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Songbird1 profile image
13 Replies

will pernicious anemia show in a blood test if you are having b12 loading dose injections ?

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Gambit62 profile image
Gambit62Administrator

The test for PA (IF antibodies) is generally affected by the very high serum B12 levels just after an injection - the effect is to signficantly increase the risk of false positives (ie results saying you have PA when you don't). So, if you are having loading doses when you do a test a positive may not mean that you do actually have PA

In other circumstances (which would be covered by leaving it 2 weeks after an injection - though this may be as little as 24 hours for some test methods) the risk of false positives is very low.

However, as the test is notoriously prone to false negatives - about 50% of the time - a negative doesn't rule out PA.

Retteacher profile image
Retteacher

According to the Consultant Haemotologist who spoke to the recent PA Conference, the B12 serum and MMA tests will not give reliable/accurate results unless supplements are stopped for 6 months. Others believe at least 3 months.

fbirder profile image
fbirder in reply toRetteacher

They will give accurate results for serum B12, but those results will be high. You need to wait many months for a serum B12 test to accurately diagnose a B12 deficiency.

An MMA test may show abnormally high levels soon after injecting if there is a functional deficiency present (lots of B12 in the blood, not enough in the cells).

Nackapan profile image
Nackapan in reply tofbirder

So if the MMa has high levels you need to have more frequent injections?

I've never had a MMA or homocysteine test . I wonder if I should?

One also never had a intrinsic factor done

Before my loading injections started I had the parietal cell antibody test which was negative.

I know have learnt its hardly used now.

My Gp is usually very good Iif i ask for anything reasonable .i seem ti be going in circles trying to improve

Perhaps a MMA test would be helpful?

Retteacher profile image
Retteacher in reply toNackapan

The sensitivity of the MMA test has not been fully determined. It appears to be quite weak. Neither test correlates well with patients symptoms. A high value for MMA indicates that B12 is not getting into the cells BUT it returns to a normal level with very small doses of B12 in patients who have had bariatric (stomach) surgery. Needless to say the dose is insufficient to stop the patients having symptoms. Another possible problem with patients who have a 'functional' deficiency is that B12 may not be getting into the central nervous system whilst being sufficient in the general circulation to keep the MMA marker low. This is a hypothesis put forward by US researchers who believe that this can happen in patients over 55 years of age. Considering that the standard B12 serum test has a false negative rate of about 45% and the free B12 test is not much better, this is why the guidelines have a pragmatic approach to starting injections if neurological damage is suspected. Neuropsychiatrists in particular set their B12 serum level cut-off for abnormality very high. There is no gold standard test that will pick up all patients that have a B12 problem, hence a significant group of patients who produce results within the normal ranges but still respond to B12 injections as reported in the Mayo Clinic Proceedings last year. When patients are suffering and there are reasons to suspect B12 deficiency, clinicians have to use their clinical judgement. Many are insufficiently experienced and are used to implicitly accepting laboratory test results without realising how flawed/insufficiently sensitive these particular tests are. It is very unsatisfactory to have to rely on a 'therapeutic trial' of injections in some patients, as there is no proven or tested tool for objectively measuring improvements in what are a host of symptoms that are non-specific for what causes them. Nevertheless, if other metabolic disturbances and other conditions have been excluded, we patients desperately need help and appreciate those clinicians such as Dr Chandy that try to help.

fbirder profile image
fbirder in reply toRetteacher

"Considering that the standard B12 serum test has a false negative rate of about 45%"

You'll have to explain what you mean by 'false negative' when it comes to the serum B12 test.

Retteacher profile image
Retteacher in reply tofbirder

False negative in terms of failing to identify patients that have a B12 deficiency. This figure is quoted from the review of cobalamin laboratory tests published in 2017 by Dr Harrington (St Thomas 's Hospital in London).

fbirder profile image
fbirder in reply toRetteacher

So you are saying that the serum test only manages to get half of those who are deficient?

I'm not sure I'd agree that it is that many. But there's not a lot that can be done about it. Except for treating based on symptoms, not numbers on any test.

The idea that you can fix things just by setting the lower limit 'very high' is not workable. It just means that you'll get loads and loads of people being labelled as deficient when they're nowhere near it.

In Hull and East Yorkshire they set their serum test so that 4.5% of normal people fall below the bottom of the range. 9.5% of non-deficient people fall within their intermediate range. hey.nhs.uk/wp/wp-content/up...

If 10% of people are really deficient (probably an overestimate) then testing 1000 people will get 90 people below the bottom of the range (45 'non-deficient' plus 45 deficient - assuming 55% false negative). Then you will get 150 in the intermediate range (95 'non-deficient plus 55 deficient).

So, you have half of the people who test 'below normal' being not-deficient and 63% of those who test 'intermediate' being not-deficient.

Obviously, just ramping up your normal range isn't going to work. The higher you put it, the more false positives you're going to get - until almost everybody is labelled as deficient.

No, the way to do it is to look at symptoms.

I'll bet that the neuropsychiatrists don't treat everybody with B12 levels below x00. When they say they set their cut-off very high, they mean that they only rule out a B12 deficiency in somebody with symptoms of a b12 deficiency if their levels are very high.

It all comes down to symptoms. If somebody has the symptoms of a B12 deficiency and if there's no other obvious cause of those symptoms, then treat with a series of B12 injections. If they get better, then carry on doing that forever.

That is what HEY recommend in their flowcharts.

Retteacher profile image
Retteacher in reply tofbirder

Yes, I agree with your conclusions. It is down to symptoms ,but we need a tested measure of symptom relief to help quantify the benefits of injections-or at least the doctors would be happier if they had one.

The 45% false negative for the serum B12 test is horrifically high. Much of this appears to be related to the introduction of the newer 'economical assays' -reference an American study of about 220 proven PA patients whose blood samples were tested retrospectively. Compared to the older assay method, the newer tests from two suppliers failed to identify 25 to 35% of the patients

Also B12 levels decline with age so that the 'normal' and 'patient' ranges in the elderly are overlapping even more. You are right about the neuropsychiatrists only using the high cut-off (circa 550 pmol/l I think) to exclude patients above that. However, Prof D.Smiths work on brain shrinkage in the areas associated with Alzheimer's indicated that such shrinkage was prevented or slowed if serum B12 levels were maintained above circa 670 pmol/l. Hope I have quoted the units correctly.

The point is the significance of the serum measurements has to be treated with caution and too many doctors are not sufficiently aware that there is such a large grey area of overlap between normal people's values and patients with B12 associated problems.

fbirder profile image
fbirder in reply toRetteacher

Prof Smith's results were in patients with high levels of homocysteine. So he used another indicator of a B12 deficiency.

Nackapan profile image
Nackapan in reply toRetteacher

Thankyou for your reply .

So it's back teally to treating symptoms . So MMA not a conclusive indicator of b12 not reaching the cells.

Can be an indicator though perha8w only at the beginning when serum is within range but symptoms are there?

Like all of us I would love to know if the b12 injected is getting g to cell level.

When I find a regime that gives some life back i will stop searching.

Retteacher profile image
Retteacher in reply tofbirder

You may be technically correct in terms of accuracy in measuring B12 serum levels, but I meant accuracy in identifying a B12 deficiency/abnormality.

Songbird1 profile image
Songbird1 in reply toRetteacher

Thanks everyone. Had my 6th loading dose today and start folic acid. B12 was on 138 and only know folate is low. Hoping to feel better soon.

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