I've been feeling off for the last few months and have had a number of blood tests - the 1st I was told my vit D was really low and started supplements, then I found I was iron deficient and started iron tablets. However, I've been feeling worse and worse - very tired, off balance, dizzy when standing, muscle cramps and weakness, poor digestion and constant headaches. So a doctor suggested I had my b12 checked and it came back as 50, which I'm told is quite low? However, the doc said its common to have false b12 results and so requested it to be tested again along with an autoimmune profiling. The second b12 test has come back at a level of 49 and I have tested positive for parietal cell antibodies. However, after all of this my doc said he's still loathed to say it's PA as my blood count has come back normal (this time - first time my red blood cell count came back slightly high).
I'm so fed up of feeling rubbish! Has anyone suffered anything similar? Any ideas of what else could be causing these issues if not PA?
Thanks x
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Amylou2828
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I've just checked - normal is anything from 180-1000. To be considered low you have to have levels below 145... So I'm pretty low by the sounds of things!
While it is technically possible that you have something other than classic autoimmune PA, your levels are so low and the positive parietal cell antibody test mean that you really should be getting injections of B12, because not only do you have a clear deficiency, you also have an autoimmune response that is destroying the parietal cells that line the stomach. It is parietal cells that make instrinic factor which is needed to be able to absorb any B12 taken orally.
Your doctor may be loathe to label your deficiency, but how are they *treating the problem*? You can be deficient and show symptoms without actually being anemic. Many doctors seem to be unaware of that fact, so perhaps yours is under a false impression. You may need to bring your doctor more information or otherwise prompt them to educate themselves on the topic. You should insist on correct treatment though. Your doctor would not be able to argue the fact that parietal cell antibodies affect absorption, therefore oral supplements will be worthless as a treatment.
You may have a battle ahead of you. Some doctors are just stubborn and will refuse treatment. If that happens, I suggest finding a better doctor.
Well the most I got from him this afternoon was that he'll ring haematology tomorrow to discuss my options and that if we're "clutching at straws" it could be because I'm on the contraceptive pill?!
I'm going to wait and see what is said tomorrow, but my family have private health insurance, so I think it might be a good idea to ask to be referred to a specialist..?
A referral is a good idea. There are a couple of directions you could go at this point for what type of specialist to see. You could either ask to see a gastroenterologist about the multiple vitamin deficiencies your tests have turned up. That would likely have them looking into things like celiac or ulcerative colitis as possible causes. Or you could ask to see a hematologist, which would likely result in you being told you're not anemic so there's no need to see a hematologist (I'm a bit jaded about hematologists due to a couple of bad experiences). Or you could ask to see a neurologist for the balance problems. Unfortunately there is no guarantee that any type of specialist will be any more knowledgeable about B12 deficiency than your current doctor or that they will agree to treat your deficiency. There is no specialty that is PA specific. After seeing one regular GP, two hematologists, two gastroenterologists, and one neurologist, I've actually had better results from seeing a naturopath. Hopefully you'll have better luck than I did.
You have very low B12 and you're positive for anti-GPC (Gastric Parietal Cell) antibodies. Now, neither is sure-fire proof of PA on its own (about 20% of anti-GPC positives are due to other causes). But the two of thewm together is a very, very good indication of PA.
The idea that one needs to show signs of macrocytic (large cell) anaemia is an old one. For a start, iron-deficient anaemia leads to small red cells. Pernicious anaemia can cause large red cells. Guess what happens if you have both, one making cells tend to be larger, t'other making them tend to be smaller? That's right, the cells are normal sized (see, you've just proved yourself more intelligent than your doctor).
But, even without iron-deficient anaemia, you can have PA without macrocytic anaemia. Here's what the British Committee on Standards in Haematology (the biggest brains in blood medicine in the country) says in their guidelines - bcshguidelines.com/document...
