Dx of ET vs PV

[EPguy]

Some of this is likely redundant, but we have many posts on this subject and plenty of curiosity. Here is a bit more, as always no single report is the last word:

The most interesting finding is that RBC, a measure we all get in our CBC, FBC, can distinguish Jak2 ET and PV when marrow points to an MPN. A normal RBC defines ET while high RBC defines PV.

"A typical MPN bone marrow histology, erythrocytes (RBC) above 5.8 × 10 12 /L in males and 5.6 × 10 12 /l in females (normal cut-off value is 5.5 × 1012 /L in females) separates overt and masked PV from ET and prodromal (early) PV obviating the need of RCM measurement"

Note they do not consider EPO nor allele burden to be criteria. The EPO finding is in contrast with WHO 2016.

From "Increased Erythrocyte Count on Top of Bone Marrow Histology but not Serum EPO Level or JAK2 Mutation Load Discriminates between JAK2V617F Mutated Essential Thrombocythemia and Polycythemia Vera"

researchgate.net/profile/Ja...

This report cites the Silver MPN group promoting use of RBC and/or RCM (rarely used today) to Dx ET/PV. Silver group was an early promoter of IFN so their opinions may be worth attention.

ncbi.nlm.nih.gov/pmc/articl...

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Some further less easy to read details:

From one source a few less known criteria that are relevant to ET (items that are more than "may be"):

BMB results:

-Approximately 90% of patients with essential thrombocytosis show an increase in bone marrow cellularity (other reports have this less often)

-Megakaryocytic hyperplasia is common (Excess megakaryocytes)

-Giant megakaryocytes are often observed; clusters of megakaryocytes may be present; significant dysplasia of the megakaryocytes is unusual (Dysplasia seems to associate with MDS)

-Bone marrow reticulin is usually increased, (this "usually" is more often than some other reports) but collagen fibrosis is uncommon.

Blood counts:

-a ferritin level that is within the reference range or increased, along with an RBC mean corpuscular volume (MCV) that is within the reference range, is sufficient to exclude reactive thrombocytosis secondary to iron deficiency and the possibility of polycythemia vera masked by iron deficiency. (I think this may relate to the straight RBC criteria in the 1st reference above)

emedicine.medscape.com/arti...

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I had normal RBC at Dx by these definitions, and my ET/PV mixed Dx. Any members are welcome to comment on their fit here.

[Wewo01]

Thanks for this information!

[Jelbea]

Thanks for posting although my ageing brain finds it hard to work it all out.

My question really is when I was diagnosed I must have had a high RBC - I do not have the report. Can one have just one raised RBC? The reason I am asking is that when the blood was taken for by Jak2 testing I was in hospital after an horrific reaction to AstraZeneca vaccine. I have never had a raised RBC since diagnosis 18 months ago.

Could the raised RBC have been something to do with the vaccine reaction? I know you probably could not answer this but I have often wondered. In the end it probably makes no difference to an 80 yo. So little was explained to me at the time. It was almost like someone here said recently - I was told I had it and handed the MPN booklet and told to read about it and not to take fortified breakfast cereals. That was about it.

[EPguy in reply to Jelbea]

Your point on a short term (acute, transient etc) increase is of interest to me also. It is near certain that a whole body reaction that sends you to the hospital will mess with blood counts in some way. Exactly what way is a harder question.

I had increased everything at Dx but in the next month all went down fast other than PLT. My Dr said the aspirin I started would not do that. I think my long covid had something to do with it, similar like your shot reaction.

On the AZ vax, it seems the tech used in that, and same in the J&J shot, (adenovirus) is no longer first line anywhere as it was higher risk, esp for messing with platelets.

[Jelbea]

Thank you so much for your reply. Up until I had the vaccine I just had a slight rise in platelets - not even up to 500 - and I have often thought the AZ did really mess about my blood result. Neither of us will ever know the answer but it does seem suspicious.

