take inhaler treatments seasonally as needed so perhaps that could cause minor elevations.
I have a check up with my PCP next week. I'll ask about the EPO test. Hope that comes back normal or higher side and then that pretty much may confirm secondary
Sounds like a good plan. You definitely want to know your EPO level.
The diagnostic criteria for PV are all 3 major Criteria or two major and one minor criteria.
Major criteria
1. Hemoglobin > 16.5 g/dL(men) Hemoglobin > 16.0 g/dL (women) or hematocrit > 49% (men) Hematocrit > 48% (women) or increased red cell mass (RCM)c
2. BM biopsy showing hypercellularity for age with trilineage growth (panmyelosis) including prominent erythroid, granulocytic and megakaryocytic proliferation with pleomorphic, mature megakaryocytes (differences in size)
Now, since I tested Jak2 617 and Jak2 ex12 negative in 2019 is that something that should be retested every so many years? or is a one time Jak2 test sufficient?
According to those criteria, if I do show high or normal high EPO then I can cross off primary PV as the culprit.
Thank you. Sorry for the million questions . Thankfully my counts seem to be steady the past 8+ years. Some years they tick up slightly some years they tick down slightly . In fact in my 2024 labs they are all the lowest or close to lowest levels they've been in those 8 years (5.9 RBC, 16.7 HGB, 49.8. HCT) all with no treatment. Based on that is their any indication one way or the other what that means?
If I am understanding your last comment correctly, my original jak2 was negative, If I wanted to do it again and that was negative as well as a high or high normal EPO then that pretty much confirms secondary and not primary?
Bear in mind that it is normal for these blood cell values to fluctuate based on what is going on in your body. You are correct that if your JAK2 remains negative and your EPO is high or high-normal then secondary polycythemia is the most likely diagnosis.
The best thing to do is to review your case with a MPN Specialist. This will provide the most informed opinion and relieve your concerns. Here is a list. mpnforum.com/tsr-the-list/
Just adding on, it appears after reading some of your profile that you have the same genetic condition I do NF1. Thankfully my NF1 has always been extremely mild and have no major issues from it. Apparently most major issues from it usually happen during puberty. I've thankfully almost made it to 30 problem free with regards to NF1. Being Jak2 negative but still having slightly high HCT HGB and RBC I wonder if that still plays a role
You are part a a very small group of people with both the JAK and germline NF1 mutations. Like you the NF1 variant I have has had a very mild presentation. The only significant impact has been a NF1-related brain tumor that was found and resected when I was age 63. The risk of a glioma persists throughout our lifespan with Neurofibromatosis Type 1. You are correct that many of the more severe manifestations associated with NF1 would have manifested earlier in life; however, there are issues that can manifest later in life. My brother developed a high-grade Non-Hodgkin's B-Cell lymphoma in his 60s. My sister developed osteoporosis in her 60s. It speaks to the importance of being followed by a NF specialist even in mild cases.
Regarding the interface between NF1 and JAK2, there are some but they are not well understood. The database is just too small. Both mutations increase our risk of secondary cancers. The NF1 mutation is a known non-driver mutation for MPNs that increases risk of progression into AML. Note that there is a finding that 16% of people with PV have a somatic NF1 mutation. It is the same gene but since it is somatic it does not cause the Neurofibromatosis symptoms that the germline mutation causes.
The NF1 germline mutation is associated with some hematologic malignancies. The best known is JMML, which is a type pf MPN that is caused directly by the NF1 mutation. There is some data on the link to hematologic malignancies. here are a couple of examples.
Given your profile, it is all the more imperative that you follow up with a MPN Specialist. You also need to be followed by a NF Specialist. I ignored the NF for many years until I found that I had an adult pilocytic astrocytoma growing in my brain. I no longer take the NF for granted. Likewise with the MPN. Even though I have an indolent presentation of PV, I cannot afford to take it for granted. Ignoring either condition could have very negative impact on my health. On the other hand, managing these conditions effectively allows me to live a high quality of life and I can anticipate a normal lifespan.
In the best possible arraignment, you would see be a MPN Specialist and a NF Specialist who work in the same intuition. This is usually in a major hospital system that is also a research carter. I base my specialty care out of Johns Hopkins, which is also where I had the brain surgery. There is no question that I benefit from the ease of collaboration on my care team.
Here are some links that may help you crosswalk your care needs.
Jury is still out on the Jak mutation . When I had it done in 2019 it was negative for v617 and 12, planning to do it again though just to put my anxiety at ease. But if that's the case I just have the NF1 but Jak2 Negative
Hunter - please may I benefit from your experience again?
My grandmother had neurofibrosarcoma (which I know is different from NF1 but sometimes linked?) Her children haven’t shown signs of NF1 (into older age).
