diagnosis

[Ronsville2]

Can anyone explain how Pernicious Anaemia is diagnosed.

[Narwhal10]

Hi Ronsville2

Here’s a link from PA society

pernicious-anaemia-society....

[Gambit62 Administrator]

Ronsville2 - there are a few things that get easily confused. PA, the B12 deficiency it causes and the anaemia caused by B12 deficiency.

PA is an autoimmune gastritis - it attacks the mechanism that your body uses to extract B12 from food - in the terminal illeum. this means that PA results in B12 deficiency - and the symptoms associated with PA are the symptoms of B12 deficiency. These include a particular type of anaemia in which red blood cells are larger and rounder than normal - macrocytosis, but this isn't necessarily one of the first symptoms to materialise.

Macrocytosis is diagnosed using a full blood count. As macrocytosis is also caused by folate deficiency, folate levels should also be checked.

B12 deficiency is usually diagnosed using a serum B12 test but the test is a bit of a blunt tool and it is only accurate to 20%. In some places they use a test called 'active B12' or Holo-T - which looks specifically at then amount of B12 in your blood that is bound to the protein that enables it to transfer into cells, The test is more accurate but is still problematic.

Both serum B12 and active B12 look at the amount of B12 in your blood, but don't provide any indication of how well this is being transferred and used in cells. They are useful for detecting an absorption problem as individuals maintain blood levels of B12 at pretty constant rates using stores in the liver. If you have an absorption problem such as PA then that affects the release of B12 stores as well and over time B12 levels drop - so a downward trend or a significant drop in blood levels of B12 over time is a pretty good indicator of a B12 absorption problem.

There are a couple of clarifying tests for B12 deficiency that look at bi-products that build up if your cells don't have enough B12 to break them down. - Homocysteine and MMA. These do provide a measure of what is happening in cells and if the cells are getting the B12 they need. However, they can be raised by other things - eg folate deficiency in the case of homocysteine and Liver/kidney problems in the case of MMA - so they need to be run in a context that rules these possibilities out.

There are a number of things that can cause B12 absorption problems - including other disorders affecting the gut like crohn's and sometimes coeliacs, use of PPIs to reduce stomach acidity (something needed to enable the absorption of B12 in the gut), some other drugs - Metformin used to treat diabetes and a few other conditions, H pylori infection, SIBO (another infection). Generally it is easier to rule these causes out than it is to start with trying to confirm a diagnosis of PA.

There used to be a test which was very good for determining absorption problems - the Schilling test - but the test isn't available any more. The main test that we are currently left with are test looking for antibodies produced by the autoimmune gastritis - but the tests are not that accurate - GPC (gastric parietal cell antibodies) gives false positives quite regularly and IFA (Intrinsic Factor antibodies) gives false negatives 40-60% of the time - meaning that a negative is a long way from ruling out PA. The guidelines used in the UK refer to IFAB-negative PA as a result. If you can't identify the cause the assumption at the moment is that it is PA.

There is some work done on using gastrine - a hormone that regulates the production of gastric acids - that seems to be continually high in patients with PA - though I'm not sure how well this is recognised as a diagnostic test.

[fbirder in reply to Gambit62]

"There is some work done on using gastrin - a hormone that regulates the production of gastric acids - that seems to be continually high in patients with PA - though I'm not sure how well this is recognised as a diagnostic test."

I don't know why it's not used more.

There are two main reasons why a person might have very high levels of gastrin (not just slightly raised).

The first is a gastrin-secreting tumour, called a Type 2 gastric NET. They are often caused by a genetic mutation in a gene called MEN1. If your high gastrin is caused by one of these tumours then you want further investigation in case the cancer spreads.

The other main cause of high gastrin is a lack of stomach acid. That can be caused by getting older, taking PPIs for a long time or PA. The first two are easy to rule out. Hypergastrinaemia in common with low B12 should be a good indicator of PA.

[fbirder]

Pernicious Anaemia is an autoimmune disease. Your immune system attacks the body's equipment for making a protein, called Intrinsic Factor, needed to absorb B12. Without IF your body cannot absorb any B12. One test for PA is to look for antibodies that directly attack IF. If you test positive then you, almost certainly, have PA. But half of all those with PA test negative.

The other way (how I got my diagnosis) is to look for the underlying cause of PA - Autoimmune Metaplastic Gastric Atrophy. During a gastroscopy they noticed I had gastritis (the GA of AMGA) and that it was restricted to two of the three areas of the stomach (the fundus and corpus, H. pylori infection also causes gastritis in the antrum). Biopsies also showed metaplasia (the wrong type of cells for that place and the M of AMGA). Finally a test showed positive for antibodies to gastric parietal cells that make IF (the A of AMGA). Combine that with B12 so low it could not be measured and that is definitely PA.

The final way of diagnosing PA. The easiest and most underused way. Is by exclusion. If the patient has a B12 deficiency, it isn't dietary and there are no other causes (gastric or ileal surgery, use of PPIs or metformin, abuse of nitrous oxide, infection with a fish tapeworm or other gut parasite, Crohn's disease, coeliacs disease) then, by default, PA is, by far, the most likely cause.

[Ronsville2]

Thanks to all for the very valuable information. Developed strange shooting/buzzing pains in legs, so going for a private nerve/muscle induction test tomorrow, as treatment from the GP's has been ghastly. There seems to be very little GP knowledge about this condition. Quite frightening really !