[patriciapugliese in reply to Jelbea]

I was diagnosed with ET shortly after receiving the 2nd dose of Pfizer in my mind I believe this caused my problems. Doc says no

[EPguy in reply to patriciapugliese]

I agree with Dr in his case, the vax can do a lot of things but marrow malfunction is very unlikely. But it could have brought out the effects of the ET more quickly. This happened to me with Covid, I got the original in early 2020 and that cooked along with the festering MPN to bring me to Dr and get my Dx.

[Jelbea in reply to patriciapugliese]

I had raised platelets for two years and only after four blood clots did my (now ex GP) decide he should investigate this. In actual fact he FORGOT to request an appointment and six months later after AZ vaccine my condition was diagnosed. I had just raised platelets until that time and I truly believe AZ vaccine made things much worse. I know it did not cause ET but it certainly made things happen more quickly together with the negligence of my GP delaying tests by six months. Good wishes

[MaggieSylvie in reply to Jelbea]

That's interesting. I didn't make the connection but after I had AZ, I experienced my platelets falling to within range - so good. I now have pain, so with inflammation, I wouldn't be surprised if they rise again.

[Jelbea in reply to MaggieSylvie]

Hi MaggieS - I certainly feel the AZ vaccine did me harm. I developed all the symptoms which made the powers that be say younger people should not be given AZ. I had a horrendous headache, was rushed into hospital as it was thought I was developing a stroke, had a brain scan which was fortunately clear. I feel if I had not already been taking blood thinning medication I probably would have died. Certainly it was taken very seriously by the hospital doctors.. Incidentally I suffer neuropathy/erythromelalgia and after Pfizer vaccines I have always had a flare-up of neurological symptoms which I think is common.

[EPguy in reply to Jelbea]

If/when the Novavax is avail to us, it is worth considering. It works in a more conventional way and should have at least "different" side effects. I would like to get it but will settle for the bivalent mRNA one now on offer.

[MaggieSylvie in reply to Jelbea]

I always had Pfizer up to that point, and virtually no problems. They are calling me for my fifth injection now and I hope I don't get AZ again. I have better things to do than lie around all day after a simple vaccination.

[EPguy in reply to MaggieSylvie]

Good to know there's one that works for you. I'm fairly sure AZ is no longer offered, similar as J&J in US. Will be surprising if they do offer it.

[AndyKay]

Thank you for the explanation.

[ritaandscooter1]

Hi EPguy,

There are many articles such as the ones you've posted regarding how to

[ritaandscooter1 in reply to ritaandscooter1]

To finish what I prematurely posted above..........There are many articles that point to specific guidelines for distinguishing between PV/ET. I think it's very important to realize that our MPN Dx does not always present like the guidelines would suggest. Once again we all present completely different. I initially was Dx with high platelets (ET) only, but slowly my white blood cells increased with time but my RBC's have always been somewhat in range after 18 years. The RBC count has never been high but both PLT and WBC counts have been on the high end. It's interesting that they rarely mention the WBC's as being an indicator of PV. My Dx changed to PV when my WBC counts increased along with rising HCT numbers. My Hb has always been low. I don't present like a lot of these diagnostic guidelines. Just food for thought. Does anyone else present with high platelets & WBC's but not RBC's and is diagnosed with PV? Kerry

[EPguy in reply to ritaandscooter1]

You're right about WBC and PV. WBC is increasingly considered an important risk factor, along with HCT and generally more so than PLT. One thing on that I can't find is whether that WBC risk is fixed at Dx or is it lowered with reduced WBC on therapy as with HCT.

For RCB, I was hoping to hear from any members whether the RBC idea in these reports makes any sense. It's the 1st I've heard of this simple correlation. I think the idea it's a proxy for the old RCM measure that was a Dx standard but is no longer easily available.

RBC would normally rise along with the HCT at the time of your PV Dx since HCT is a multiple of RBC and MCV. Do you have the RBC value at the time the high HCT occurred? I had HCT just barely over 50 while RBC was in range.

I agree Dx criteria are hopelessly confusing, I still can't figure mine. The standard is supposed to be BMB per WHO 2016 with related clinical data.

