Looking for thoughts please.
I’ve been diagnosed with Quadruple negative thrombocytosis since 2022, started Pegasys July 24 and recently switched to Besremi 125mcg every 4 weeks. Platelets have reduced. Also on 75mg of aspirin a day.
I’ve had an automated text from my GP surgery about booking a Covid booster jab and unsure if I want to continue with these. Wondering if these were a contributing factor to my diagnosis ?
I would be grateful for any thoughts xx
I understand that you might have anxiety as you do not have yet an answer on the genetic mutation behind your illness.
Covid-19 vaccines have nothing to do with MPNs. They are actually saving the lives of people with MPNs, who are often more vulnerable to the infection and poor outcomes of infection. So the answer is simple: those vaccines did not cause your illness. MPNs existed long, long before mRNA vaccines. Before genes that cause MPNs were discovered, all MPNs were "negative" for genes, just because there was no genetic testing yet.
The most likely cause of your illness is a genetic mutation, either acquired, and this usually happens many decades before the illness manifests, or, in some cases, hereditary, meaning you inherited it from a parent. Not all genetic mutations that can cause MPNs are regularly tested and known. Some mutations are still discovered.
ashpublications.org/blood/a...
pmc.ncbi.nlm.nih.gov/articl...
ashpublications.org/bloodad...
You say that you have "quadruple negative thrombocytosis." You need to mention for what genes you have been tested. The more common expression is triple-negative MPN, expression borrowed from triple-negative breast cancer, although it is a very different thing, as in MPNs it refers to the lack of canonic mutations such as JAK2, CALR and MPL, and in breast cancer it refers to hormone receptors in the tumour.
The mutation you have might not be included in the genetic test you received. If it weren't for my luck of being tested at a hospital that does research and uses a broad genetic testing panel, the non-canonic mutation that causes my hereditary thrombocytosis wouldn't have been found and I would have been in the category of triple negative MPNs.
If your GP thinks it is time for your Covid-19 booster, it is safer to go with their suggestion, as you are a risk patient.
Thanks for your response regarding my worries about having the Covid vaccination. What you’re saying makes total sense.
It’s soo interesting to hear about possible further testing for a mutation. Something I will be curious about at my next appointment. Although I’m aware I may need to research further afield.
I’ve been tested for JAK2, CALR, MPL, BCR-ABL - all negative. I also had robotically assisted surgery to remove a 15mm lesion within my kidney last year as it was thought to be cancerous. Thankfully it turned out to be a cluster of blood vessels.
Can I ask if you are on any meds for your diagnosis please?
Thank again - so helpful
You have been through a lot recently. I hope you have a good MPN specialist who can answer your questions.
My mutation is MPL R102C. It is a germline mutation, this means I was born with it. I inherited it from my father, so my thrombocytosis is hereditary.
There is not much research on hereditary thrombocytosis, so there isn't a recommended treatment, only the mention that cytoreductive therapy (e.g., with hydroxyurea) shouldn't be used. But that comes more from the lack of studies on whether treatment used for people with acquired MPN mutations would be efficient in people with hereditary thrombocytosis.
As I am in my early 40s, the only treatment I get is 75mg of aspirin per day. My hematologist hopes that in 5 years research would have discovered much more about hereditary thrombocytosis and that there would be some sort of targeted treatment.
I hope you get your answers and a more comprehensive genetic testing. Anyway, genetic testing needs to be repeated now and again even in people who already have a detected mutation, as for acquired mutations the variant allele frequency (VAF or allele burden) can change in time, and people can also acquire some non-driver mutations that could influence prognosis and treatment choices.
Take care!
thank you TTA, your correspondence is very much appreciated and reassuring. I definitely need to be more proactive in asking my consultant questions.
