Hi, everyone! I'm hoping those of you who have more experience appraising lab results can help me here, since I still have two weeks before I can go to the hematologist to have these explained to me. I have iron deficiency anemia (formally diagnosed) and, until recently (?), what I assumed to be pernicious anemia, given the following baseline results:
Intrinsic Factor AB - reactive / positive
B12 - 248 pg/ml (ref. range 180-914)
Ferritin - 8 ng/ml (ref. range 11.0-306)
MMA - 321 (higher than normal reference range of 87-318)
After two iron infusions and two shots of B12, which were both prescribed to me, these are my results, which largely seem to be normal:
Intrinsic Factor AB - listed as "normal" (0.9 AU/ml in a reference range of 0.0-1.1)
B12 - 203 (lower)
Ferritin - 667 (!!!!! - muuuuch higher)
MMA - 175 (normal)
So, my questions are:
1) why is my B12 dropping even with the shots?
2) I've read here (thank you for your knowledge) that the IFAB test can yield false negatives some of the time. But my second, more detailed test shows antibodies, albeit in a normal range. Is this a thing? And, as a result, is my doctor likely to say that I don't have PA?
3) did the successful iron treatment bring down my MMA levels? Is MMA primarily a concern of PA or IDA (or both)? and, finally,
4) to what extent can I expect to be driven crazy by a ferritin level of 667, considering that iron levels that are too high can be just as dangerous as levels that are too low?
Thanks so much for your time and consideration!
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It is my understanding that an IFab positive is 95% accurate - so there would be little point in a second test once a positive result has been returned.
An MMA (methylmalonic acid) test is a good second test after serum B12 has been tested. It is quite specific to B12 deficiency - since B12 joins with MMA, if there is a shortage of B12 available, MMA begins to build up in the blood. The test should be done early, as obviously once B12 injections are introduced, MMA levels should drop to normal fairly quickly. Certainly by the time the loading set of injections are done. Very high MMA levels can be seen in B12 deficiency before treatment- although not often done at this stage. Yours would have been considered mildly raised.
Two elimination tests: Renal problems should be ruled out by blood test as this can raise MMA, and SIBO (small intestine bacterial overgrowth) can cause B12 deficiency as well as other vitamin deficiencies as the bacteria can rob them from you - this can be ruled out after, if MMA found to be raised (by fasting hydrogen breath test) - and treated with antibiotics, although it can return.
Raised MMA continuing after injections have started can indicate a functional B12 problem at cell level. It took 3 years (and a lot of B12!) for my MMA level to finally drop into range.
Your B12 was in range but lowish, and I'm wondering what time has elapsed since 2x B12 injections given ? Usual for B12 to be very high after an injection.
I have no idea why your ferritin went from 8 to 667 - from ridiculously low to extremely high - and wonder if they measured your ferritin between the two infusions. I've never had an iron infusion, so unaware of what a good result would look like.
As you can see, I'm not a scientist. I hope this can help you to investigate a few more leads, and hope you get some answers to clarify things. Certainly some atypical results there, but I'd cling on to your IFab positive result if I were you. Ask for a printout if you don't have one already.
Thanks so much for this clear and useful response! (I’d never know that you’re not a scientist )
Both of the B12 shots have been about a month apart — my last was Sept. 12, with these labs run on Oct. 1 (so, about three weeks apart). I didn’t receive loading doses.
Would I need the renal or SIBO tests if I’m positive for the IFAB? (Wondering how much PA is independent from — or a result of — those two other phenomena.)
It seems like my MMA levels have become better despite the fact that my B12 is lower — so does that mean we can attribute the drop in B12 to its being effectively used in binding with the MMA?
They didn’t measure anything between the two infusions; I think these labs are supposed to serve as our check-in.
No need to respond here — I’m sure you’re busy, you’ve already gone above and beyond, and I’m mostly just thinking aloud — but thank you so much for the information above!
Sorry to interrupt, but I don't think you're not positive for IFAb. It's negative. I wish they wouldn't report 'AU' and a range, as it's confusing.
