Confused about diagnosis

[Blackroc]

I was diagnosed with JAK2+ MPN in August 22 as a result of abnormal routine blood tests.

I am a female aged 75. I am attending a haematologist in his rooms in a private hospital, so don’t have access to a team. The haematologist is also a consultant at ja large public hospital serving a large area in the West of Ireland.

At diagnosis my counts were: WBC 8.6 (had been 9.6 at initial consultation and slightly over normal on earlier tests ), RBC 5.1, Haemoglobin 16.9, HCT .506 and platelets 534. I was prescribed 500gm Hydroxycarbamide 4 days a week and Allopurinol. I was already on Elequis for Afib, so no Asprin.

At my next consultation the platelets had decreased to 462, but the WBC had increased to 10.3, RBC to 5.3, Haemoglobin to 17.8 and HCT to .518, so Hydroxy was increased to 9 tablets a week. He mentioned that the object of the treatment was to bring the PLT down to the 200s, to allow for an increase.

At my last consultation last week these were all within normal range as follows: WBC 8.9, RBC 4.00, Haemoglobin 14.9, HCT .429 and PLT 391. - all good news.

Prior to diagnosis I also had Erythropoietin tested which came back at 6.8, which the haematologist described as low normal.

The only diagnosis I’ve had is JAK2 MPN. When I asked which MPN I had, he told me that it was unlikely that I had MF (which my mother had had) and that it wasn’t necessary to know which I did have, as the treatment would be the same. A BMB has never been suggested.

Having read all your excellent posts for the last few months and doing some reading on the internet, I decided myself that, since my RBC, Haemaglobin and PLT were all raised at diagnosis and WBC had previously been slightly raised and my Erythropoietin was low normal, I was likely to have PV.

However, at my last consultation, the haematologist said that if the RBC ONLY had been raised, he’d have been concerned to keep the HCT below .45 and pointed to the .429 result, implying that that was not of concern in my case, since other counts had been raised. I know from reading your posts that with PV it’s important that keep the HCT below .45, so now I’m confused.

I guess my question is whether I should press for a more precise diagnosis.

Any thoughts would be greatly appreciated.

Judith

[MCW22]

Yes you absolutely should.

[Blackroc in reply to MCW22]

Thank you MCW22

[EPguy]

According to the WHO 2016 criteria, ncbi.nlm.nih.gov/pmc/articl...

Table 1

you don't entirely qualify as PV. Your Hb and HCT would get you the express route to there, (see last paragraph bottom of this table) but your normal EPO means you'd need a BMB to be sure.

On EPO, according to this and other reports, yours is quite normal, well over the 6 they consider in a normal statistical range. This report has a wealth of info on EPO levels. Common other criteria go as low as near to 4.

"Median (IQR) erythropoietin concentrations were ... 7.9 (6.0–10.6) IU/L in women."

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

--

I agree that discussion of RBC is confusing. HCT goal is usually based on the PV Dx which is lots more that just RBC. There is an older measurement of RCM (see table 1 of the WHO list) might it be this measurement he refers.

Likely most MPN Drs would call it PV anyway. But you'll need the BMB if you want a more definite answer.

Note that US and Euro have different practice in HCT goals, for female most Drs in US try to hold 42-43.

--

All things equal, a PV Dx can be advantageous regarding treatments, for example in the US it's on-label for both Besremi and Rux.

[Blackroc in reply to EPguy]

Thank you EPguy for that very helpful information. It’s good to know the EPO is not particularly low. I have a lot of reading to do. I don’t think Besremi and Rux have been approved for PV under our drugs payment scheme. Peg is used but I am nervous of interferons because, as someone who developed Coeliac disease at a later age (late 60s), I believe I am prone to develop other autoimmune conditions. I am also nervous of possible effects on eyes, having already lost the central vision in one eye and part of the vision in my other eye due to AMD.

[EPguy in reply to Blackroc]

Strangely my EPO is now a bit over range as I've posted. No useful info on that from a top specialist, seems very rare in MPN PV.

I'm totally with you on the autoimmune risk of IFN. I had no history of such risk, but you can read my posts to see that I am one of the extremely rare victims of acquiring irreversible autoimmune disease from IFN (triggered by a flu vax) This is a black box risk, the highest type in USA, for IFNs, rare but very severe. And it can happen fast.

Likewise your retina risk is a negative indicator. I got regular eye checks while on it, including after passing out and hitting my head from that last IFN dose. Strangely IFN improved my focal vision, even still so after quitting.