I’ve refused the jab . Had 9 and none last year . Still had covid twice even with all those jabs
First, I should open by saying that I've been a scientist at NIH for a few decades and understand the value of vaccines. Volunteered to help on vaccine clinical trials being developed at NIH (not covid). And personally, I've rolled up my sleeve for more that 100 vaccines over my lifetime. Despite being very active and healthy, I unexpectedly developed an adverse reaction within two hours of the first Pfizer shot. Subsequently, I was the first in-person patient/study participant seen at NIH for a covid-19 vaccine reaction. There's not the space and time to go into details, but the experience opened my eyes to the fact that we didn't then and still don't fully understand the covid-19 vaccine. As for MPN, could the vaccine have impacted mine? Cytokines and other assessments done at NIH and elsewhere raise questions I've not yet been able to answer in my case, so I won't rule out the vaccine's possible role.
To be clear, this is not to discourage you (if you've not had a previous adverse reaction ) from getting a covid booster. Rather, I encourage this community to be receptive to learning more about the covid vaccine... immunity and more. At the very least (and I'm sure you've heard this before), increasing our knowledge of successes and failures better prepares us for future pandemics and vaccines.
All the best to you.
The fact that you had an adverse reaction to the vaccine which coloured your perception of it does not mean you have the authority to speak about such vaccines as being detrimental. Studies on mRNA vaccines included millions of people internationally and poor vaccine reactions are very few and linked to individual propensities, and were almost all linked to the first two doses of vaccines, not to booster doses. The risk for myocarditis following initial vaccination with mRNA vaccines is 0.0035%, and it happened mostly in very young people, mostly male adolescents. 3.5 in 100,000 (one hundred thousand) people had adverse reactions such as myocarditis from the vaccine. Most cases were mild.
Risk of myocarditis following SARS-COV2 infection is significantly higher: 21 out of 100,000 people had myocarditis from COVID-19, the illness. And the illness itself bring a lot of risks, including severe illness and death. It is much safer to vaccinate.
pmc.ncbi.nlm.nih.gov/articl...
We all have reactions to various things, plants, VOCs, medications, that does not mean those things are dangerous for most people. They are dangerous just for us. I could die from eating a banana, that doesn't mean that bananas cause immune issues in everyone or that bananas are behind cancer.
You are using several logical fallacies such as fake expert, appeal to authority ("NIH scientist"), appeal to fear, and appeal to ignorance ("we do not know," "be receptive to"), slippery slope and overgeneralising (you had a bad reaction - it is bad for everyone - it can cause cancer), to push distrust and fear in COVID-19 vaccines and push overall discreet antivaccine sentiments. This message in itself is disinformation. You are a sample of one who had a poor reaction to a vaccine. You are neither an expert on mRNA vaccines, nor a MPN expert.
Regarding your positioning as NIH scientist, that is appeal to authority and that does not equate to real expertise in the topics discussed. You are not MPN specialist or a researcher in how MPNs develop. For what we know, your NIH specialisation could me mental health or something that has absolutely nothing to do with MPNs. And being specialised in some area researching immunity does not equal competence in answering questions about MPN causes and development.
Your message also implies that the COVID-19 vaccines cause MPNs, which is an enormity, it shows you do not understand how MPNs happen and how many years are needed between one being exposed to a risk factor, acquiring a pathogenic mutation following said exposure, and then getting to the allele burden necessary for that MPN to manifest. You say you "know about immunity," but obviously if you "knew about immunity," you would also know that it is ridiculous to say that MPNs develop 1 - 2 years from exposure to a potential risk factor. And that mRNA vaccines are safe for the vast majority of people, thus not a risk factor.
This is fear mongering and not linked to the way MPNs actually develop. It is misinforming. This is not the first antivaccine conspiracy theory on MPN groups that claims that COVID-19 vaccines cause MPNs. I saw the same content you are pushing here pushed on other MPN support groups, only with a slightly different packaging.
MPNs have existed for a very long time, there are accounts of illness in history that match symptoms of MPNs, thus well before vaccines existed. MPNs are caused by acquired and hereditary mutations, not by vaccines. There are enough studies in the scientific literature to get a grasp on that.