Your ferritin has increased due to the iron therapy. You don't state what's happening to your MCV, MCH and RDW, but in response to iron, it would be reasonable to expect them to increase, and then the RDW should resolve in a few weeks. The serum B12 level is still normal, but as your body regenerates, making more decent quality red cells, it'll consume some B12, folate and a whole host of other things. It's in a state of flux. It should settle down soon!
Thanks for your response! Just so I understand — you’re saying that I can have a certain level of IFAB (“reactive,” as on the first test, and the “normal” level of 0.9 AU/ml on the second) but not PA? Is it possible that, because it’s less detailed, the first test is essentially saying the same thing as the second — that there are IFAB present, but not at critical levels?
And does it matter that I had no B12 shots or supplementation before the first test but had commenced treatment before the second?
Yes, my other blood levels (MCV, MCH, etc.) have all fortunately returned to normal levels now that my iron has been restored (whew!). Good to know that the lower B12 is a result of my body repairing itself (yay!).
Hi. thanks for the followup. The fact that you've got some 'noise' from the assay may be just that. It could be non-specific. If the 0.9 AU value means anything then, given time, it will probably rise. I was more used to seeing 'positives' at much higher levels. So, just because you have a low level of something, it may not be IFAb. It may well be a non-specific effect, a cross-reaction. Sample noise. Don't panic.
Cherylclaire - MMA isn't specific to B12 - there are a number of things that can cause raised MMA and these can't really be ruled out without looking at other metabolites that indicate eg kidney function. The fact that it went down after treatment with B12 does suggest that B12 was the reason why it was raised in the first place
Sorry - when I said "quite", I meant as opposed to "highly".
If renal problems and SIBO ruled out, is there anything else that can raise MMA ?
Yes - it seems that the MMA was just waiting for more B12 - this would not rule out SIBO as the cause of low B12, but the IFab positive would be pointing strongly to PA.
The above would imply that the natural mechanisms for removing excess B12 from your blood (mainly filtering out by the kidneys and excretion in urine works faster than in most people - people vary a lot - so you are likely to need B12 shots more frequently than the average.
MMA dropping implies that your cells had enough B12 to deal with the build up (assuming you didn't also have a kidney problem which has been dealt with).
To my knowledge iron doesn't have an effect on MMA - B12 does but ask your haemo when you see them.
The ferritin result will be down to the iron infusion - its one measure of iron status but it is not the only one and you really need to talk with your haemo about interpreting the result but at this stage I wouldn't worry about it - ferritin is a protein that binds to iron so its only an indirect measure and I suspect that an iron infusion probably makes it a meaningless measure but again - speak to your haemo.
The first IFA result is a positive which is strong evidence that you have PA as the cause of the B12 absorption ... and that probably contributed to the iron deficiency. The second IFA test has come back negative but as the test isn't very sensitive (gets confused over whether it is picking up IFAB or other metabolites) it has a range that doesn't start at 0 and also has a strong possibility of false negatives - to be honest repeating the test after the initial positive was a waste of money as the negative doesn't rule out PA.
Yes, I wish they hadn’t had to repeat the IFAB test, as I know how confusing it can be for doctors to have two different results to contend with — my GP was supposed to forward my baseline labs to the hematologist, but somehow that didn’t happen before my appointment, so the whole thing was largely a waste of time and they ended up running all of the tests again (sigh).
Do you know if the PAS has any resources I can share with a hematologist who I fear might be more convinced by the second test, since it’s more detailed (especially if — yikes — it turns out that I need more B12 than most)?
this covers the various diagnosic tests and how flaky IFAB is - even referring to IFAB negative PA where another cause can't be identified and IFAB test has come back negative.
There is a helpline number that PAS members can ring.
Lots of B12 info in my replies on the the thread below eg symptoms, causes of B12 deficiency, B12 books, B12 websites, B12 articles/documents and a few hints about dealing with unhelpful GPs.
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