[ritaandscooter1 in reply to EPguy]

My HCT at the time of Dx was not high, just the platelets (800 when dx) The WBC, HCT and platelets slowly creeped up but not the RBC count. My RBC count has essentially stayed the same for over a span of 18 years at 6.0 with a range of 3.50-5.40. Its a bit out of range but has never gone up more. My RBC count does NOT rise along with the HCT rising. The RBC criteria definitely does not apply to my specific diagnose as PV. Perhaps, in most PV diagnosed the RBC counts are high. I don't fit that specific criteria and never have. Oh, and my MCV counts are always on the very low side when HCT is high but I also have low iron which affects the MCV. Like I said we all present slightly different. Have a good day. Kerry

[EPguy in reply to ritaandscooter1]

Thanks for the details. I'm not assuming this RBC Dx idea is the answer, but it is interesting. Your RBC (>5.6) does match PV according to the scale they propose in the report.

If your RBC and HCT don't move together then your MCV is changing. My Dr doesn't care for HCT since he correctly notes it's just a calculated value, (RBC*MCV) vs Hb and RBC which are measured.

[ritaandscooter1 in reply to EPguy]

In reference to the RBC and HCT not moving together then your MCV is changing. My MCV has been the same number for as long as I can remember. Be careful not to hang your hat on a lot of these proposed theories of what blood counts should or should not be and what that means and really listen to what you think your body needs. Doctors are trained to interpret these numbers which they should.

Example: My hematologist was sure that I was probably progressing because my HCT was not rising like it normally would. In other-wards I didn't need a phlebotomy for 5 months. My husband and I both knew it most likely was low iron so started taking iron tablets before the next blood draw. The iron jump started my bone marrow and HCT went back up. BMB came back excellent and mystery was solved. In other-wards there is so much the doctors don't know yet despite all these studies. Live your life fully everyday, don't attempt to get the right answers for everything to do with this disease. My own son who is a doctor (Radiologist) although very smart with what he is trained to do, freaks out when he sees my blood counts! Hes just not familiar enough with PV and MPN's. Kerry

[EPguy in reply to ritaandscooter1]

I'm near clueless about iron in our MPNs. So you're right I have nothing to offer there. Hunter is a member who understands it well.

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On the RBC, HCT, this is normally a simple arithmetic calculation:

HCt = MCV X RBC count X 0.1

epomedicine.com/medical-stu...

According to my Dr, MCV and RBC are actual measured values in our CBC. HCT was directly manually measured in the 70's but is now normally calculated, so he's not a fan of HCT by itself. Modern HCT is thus a calculated product of RBC x MCV. My CBCs match this calc, but I do find a small tolerance error (~0.3HCT) I think could be because the RBC is not reported to enough precision in my results.

-The result of the above is if RBC stays constant while HCT changes, it is mathematically required that MCV change. But if your CBCs show a different result we can all learn from that, maybe there is a further way to relate these parameters. Is your lab maybe doing a direct HCT measurement?

[mhos61]

I was diagnosed with ET in 2016 based on raised platelets (502) and the Jak2 mutation. I had no knowledge of MPNs back then, as I’m sure most of us don’t at diagnosis.

As time went on and I became more knowledgeable on MPNs I became aware that at diagnosis my haematocrit was 47.9, and my haemoglobin 16.1 (female). Surely, EPO should have been requested; I could have been early stage PV! The thing is in away it makes no difference, as I was started on hydrea and all my counts came down. But, in all honesty, it has niggled away at me.

I have just checked my RBC at diagnosis, it was 5.2 which is within normal range.

I recently had a consultation with an MPN Specialist who I have discussed this with. She has ordered LDH, EPO and Jak2 allele percentage.

My LDH is 153, EPO 7, of course, those counts could have been affected by 6 years of treatment. Still awaiting my local hospital to organise a Jak2 allele percentage. I noticed the MPN Specialist wrote ‘MPN’ for diagnosis rather than ‘ET’ in her correspondence with the local haematologist.