What is the purpose of your spreading misinformation and fearmongering? Where are the scientific studies that support your claims? I understand that you had a bad experience during the trial phase of these vaccines, but that doesn't mean you should spread misinformation based on your personal anxieties. That would be something for you to discuss with your health care provider. You could end up influencing vulnerable people into not taking their vaccines and ending up with severe COVID-19 in the hospital.
There are thousands upon thousands of studies showing the COVID-19 vaccines are safe. Including studies on the inflammation profile, which overall seems slightly lower than other types of vaccines in the general population.
yalemedicine.org/news/covid...
And the type of inflammation needed for what you speculate could be a risk factor for acquiring mutations that could cause MPNs needs to be chronic inflammation present for many years. How can a vaccine that results in temporary inflammation lead to MPNs in just a couple of years, when autoimmune illness, in which the inflammation is very high, cannot achieve that? People with autoimmunity are more at risk for developing MPNs later in life.
There is not a single study your account points at, only your "suspicions" that happen to match most conspiracy theories against the COVID-19 vaccines.
Despite your last paragraph, in which you claim you are not saying to people not to vaccinate, you use the "but" tactics, you "encourage" people to "learn more about the COVID-19 vaccine." That is a classic tactic of antivaccine conspiracy theories, in which people are exposed to doubt about modern and more recent medical discoveries, and "encouraged" to "do their own research," which is a way to open people up to accepting misinformation.
Your post is spreading disinformation that could lead to people getting in harm's way.
Perhaps if you carefully read my remarks and you comprehended them, you could have responded with more logic, less emotion and fewer accusations.
I did my 3-year post-doc training in cancer research at the National Cancer Institute. But I didn't specialize in MPNs, so you'll arrogantly disregard that training and the relevant scientific career thereafter.
But a few other points:
You don't have knowledge about my unpublished vaccine data that's of potential relevance to my MPN sequelae. Nor do you know who else has analyzed or helped interpret the data, etc. You're uninformed.
I kept the post to my own experience. Yet you attempted to diminish that experience. I've spent 4 years pouring over covid vaccine data. Thousands of adverse reactions. But I suspect you'll discount those of others, too.
You want studies of covid vaccine adverse reactions? I'll soon attach a lengthy list of published studies.
I've been striving to increase our understanding of covid vaccines. I didn't realize you already knew everything there was to know about them.
Unpublished "research" equals a PDF on the Internet that any ativaxxer can create. Only peer-reviewed studies, especially ones that are replicated by other studies matter. Otherwise, you just speculate.
Nice try - the part speculating about my emotions. The fact that you use logical fallacies and bias and me pointing out you misinform is not being emotional. It is pointing out you speculate and misinform.
You say you have a post-doc, so you should know that unpublished data is unreliable as it did not pass peer-review.
It might be that your data is problematic or that it doesn't fulfill the quality needed for a study to be published.
Publishing in medicine is rather fast. One does not need to sit on said data for 4 years, unless one had studies rejected.
Until it gets published in a reputable scientific journal, what you claim is just a speculation.
And you do have a bias, you had side-effects from mRNA vaccines and you now cherry-pick information that confirms this bias of yours.
In science, in order to be an ethical scientist, you need to check your biases.
You will, most likely, spam me with a list of cherry-picked studies in an attempt to make your point. That doesn't make your endeavour scientific. It makes it the opposite of science.
Also, what on Earth is the concept of MPN sequelae? Are you inventing concepts? There are specific terms related to MPN. There is nothing in hematological journals with that combination referring to MPNs.
Below you have the definition of sequela in medical coding, and it is obvious it refers to acute illness, not chronic illness:
"A sequela in ICD-10 (formerly known as “late effects") is a residual or produced condition that is a direct result of a past illness or injury. This condition may be apparent in the early stages following an acute phase of an illness, or the condition may appear later."
MPNs are chronic illnesses, not acute ones.
Sequela as medical coding is used in solid cancers, you cannot just apply it to MPNs.
Please stop using appeal to authority here to push your speculations. You are using big words and claimed authority and you remind me of Wakefield and his retracted fraudulent paper that fed antivaccine conspiracy for decades now.