"In patients with classical megaloblastic anaemia, the presence of a low serum cobalamin level and objective assessment of response in terms of the rise in haemoglobin concentration clearly outlines the treatment pathway. However, the majority of patients do not have such a clear cut picture. Neurological presentation (peripheral neuropathy. sub-acute combined degeneration of the cord) may occur in the absence of haematological changes, and early treatment is essential to avoid permanent neurological disability. Low cobalamin levels of uncertain significance may occur with non-specific symptoms and no anaemia"
and
"The absence of a raised MCV (Mean Cell Volume - a sign of big cells) cannot be used to exclude the need for cobalamin testing
since neurological impairement occurs with a normal MCV in 25% of
cases."
It's very, very likely that you have PA and you need to be started on a course of injections - 1000ug every other day for two weeks, then every three months. If not, as stated above, you're at risk of permanent neurological disability.
Are you in the UK? I've assumed you are so apologies if some of this is not relevant.
The reference range you give is the same as in my area of the UK. I'm a bit shocked that the GP is reluctant to consider PA and that they have not considered giving you a trail of B12 injections. Some medics do not realise that PA can be found in people of all ages. The PAS (Pernicious anameia society) has members aged from about 2 years to 80 plus years. Your B12 is very low. If B12 deficiency is not treated adequately then it can cause permanent neurological damage and if left untreated, it could be fatal.
I'd urge you to contact the PAS (Pernicious anaemia Society).
Office open between 8am and 2pm every day except Sundays
Blood Tests
There are other blood tests that may help to establish whether or not a patient has B12 deficiency. see link. A blood smear aka blood film can also be useful. B12 deficiency can cause changes in the shape of some blood cells.
People with neurological symptoms and B12 deficiency should be treated more intensively according to the BNF (British national formulary) . If you are in the UK, your GP will have access to the BNF. He/she will probably have a copy on their bookshelf. The info your GP needs is in BNF Chapter 9 Section 1.2
I'd recommend you reading the following documents. I gave copies of all these to my GPs.
1
"BCSH Cobalamin and Folate guidelines"
Recent document. I was told NHS should be following these guidelines. There is guidance on treatment and diagnosis. I found page 29 very useful, a diagnosis flowchart. Cobalamin is the scientific name for B12
Useful summary, contains this statement which might be of interest to your GP.
"If the clinical features suggest deficiency then it is important to treat patients to avoid neurological impairment even if there may be discordance between the results and clinical features"
Useful links below. Some may be of interest even if you're not UK based.
"However, after all of this my doc said he's still loathed to say it's PA as my blood count has come back normal (this time - first time my red blood cell count came back slightly high)."
I learnt from experience to always get copies of my blood tests especially folate, ferritin, B12 and full blood count (FBC) , as what I was told face to face or over the phone was not always what was on the copy. It can help to track results over a period of months/years in my opinion.
"then I found I was iron deficient and started iron tablets"
"had my b12 checked and it came back as 50, which I'm told is quite low"
Do you know your MCV and MCH results? these would be on a FBC (Full Blood Count) aka Complete Blood Count in USA. High MCV and high MCH can indicate the possibility of macrocytosis. Macrocytosis (enlarged red blood cells) can occur in people with B12 deficiency. Some people with PA/B12 Defic do not get macrocytosis.
Low iron can make red blood cells smaller. Low B12 and/or low folate can make red blood cells larger. If a patient has both conditions their red blood cells can appear normal size and a GP might miss problems. Macrocytosis due to low B12 and/or low folate can be masked if the patient also has low iron.
Wow, thanks for such a detailed reply! I am in the uk.
I was tested for coeliacs and thyroid issues a few years ago as I was feeling tired, suffering from hair loss and IBS type symptoms, and both my mum and brother have Graves' disease, but both came back fine. In fact, I think that was the first time I found I had iron deficiency anaemia (I've had it 3 times now).
I haven't seen a copy of any of my results, only know what I've been told by my doctor. Think I'm going to request a copy!