In contrast to IFN Rux can calm the immune system and Jak inhibitors are being used or studied for various autoimmune. So if your health system opts to cover it in the future you might discuss with your Dr (preferably MPN specialist as Hunter notes)

[Manouche in reply to EPguy]

 You wrote :« I am one of the extremely rare victims of acquiring irreversible autoimmune disease from IFN« 

Autoimmune diseases are not caused by interferon but rather by a dysregulated immune system that attacks healthy cells in the body. Interferons are proteins that are naturally produced by the body in response to viral infections and other threats. They play an important role in regulating the immune system and can be used as a treatment for some autoimmune diseases.

academic.oup.com/rheumatolo...

[EPguy in reply to Manouche]

Unfortunately for me I've been learning more than I want to know about Sjogren's and autoimmunes and am qualified to comment. Agree IFN for nearly everyone is beneficial and harmless. But that disregulated immune system can rarely get triggered ("aggravated" per Bes label) by many things such as vax, IFN...

One consistent finding is IFN, including IFN-a, can be -a- or -the- bad actor in autoimmune disease. These refer to natural IFN-a in the body. But the IFN we inject is directly implicated in the last study here.

--

More on the point is right on the Besremi label:

"Interferon alfa products may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune,..."

*All quite rare but I'm living the misery that is this label portion, and Blackroc of the top post here is wise to be cautious.

The link you have is consistent with IFN mediated (causing) immune disease. And they note treatments target (aim to reduce) IFN:

"Type I interferons play a causal role in a range of diseases, most notably in autoimmune connective tissue diseases.

Biologics that target type I interferons appear effective in SLE and are in phase III trials."

--

More samples:

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

"In pDCs from lupus patients, HCQ (Hydroxychloroquine) was able to decrease type I IFN production, probably preventing the activation of TLR7 and TLR9 receptors"

"These results suggest that IFNα and IFNλ may have a synergistic effect in the pathogenesis of SS"

"In view of the large amount of data demonstrating that IFN pathway activation plays an important role in the development and progression of the pathological process in pSS, IFNs, and namely type I IFN, have been identified as a potential target for the treatment of this disorder."

Table 2 shows some of the agents being tested to modulate (reduce) IFN.

--

Another example with PegIFN for Hep-C possibly directly implicated:

pubmed.ncbi.nlm.nih.gov/200...

"It is highly probable that interferon-alpha-induced systemic lupus erythematosus and Sjögren's syndrome in this case. Interferon-alpha might be important pathogenically in these diseases."

Of course there are countless other factors in any condition we get, and likely conflicting studies, but the pattern is clear that IFN-a can be a positively correlated factor.

--

All the above is why the experts say to quit IFN immediately upon appearance of autoimmune disease. My last dose did me in as my posts describe in detail.

In my case I believe the IFN biased me but the vaccine triggered it. My Rheum agrees with these possibilities.

[hunter5582]

Suggest that a consultation with a MPN Specialist is in order both to clarify your diagnosis and ensure that you have appropriate treatment goals. You are correct to think that your diagnosis more closely matches PV than ET. It could also be a MPN-Unclassified. A full assessment would be needed to make the determination.

It is incorrect to think that it does not matter which it is. The treatment targets for ET and PV are different even when the same medications are used. With PV, controlling the erythrocytosis is more important that controlling the thrombocytosis. There is a significantly higher risk of thrombosis when HCT > 45% males, HCT > 42/43% females. That is why these targets are set for people with PV

Having PLT targeted in the 200s for either ET or PV is not part of any treatment protocol I have seen. There is no linear relationship between risk of thrombosis and the levels you are describing. When a numeric target is used, many MPN Specialists use PLT > 400. Some use PLT < 600. Note that is does matter what your baseline level of thombocytosis is.

The benefits of cytoreduction must be balanced with the intrinsic risks of cytoreductive medications. That is why the targets matter so much. We each need to use the lowest dose possible to reach the appropriate treatment goals(s). We each need to determine what risks we are willing to take and which medication we tolerate the best. There is more than one choice.

It is worth doing whatever you need to do in order to consult with a MPN Specialist. There is only one MPN Specialist listed in Ireland, in Dublin. mpnforum.com/list-hem./ Most hematologists have very little experience managing MPNs. Optimal care is ensured by consulting with a doctor with more extensive experience and training managing MPNs.

Wishing you all the best.

[Blackroc in reply to hunter5582]

Thank you Hunter for your very helpful reply. You’ve steeled my resolve to ask for a referral for consultation to an MPN specialist.