You and I share some experience. I'm also a tech type and was and still am a provaxxer. I had an adverse reaction to a flu vaccine that, in sequence with IFN, led to a horrific and permanent outcome. (my posts Last Dose)
Is your reaction resolved? Did you have another vaccine close in time to the one you reacted to? My lesson and advice is, if they are not same day, to space them apart by other than one week. This was part of the unlikely sequence of events that led to my outcome.
For the covid vax, if one prefers a more traditional type of vaccine, the Novavax is available. Some members on the Sjogren's forum prefer it.
I've also had run ins with member TTA here, and expect one again. I used to have a similar attitude to vax hesitation, although more understated.
--
One not-valid reason to avoid the covid or flu vax is that efficacy is not near 100%. The flu vax can be well short of that. We didn't accomplish herd immunity for covid and never had with the flu vax. But both can reduce the severity of an infection and so are worthy options. On the spectrum there are vaxes like measles, MMR that are near 100%, these are no brainers to get that got a bad rep from that bogus 1990's report.
--
As you say we await ever better vaxes, some in the works are quite promising for covid. I have been advised not to get further vaxes in light of my specific condition, so I eagerly await the next gen, maybe nasal that is in ph 1 in the US.
Thanks for your reply. I'm sorry to hear you had a reaction to the flu vaccine. I'll check your past posts.
Good points about the vaccines. After my adverse reaction to Pfizer, the thinking was that mRNA was the issue, so I tried J&J in place of my second Pfizer shot. Well, I got worse after J&J. So yes, in response to your question whether I had another vaccine close to the first covid shot - yes, apparently my covid vaccines were too close together by a month or so. It's helpful you've identified time interval as a culprit in your case. I sincerely empathize if you've had to stop all vaccines, at least for the foreseeable future. I've continued to get some vaccines, but am highly selective. to say the least, my past risk-benefit analyses have been disrupted when benefit of all vaccines outweighed my risks for me. My specialists advise against future covid v's (among current offerings) for me. Interestingly, serial SARS-CoV-2 antibody testing shows a steady increase since my covid vaxes (I've never had covid symptoms and continue to have negative nucleocapsid tests). To be clear, I don't see increasing covid antibodies as a vax substitute, just sharing info (past vax antibodies is another discussion). Flu vax became a wild card after I tried 2 subsequent years post vax injury and 2nd year resurrected various symptoms, so my specialists advise against future flu shots for me (tough on me as I had flu vaxes for 28 years in a row). While I've recovered from covid vax in many ways (with some permanent damage), future vax reactions could be more severe Pfizer/ J&J reactions. But fortunately whooping cough vax update and others went smoothly after my covid vax injury. Like you, I'm eager for the next generation of vaxes. We need more options.
That is surprising you got a similar reaction to two very different vax platforms (mRNA vs Adenovirus) and even an entirely different vax (flu vs covid). Sort of discouraging on my prospects for rechallenge.
I think your spacing was more than one week, is that right? I try to use these opportunities to suggest safest practice, which is anything other than exactly one week apart. Two weeks is a common min, and even same day is better than one week. It should be on the consent form "has it been at least two weeks since your last vaccine?" Any exceptions can be addressed there.
Seems your vaccines worked quite well, with no evidence of infection. Zero infection history by 2025 is uncommon. Maybe you also have some natural resistance helping out as in this report:
bmj.com/content/385/bmj.q1382
"The researchers said that high levels of the HLA-DQA2 gene before exposure also helped people to prevent a sustained infection from taking hold. ..People with high levels of this gene cleared the virus so effectively that they did not return a positive PCR test at all and had no symptoms"
I know some of the new vax work is going after the N protein for maybe broader protection, but some early efforts didn't work out.
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To confirm, my horrific outcome required a series of unlikely events, any one by itself is very unlikely to be a reason for my permanent damage. For example a history of severe mono (EBVirus) is a risk adder.