[EPguy in reply to mhos61]

Your RBC matches ET by the proposed criteria in the report. So it would be accurate here if that ET Dx was. Your HCT/Hb are borderline per WHO Dx criteria.

I was in the ET category by this method, but I don't have a clear Dx, officially it is PV, so there is a conflict.

On LDH and EPO, mine were very much improved by HU, now Bes. My EPO was at or below range at Dx (depending on the ref used), LDH was quite high. So it is possible you had different values at Dx.

In a post a while I ago, I noted that EPO is often raised in ET as well, that may be why it's only a minor Dx criteria.

Your Dr's note on "MPN" is how mine described it when we 1st met.

[mhos61]

Thanks for all your analysis, particularly of graphs. I really appreciate your input. Here’s another one which may interest you.

haematologica.org/article/v...

[EPguy in reply to mhos61]

This report points to only two ways for a definitive Dx, "isotope RCM studies remain the gold standard for discriminating ETJAK2V617F from PV." and the 2nd way, a BMB. RCM is still the most established.(but no longer widely available, the chemicals they use my dr said are very expensive now)

This plot from the report shows large overlaps between ET (red), PV(blue) curves. This is the uncertainty they talk about. Unfortunately there's no such plot for RCM, if there were it seems the ET and PV curves would be entirely separated.

One nugget they don't mention seems to be for women, these criteria are not that bad, with AUCs in being much higher than for men in Table 2 (AUC closer to 1 is better)

In sum, this detailed report contravenes the Dx certainty of the one at top regarding RBC value, while continuing the pattern of BMB being the best available Dx.

Hb-RBC-HCT overlaps

[mhos61 in reply to EPguy]

Thank you, appreciated!

[PhysAssist]

Hi EPguy,

It never hurts to repeat information- that may actually help it sink in, especially if it's presented in a different format or manner.

I was confused by the part about hypercellularity of bone marrow in ET- but I have to assume that you meant it generally, and not as another specific difference between ET and PV, because for one thing, I know that it was specifically reported in my BMB as occurring a in all cell lines- not just in the megakaryocytic line.

...and: "Marrow cellularity in the diagnosis of polycythemia"

ncbi.nlm.nih.gov/pmc/articl...

"Increased marrow cellularity is well recognized in polycythemia rubra vera (PRV), but its value in the differential diagnosis of polycythemia is not always appreciated. In 28 patients who had marrow aspiration performed on account of a raised hemoglobin concentration or red blood cell count (RBC), marrow cellularity was assessed subjectively and also measured; a comparison was made with the white blood cell count (WBC), platelet count, presence of splenomegaly and plasma volume (PV). Marrow cellularity, particularly when measured was shown to be the most reliable method of making a positive diagnosis of polycythaemia vera; cellularity of greater than 75% makes it unnecessary to perform other investigations to exclude secondary erythrocytosis."

As best I can understand it, if you just have megakaryocyte hypercellularity and high platelet counts, that's pretty much ET, but if you have [as I ended up with] increased counts across the board and trilinear hypercellularity, it's PV, but that there are also a number of in-between states that could either be on their way to one of the above, or could possibly [?] be some hybridized individual version of an MPN.

I'm not sure that/if my addition is helpful, but like everyone else here, I'm just here trying to understand my disease, and to help myself and others live well despite our diagnoses.

Best,

PA

[EPguy in reply to PhysAssist]

I agree on the cellularity, tri-lineage is a near definitive PV indicator. In many BMB reports, including the sample you quote here, cellularity is not called out for which cells are increased, that is in a separate line or section. It seems they could/should specify such as "trilineage hyper-cellularity" or "megakaryocyte hypercellularity " as you described it here. But maybe they must be separated to make sense.

Much of this is still mysterious to me. I think megakaryocytes, erythrocytes, and leucocytes are equal levels in the order and comprise the tri lineage, but maybe it's a precursor to these? Are the cells of cellularity any of these 3 items?

The sample you quote "Marrow cellularity, particularly when measured was shown to be the most reliable method of making a positive diagnosis of polycythaemia vera". But when the % is lower than the 75% example it's back to the uncertainty.