I mentioned it in passing to the stroke consultant and (general) haematology; neither made a connection but I don’t know if they would have reason to. Any advice? If it’s worth raising again I’m not sure whether is an MPN specialist question (I don’t have direct access to one at the moment)? Thanks
A neurofibrosarcoma is also known as a Malignant Peripheral Nerve Sheath Tumor (MPNST). MPNSTs are a known risk with NF1. These tumors are neurofibromas that turn malignant. Unfortunately, they are a potentially fatal complication of NF1.
People can develop these tumors in the absence of having NF1; however people with NF1 have a poorer prognosis. Presumably, your grandmother would have been checked for the NF1 gene mutation when she was diagnosed. The NF1 gene marker was identified back in the 1990s. There are other common signs of NF1, the most common being cafe au let macules. In the absence of clear indications of NF1 in your grandmother or any of her descendants nyulangone.org/conditions/n... , I think it is reasonable to assume that NF1 is not present.
While NF1 may not be an issue, I would stay mindful of a family history of a serious cancer. The possible genetic predisposition to cancer in the context of having a MPN is a consideration in treatment planning. At a minimum, always following the monitoring protocols for the more common cancer risks (colon, breast, prostate, etc.) is indicated. Checking out any anomalous lumps would also be a good idea. It might also be a consideration in when to initiate MPN treatment with the intent of reducing risk of progression. This is part of why I started on the interferons. Parenthetically, a side benefit of the interferons for me is that they have shown some efficacy in treating the type of brain tumor (pilocytic astrocytoma) that I had removed. In the context of NF1, these tumors have a high probability of recurrence. I have no way to know if Besremi is working in that regard, but at 4.5 years out from the surgery, there is no sign of rumor recurrence.
Thanks so much Hunter for taking the time and explaining clearly. It all helps. My grandmother’s case was in the early 1980s, so no genetic testing. My mother doesn’t remember her having any obvious signs of NF1 so she may have had a sporadic sarcoma. (Her work exposed her to solvents and I always wondered if they played any part).
Very glad you remain tumour free. Whether due to Besremi or other factors, long may it last. You’ve had more than your share of challenges. Thank you again.
I'm a case study of strange EPO levels. I have PV and EPO was slightly low at Dx, quite common. But it's now over range and rising. As Hunter says this is most often 2ndary polycythemia. But I don't fit that and my autoimmune disease is not associated with that.
So at least for this 1 patient, high EPO would not prelude PV.
On the Jak2 test, some tests are more sensitive than others. So you could ask about this if you get another test. A lower test limit currently is ~0.01-0.1 % with ddPCR method.
Jak2 allele can increase with age, so if you're concerned periodic tests could be reassuring.
But with all that your case doesn't look PV like. For your blood tests, be sure to drink water adequately in the 20-45 minutes prior to the test. I often forget.
Looks like my Jak2 test from 2019 was 5% PCR . I'll ask my doc again to double check again this year and for an EPO to hopefully put my mind at ease even if this doesn't look that bad or PV like .
A 5% limit that could miss relevant Jak2 allele levels, although PV is more often much higher (~30-60% is common with 90+ % known). It may be good to get the more sensitive test for reassurance.
I have Jak2, started at 14% and latest was 5% after IFN (Besremi) and Jakafi (Rux) therapy. My MPN is ET like while my Dx is PV. One use of the more sensitive test is to measure the benefit of therapy in reducing the mutation (VAF)% For a select few pts higher levels can get to "not detected" after therapy, but the 5% test would not suit this purpose.
Even if you find PV at some point, it is for most not a large burden, esp with benign symptoms like yours and worst case a very low VAF that should be reducible with therapy if desired. I acquired an evil autoimmune after my PV Dx and there is no comparison vs my typical type PV experience.
Another item to know, if you do find possible PV, treatments are improving as with many diseases and at your age you would benefit well from these. But they are quite good right now too.
I'll ask about the ddPCR. However if that's not possible is a rerun of the 5% sensitivity test okay again being 5 years later?
It's good to see all these improving treatments and clinical trials especially with all the easier less dangerous methods as if I did need therapy I would not want to touch hydroxyurea at all being a chemo drug and having risky effects and me having a higher risk due to outside genetic factors . It doesn't appear that I would have primary PV but I do want to know for certain so I'll do the EPO and Jak2 again to better put this to rest.
We can only provide informed amateur opinions, you and your Dr will make the decisions.
But the forum does provide a great source for questions to ask.
Redoing the 5% test would still offer info, whether your mutation, if any, has increased over that limit. The more sensitive test is routine from most providers, so you should have access if your Dr is cooperative. One exception seems to be Canada, we hear of more hassles there getting certain care.
I've been on all three of the common MPN drug treatments. None are free of risk, but among them are good solutions for nearly every PV pt.
My guess is that the last sentence is just about the sensitivity of their assay, i.e. it is capable of detecting insertions of up to 30bp and deletions of up to 52bp. In that case it would not be specific to your test result. That's a guess.
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