I just taught some people about disinformation and about the "hook" method of antivaxxers: they do not disprove all vaccines, that would make them look suspicious, but only the most recent ones, the ones with the newest technology or related to a major crisis like a pandemic, as they know that people work on anxiety.
You do exactly that. That is the entry point in antivaccine conspiracy theories. Often generalising from a poor personal experience with a vaccine, people go and preach anxiety and fear about a particular vaccine, despite science showing it is a safe vaccine in the general population. They do not accept that their very personal experience is just their experience, that they are a sample of one, and that is not how science works. Being an outlier might be tough for the individual, I get it, but spreading unnecessary anxiety and doubts to others is unethical.
You present more disinformation than I have time and energy to debunk.
A vaccine does not need to be 100% efficient to work, and you know this. This is not how prevention works. We already discussed this, yet you insist to present same disinformation again and again.
In the end, Wakefield did his fraudulent study because he wanted to discredit the MMR vaccine as he had his own separate vaccine that he wanted to push after discrediting the MMR.
I get it you are upset about your vaccine reactions. That doesn't make your spreading of vaccine disinformation on a forum for vulnerable people ethical.
Read more carefully my comment (I edited it to bold face the -not- in case that was confusing):
"One not-valid reason to avoid the covid or flu vax is that efficacy is not near 100%. " and I agree they are "worthy options" to reduce severity. But for those calling them inadequate since they cannot prevent all infection, that is not what they are for, in contrast with MMR etc.
Well said.
From my personal experience I would very much recommend getting the booster. 1,5 years after my first infection and 2,5 years after my 3rd booster I came down with a not so mild Covid infection. On my first day back at work I was admitted to hospital with stroke symptoms. It turned out I had developed a huge thrombus in my carotid artery. Particles of that went to the brain and caused the stroke. I needed two carotid surgeries and went through a long time of rehab afterwards.
What I learned from the doctors and a lot of reading in papers: Covid can cause major vascular damage leading to thrombosis. And MPN patients are at especially high risk because of our predisposition for thrombosis.
In any case its good to prevent infection.
The jabs certainly do not offer 100% safety but protect from severe infection. I only had mRNA jabs up to now and experienced no side effects. But there are also effective alternatives such as the Novavax vaccine.
Hi, I thought I had replied earlier, but it seems to have vanished.
Maybe this paper will answer some of your concerns. pmc.ncbi.nlm.nih.gov/articl...
Hope it helps.
Several comments: the authors of the paper are from the "Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona". Osteopathy is considered pseudoscience. So the source is not of high trust.
Also, their title is bombastic and misleading and not a good reflection of what the text actually says.
That paper just says that in patients with lower immunity due to illness or treatment, vaccine alone is not enough, as said patients might not develop enough immune response to vaccination to protect them against infection. This was well known and this is why some immunocompromised patients have boosters more often than every 6 months.
This doesn't mean that one shouldn't take the boosters just because they think they might not get the immune response of someone who is not immunocompromised. Quite the opposite. Every single layer of prevention counts. Boosters, wearing a mask while in crowded indoors, having rapid access to treatment such as Paxlovid, if available, in case one is infected, maybe monoclonal antibodies if they are still efficient on newer SARS-COV2 variants, etc.
sciencedirect.com/science/a...
pmc.ncbi.nlm.nih.gov/articl...
“ source is not of high trust” , Sadly I don’t believe anything that comes out of the mouths of the pharmaceutical companies either.
justice.gov/archives/opa/pr...
(Just look up fines and pharmaceutical companies.)
Neither do editors of top medical journals. azquotes.com/author/49463-M...
others editors of medical journals have also written books revealing corruption too.
I think we will have to agree to disagree on this topic. We all have our own experiences with this . I think it’s good to hear both sides so folks have a broader understanding and can then make up their own mind, which ever way they feel inclined.
You replied exactly like someone who denies science would. You touched almost every single major topic of science denialism. And reached towards conspiracy theories to support your arguments.
This is an unethical tactic you are employing on a support group for chronic blood cancers that need to be informed by science, not by your own opinions and distrust in science.