Really sorry that your GP is so unaware of what B12 deficiency is. I would seriously consider changing your GP. At the very least you need to draw their attention to the BCSH guidelines which acknowledge that anaemia isn't always present in B12 deficiency but if neurological problems have already developed it is important not to delay treatment as failing to treat the neurological problems can result in permanent nerve damage
see summary on page 2... and also details on page 8 about treatment regimes.
PA, an autoimmune response which destroys the mechanism that the body uses to absorb most of its B12. As a result it is one possible cause of a B12 deficiency. There are others but as you have antibodies that would indicate that for you it is PA that is causing your deficiency.
It is the B12 deficiency that the autoimmune response causes the symptoms you refer to. B12 is used to maintain a lot of the bodies systems including cell reproduction, maintaining the insulating layer around nerve cells, reprocessing waste products such as homocysteine and MMA into the starting components used by other key processes.
Anaemia develops because B12 isn't available for healthy cell reproduction. The most common form is macrocytosis.
The nerve problems you have are caused by the effects on the nervous system.
Although blood problems are the first to materialise in the majority of cases, nervous disorders do manifest themselves first in a considerable numbers of cases.
Further, if folate levels are high this can counteract and mask the anaemic affects of B12.
So, to summarise: you have the symptoms of a B12 deficiency. It is B12 deficiency that causes these symptoms NOT anaemia. The symptoms you have need to be treated urgently. The fact that you don't seem to have anaemia is not relevant.
However, a lot of the guidance available to GPs (including NICE guidelines) is pretty confused and on one level it is easy to understand why at a cursory glance they get confused and think that it is all about anaemia. The NICE guidelines are found under anaemia with no cross reference under neurological problems and the focus is on blood work, using tests that are known to be flawed - though the readings you report are clear evidence of an undeniable deficiency which - and I don't think this can be emphasised enough- needs to be treated as a matter of urgency.
See this alert re problems with the B12 serum test - though this clearly relates to results coming back in the normal range not being indicative that someone is not deficient - somewhat different from the impression your GP seems to be giving in dithering on results that are clearly too low.
There are also problems with the tests for PA (IFA and PCA) and these tests are 50% accurate at best, thgouh generally it would be accepted that if you get a positive that means you do have PA, rather than the other way round. So, possible that your GP is getting confused with these tests.
I have also not tested positive for PA but need a lot of B12 and supporting supplements to be well. You can be seriously B12d (deficient) without having PA: it often is harder to get Drs to treat you but is just as essential.
Good luck! I hope you can get the treatment you need and start to feel better soon.
Forgot to mention these books which I found very useful. I gave a copy of Martyn Hooper's book to my GP. Martyn Hooper is the chair of the PAS. There are a couple of local PAS groups in the UK. It is not expensive to join. Martyn has written several books about B12 deficiency and PA.
"Could It Be b12" by Sally Pacholok and JJ. Stuart
When I read this it was a lightbulb moment. Parts of it were like reading about myself.
"What You Should Know About Pernicious Anaemia and Vitamin B12 Deficiency" by Martyn Hooper
Some of the case histories in his other books made me cry because again it was like reading about myself.
Sometimes it is difficult to get a diagnosis of B12 deficiency. I have been ill for over 10 years and highly symptomatic for B12 deficiency all this time but with most of my results normal range and I was negative for IFA tests.
Has your GP given you an IFA test? (Intrinsic Factor antibody)
Be warned that the IFA test is not always reliable. It is still possible to have PA with a negative result. The BCSH Cobalamin and Folate Guidelines mention Antibody negative PA. Page 29 of teh BCSH Cobalamin Guidelines indicates when testing for IFA is recommended.
I am surprised by the difficulties you are having as you have some evidence eg "positive for parietal cell antibodies"
B12 deficiency can be insidious, it can happen very slowly and gradually. Sometimes the changes in physical and mental health are put down to aging or the menopause or misdiagnosed as another condition.
It is worth fighting to get a diagnosis because the consequences of untreated B12 deficiency can be very severe. I was forced to treat myself because I could not get treatment from NHS. I believe many years without treatment have left me with some permanent damage.