[katiewalsh]

Hi. I realize that Dublin probably is quite a distance from you. But if there’s any way you could manage to take a trip there to be seen by the MPN specialist I think you should do it. Rarely is a doctor (who’s not a MPN specialist ) able to provide the best care in diagnosis & treatment. Ideally this MPN specialist can coordinate your future care with a hematologist near you. If there’s no way you can get to Dublin to see this specialist, you could ask your doctor if s/he will consult with the Dublin doctor about your case. I travel twice a year to see my specialist & deal with my local hematologist the rest of the time. Good luck. Please stay in touch with us. Katie

[Blackroc in reply to katiewalsh]

Thank you Katie. I think that is the way to go. I am not very mobile due to several other medical conditions, but it is doable. Judith

[Wyebird]

considering that you are paying for these consultations I’m horrified your heamo’s not answering your questions fully,

Is he an MPN specialist?

what the situation is regarding healthcare in S. Ireland . Do you always have to pay?

[Blackroc in reply to Wyebird]

I should probably be more forceful about getting clear answers. He is a very nice man but has a tendency to waffle when I ask questions and I end up being even more confused. It’s hard to know how much of a specialist he is. Ireland is a small country with a population of only 5 million and I suspect there are very few real specialists. However, I do intend contacting the only one listed on the MPN voice list to ask if she will see me. Our system is a cross between the British and US systems. In theory we are entitled to free or almost free hospital and consultant treatment but because of long waiting lists, most people who can afford it take out health insurance, which, depending on your policy, covers hospital treatment and sometimes a contribution to outpatient expenses. Drugs are not covered by insurance. People on very low incomes get them free or at nominal cost. Otherwise a family’s drug costs are capped at €80 per month, but the drug has to be approved for reimbursement.

[Exeter21]

Definitely find an MPN consultant even if only phone call consultation they are experts not Haemotology as I found out early in treatment. They are obsessed with bringing platelets to a ridiculous level even if medication makes us unwell . After consulting MPN she explained my platelets at 490 were not worrying . I am now on Interferon & still hover up to 600 but feel fine as are my blood results etc. I am ET Jak2. But it was more than worth it for me to get a phone consultation from MPN . Good luck Julia UK .

[Blackroc in reply to Exeter21]

Thank you Julia. I think you’re right.

[mhos61]

I agree with all the previous comments.

These two Specialists have been speakers at MPN Voice conferences held in the Irish Republic. I believe they’re highly rated by their patients.

Dr Clodagh Keohane, Cork Mercy Hospital and Dr Eibhlin Conneally, St James’ Hospital, Dublin.

[Blackroc in reply to mhos61]

Thank you mhos61. Dr. Conneely is the one I’m thinking of contacting. I’ve also heard good reports of Dr.Keohane.

[ainslie]

it seems like you have PV , although your counts may not have been high enough to qualify as PV using certain criteria you may have qualified a bit later if untreated and your counts rose. Your Haem is on the right track re Hct ie try and keep it down to under 45 , some say 43 for female. I am curious about his goal of 200 for platelets, usually, if you don’t have other risks expert haems are not concerned about platelets until 1 million plus, in cases when they think platelets should be lowered they tend not to aim below 400, so that appears a bit odd. As always , if any doubt try to get a second opinion ideally from MPN expert, who can then keep your local Haem on track. Hunter already gave a name of one doc, there is a good fairly famous expert Mary Macmullen (maybe spelt wrong), she is Irish but I am not sure if she lives in Ireland, you could Google her or others may chip in.

[Blackroc in reply to ainslie]

Thank you Ainslie. Dr.McMullin is in Belfast so not really an option. I heard her speak at an MPN Voice forum in Galway recently and was very impressed. I think she may also be close to retirement - at least that was the impression I got.

[ainslie in reply to Blackroc]

ah okay, yes I heard she knows her stuff.

[Meatloaf9]

I believe that most MPN specialists would recommend a BMB as part of the work up for a MPN diagnosis. My specialist when I was first diagnosed said that the BMB is diagnostic.

If you want to know, I would, it would likely be best to have the BMB. The one I had which was done by an experienced hematologist was quite simple.

Best to you in making your decision and in the future.

[Blackroc in reply to Meatloaf9]

Thank you Meatloaf9. I don’t relish the thought of a BMB, but may have to bite the bullet.

[Otterfield in reply to Blackroc]

A BMB is not pleasant but not that bad with an experienced haematologist. Say yes when gas and air is offered, it really helps. I now have to have one every three months so I promise I know what I'm talking about!

[Blackroc in reply to Otterfield]

Thanks Otterfield. That’s encouraging.

[Lappool]

I don’t know much about female RBC ranges, but isn’t 5.1 and 5.3 normal? I’m a male and have 5.4 RBC’s and my lab goes all the way up to 6.0 as normal. My labs also have HGB normal up to 18 and HCT normal up to 54%

[Blackroc in reply to Lappool]

my lab results show normal RBC as 3.8 to 4.8, HGB 12-15 ( I recall my haemo saying normal range for men was up to 17) and HCT .36 to .46. How confusing.