The books of a miffed editor of a medical journal dismissed for unethical behaviour is not the best example on which to base your doubts of science. There are many grifters who discovered that spreading disinformation pays more than actually doing tedious science.
Science is looking for the mechanisms behind your illness, science is the one finding treatment for your illness. Including what you call in a conspiracy theory way "big pharma."
Science is not perfect, but it has its mechanisms of accountability and ethics, it has peer review, it has corrections and retractions. Most countries have decent mechanisms for ensuring safety of medicines and accountability. They are not perfect, but there are regulations. Medical trials, reproducible results, reviews, metaanalyses, peer-review, medical committees, national bodies that regulate pharmaceutical companies, etc., all are control mechanisms. Even you acknowledge that there are fines for such deviant behaviours. Fines that do not exist for alternative health industry that is poorly regulated, unlike the strictly regulated "big pharma," resulting in alternative health industry pushing a lot of dangerous nonsense that gets people in serious health issues.
Without science, you wouldn't have a diagnosis and a treatment for a good part of MPNs.
Pseudoscience just profits from people's anxieties and credulity and delivers only snake oil and distrust in modern science.
Science denialism is disinformation.
These are tactics of science denialism, and you are using them:
academic.oup.com/eurpub/art...
skepticalscience.com/histor...
Wow TTA. We need more of this. I cannot stand anti-vaxxers who use the tried and tested methods of sowing the seeds of doubt in people minds. Really, what do they get out of it? And on a forum of 'vulnerable' patients. I've had 9 covid shots, 5 flu shots, and 2 pneumococcal. Missed my pneumoccal vax last September and just been in hospital 3 times in the last 2 weeks with a very nasty pneumonia. Only a personal story but there is so much disinformation out there, it's killing people.
A lot of interesting posts here. I can only add I'm 78, PV for 5 years, jak2 positive, taking HU. I'm pretty careful about my health but do not overmedicate. However, I've gotten every covid shot since they became available and get a covid booster every 4 months. Only contracted covid once and it wasn't too bad. Worst reaction to the covid shot/booster for me is a sore arm or feeling under the weather for a day. Your call but the risk/reward certainly favors getting the shot imho.
It's my understanding that the only vaccines we should avoid are live vaccines. The mrna based vaccines are different.
Good luck with your decision.
Dear Milokay - I am sure you did not think your post would cause such an event. You have almost been forgotten about in the correspondence.
I completely understand your feelings on this. I suffer from ET and take hydroxyurea which is holding my bloods very well. I am not a pro- or anti-vaxxer but I developed neuropathy in my feet and ankles after my first covid vaccination. Each successive booster caused worsening in my condition and eventually my MPN specialist (a world-renowned Professor) looked me in the eye and said "think very carefully before having any more boosters". Even she could not say the thing outright as then she would be classed as an antivaxxer.
I have not taken any more boosters but I am left with very painful neuropathy in my feet and ankles and I am lucky to get 3 - 4 hours sleep at night. My daughter developed asthma after taking the vaccine and my son - a strong 40-year old developed severe back pain with sciatica and was off work for six months after the vaccine. Quite a number of friends have had adverse effects. Many others suffered nothing at all.
However, I am not telling you this to alarm you but to put forward the point that the only way one can decide is to be well informed and even then it is a difficult decision. Like you I feel that my first injection hurried on the start of symptoms from my MPN.
I know very many people have benefitted from the vaccine but all those who have died or have been left with medical problems cannot be forgotten no matter how much people like to sweep these details under the carpet.
I wish you well in whatever you decide and I am also saying this post is addressed to you and I shall not be reading responses from others. Best Wishes
Dear Milokay,
I agree with Jelbea about not expecting the reaction your post received:/
I have been diagnosed with ET Jak 2+ in 2018 at the age of 59 following a mild heart attack.