Useful link if unhappy about treatment. ideas for writing to GP.
"I was tested for coeliacs and thyroid issues a few years ago as I was feeling tired, suffering from hair loss and IBS type symptoms, and both my mum and brother have Graves' disease, but both came back fine.2
Just to mention that if Coeliac symptoms continue after a negative test result then my understanding is that GPs need to do other tests. Have you ever had an IgA test?
Details of further tests for Coeliac disease here.
I had IBS symptoms for years which continued after a negative Coeliac test result. At the time I was unaware that the GP could have tested IgA and done other types of Coeliac test. I later gave up eating gluten and the IBS symptoms stopped. I still wonder whether or not perhaps i am coeliac after all.
In Pernicious Anaemia your body's immune system makes antibodies that attack and destroy the gastric parietal cells (GPCs) in your stomach. These cells have two functions:
They produce hydrochloric acid. This is essential for proper digestion of foods, especially protein and for releasing B12 bound to proteins in your food.
They also produce something called Intrinsic Factor (IF). This is a protein that binds to the released B12 and carries it across the wall of the ileum (part of your small intestine).
Without the GPCs the B12 molecules stay bound to the food proteins. Any that does get released can't move from the ileum to the blood because there is no IF to carry it across.
Hi thanks fbirder. I really wanted a peer reviewed study with references to give my doctor as he is insisting I take largeoral doses of B12 instead of injections I've had in the past. He cited some info he had in one of his reference books from NICE that oral is a good as injections! I have B12 and iron anaemia but have not let my B12 go low enough ( I need to function!), to get a postive test for PA - I have been tested in the past.
"Pernicious anaemia is an autoimmune disease with atrophy of
the gastric mucosa of the body and fundus of the stomach. This
reduces the number of parietal cells that produce the intrinsic
factor necessary for absorption of vitamin B12"
and
"If the cause is irreversible then parental therapy should be continued for life."
and
"However, UK national consensus is
that there are arguments against the use of oral cobalamin in
severely deficient patients and those with malabsorption."
As your doc seems so keen on NICE, perhaps they should read the latest (July 2015) guidelines - cks.nice.org.uk/anaemia-b12...
"•How should I treat a person with vitamin B12 deficiency anaemia?
For people with neurological involvement:
oSeek urgent specialist advice from a haematologist.
oIdeally, management should be guided by a specialist, but if specialist advice is not immediately available, consider the following:
Initially administer hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement, then administer hydroxocobalamin 1 mg intramuscularly every 2 months.
For people with no neurological involvement:
oInitially administer hydroxocobalamin 1 mg intramuscularly on alternate days for 2 weeks.
oMaintenance dose (where the vitamin B12 deficiency is not thought to be diet related): administer hydroxocobalamin 1 mg intramuscularly every 3 months for life (standard dose)."
"I really wanted a peer reviewed study with references to give my doctor as he is insisting I take largeoral doses of B12 instead of injections I've had in the past. "
Hi, Auldreekie
Have you contacted Martyn Hooper at the PAS? He has helped people before who have had their treatment changed from injections to oral tablets. If you leave a message the PAS will get back to you within a few days. You do not have to be a member to ring them.
This blog entry mentions when Gps have tried to change injections to oral tablets.
Two books I found helpful
Could It Be b12 by Sally Pacholok and JJ, Stuart
"What You Should Know About Pernicious Anaemia and Vitamin B12 Deficiency" by Martyn Hooper
This book is very recent (Oct 15) and contains up to date info. I gave a copy to my GP.
Do you have neurological symptoms? My understanding is that the treatment is currently injections for life according to the BNF (British National Formulary) Chapter 9 Section 1.2. all Gps have access to the BNF.
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Any Advice on PA & B12 plus iron & ferritin 
Am I just just b12 deficient or PA? So confused what to do next :(
B12 treated but anemia no better
What tests should be administered on a regular basis and how frequently for PA and/or B12 deficient patients?
PA / Low iron early stages with NHS - advice please 