I have always been careful about vaccinations. My husband would get the flu vaccine each year and I wouldn’t and often times he would get the flu and I wouldn’t and vice versa:/ It is a personal decision one makes. As a matter of fact, I recently took the Pneumonia vaccine because of my age (66) and research I did.
Concerning, the COVID vaccine neither of us were convinced there was enough testing so neither got any vaccine. My former GP was very concerned because I was considered immunocompromised.
My husband and several family members got COVID Dec. 2020 -Jan 2021. When we went through the drive in testing site and his swab came back positive, I asked them to test me and I was negative. The nurse proceeded to ask my blood type and when I told her she shook her head “No” because it was not the blood type they have found was protective against COVID.
I have not had the vaccine nor have I had COVID in these 5 years:/ I have been exposed and have taken care of my family members with COVID, on several occasions, of course, gloved and masked
My GP even did the anti body test to see if perhaps I had an immunity but came back negative.
Now, on the other spectrum, my son, sister and brother in law are all experiencing medical issues that the doctors are speculating may be caused by the COVID vaccine.
I say all this to say, it is a personal decision and at the end of the day only you will know the peace from the decision you make.
Blessings,
Mbr8076
I remembered saving these studies and research summaries below, regarding when does one acquire a driver mutation that causes a MPN.
It looks like these mutations that cause MPNs (even those that are non-canonic) are acquired decades before one has elevated blood counts. Some of these mutations are acquired in utero, before one is even born.
I hope these studies will be helpful.
"The mean latency between JAK2V617F acquisition and clinical presentation was 34 years (range 20-54 years). Subsequent driver mutation acquisition, including for JAK2V617F, was separated by decades. Disease latency following acquisition of JAK2V617F as a second driver event was still 12-27 years. DNMT3A mutations, commonly associated with age-related clonal hematopoiesis (CH), occurred as the first driver event, subsequent to mutated-JAK2, and as independent clones representing CH in MPN patients. DNMT3A mutations were also first acquired in utero or childhood, at the earliest 1.2 weeks post conception, and the latest 7.9 weeks of gestation to 7.8 years across 4 patients."
"We modelled the rates of clonal expansion and found that they varied substantially, both across patients and within individuals. In one patient, an in utero acquired DNMT3A-mutated clone expanded slowly at <10%/year, taking 30 years to reach a clonal fraction of 1%, whilst a clone with mutated-JAK2, -DNMT3A and -TET2 expanded at >200%/year, doubling in size every 7 months. JAK2V617F as a single driver mutation also expanded variably across patients, highlighting that other factors, which may include germline, cytokine or stem cell differences between individuals, also influence selection for driver mutations. JAK2V617F associated clonal expansion rates in MPN were greater than that reported for JAK2-CH. Furthermore, rates of expansion in the cohort predicted time to clinical presentation, more so than age of mutation acquisition or tumour burden at diagnosis. This suggests that JAK2-mutant clonal expansion rates determine both if and when clinical manifestations occur.
Driver mutations and rates of clonal expansion would have been detectable in blood one to four decades before clinical presentation.
MPN originate from driver mutation acquisition very early in life, even before birth, with life-long clonal expansion and evolution, establishing a new paradigm for blood cancer development. Early detection of mutant-JAK2 together with determination of clonal expansion rates could provide opportunities for early interventions aimed at minimising thrombotic risk and targeting the mutant clone in at risk individuals."
ashpublications.org/blood/a...
The study above points out that the mutation would be detectable in blood 10 to 40 years before clinical presentation, which means before one has elevated blood counts, in the case of ET and PV.
Another study on this topic:
pmc.ncbi.nlm.nih.gov/articl...
This one is also informative:
"Here the scientists trace back the disease progression of MPN in individual patients to the initial mutation within a HSC. Strikingly, they find that the mutation occurs decades before diagnosis, at approximately age 9 in a 34 year-old patient, and approximately age 19 in a 63 year-old patient. These findings have implications for both improved MPN diagnosis and potential new treatments using specific inhibitors for the mutation."
Covid
Advise on timing of covid jab and Pegasys injection 
Covid booster jab done
