Can someone explain why my husband's serum levels of B12 levels are always normal, his IF is equivocal, his hematologist decided he has PA.

[dll5602]

All the other docs say "they don't buy it" as a reason for his symptoms and that he shouldn't need B12 injections but it's the only thing that helps him.

[Hidden]

Bravo to the Haemotologist. The only foolproof way of diagnosing B12d is by gauging a patients response to treatment. There are no gold standard tests. In terms of your husband the salient points are:

- The serum B12 test is unreliable. You can be deficient at any level. This could be because your active B12 is low (most of the B12 in your blood is inactive haptocorrin rather that active holotranscobalamin). Or because the test assay itself is unreliable (there is a UKNEQAS warning about flaws in the test). Or because you may have a lot of B12 in your blood, but lack the means to transport it to the cells where it's needed. This could be due to genetic transport defects or inborn errors of metabolism, or genetic defects affecting methylation.

- The intrinsic factor antibody test misses 50% of sufferers. It is a highly specific test, if you test positive then you definitely have PA, it is diagnostic. However if you test negative it means absolutely nothing one way or the other. You could still have PA, or not.

So if your husband responds to treatment and has a supportive Haemotologist then all I can say is hang on to this doc, and thank your lucky stars, because most people would be left to suffer.

You can read lots more about B12d on this link:

b12deficiency.info

H x

[dll5602 in reply to Hidden]

Yes, bravo to the hematologist; although, it was with reluctance that he started him on B12 shots. The pharmacy is the one who got him to increase the frequency because I was in so often refilling his prescription. He made a comment that it doesn't make sense that he needs it because it should circulate in his system for months. I was the one pushing, because anecdotally, I knew it helped him. He also commented that his symptoms don't match up with PA and we should maybe consult an infectious disease specialist. He also offered him an antidepressant as did his GP. It was all so odd. That is why I'm asking so many questions because even the hematologist isn't fully convinced. It was the first thing we could hold onto that indicated he needed the B12. His extensive work up revealed IGG a little on the low side and Vit D completely in the tank. After 50K units twice weekly of D and 4 months of IVIG infusions his labs are normal but his symptoms didn't improve until the B12 injections. Frustrated and confused. I appreciate any and all insight! Thanks

[Hidden in reply to dll5602]

You won't find many doctors that understand that some people need more frequent B12 than others, it is very individual. I'm currently having twice weekly injections, as I recently added exercise back in and found I needed more (I was on weekly). There is some old research about short and long responders, but this kind of thing has been forgotten in modern medicine:

onlinelibrary.wiley.com/doi...

"differences between patients were very great, such that the entire trial with the three drugs was completed in 11 months in one case but lasted more than 4 years in another. Variation between patients makes it impossible to anticipate the duration of effect of a single injection of one of these drugs in any patient."

And as an aside, even if he didn't have classic PA he would have problems with B12 because of his lack of gallbladder. If you don't have a gallbladder the enterohepatic circulation of B12 is broken I think:

fao.org/docrep/004/y2809e/y...

"In addition to causing malabsorption of dietary vitamin B12, PA also results in an inability to reabsorb the vitamin B12 which is secreted in the bile. Biliary secretion of vitamin B12 is estimated to be between 0.3 and 0.5 µg/day. Interruption of this so-called enterohepatic circulation of vitamin B12 causes the body to go into a significant negative balance for the vitamin. Although the body typically has sufficient vitamin B12 stores to last 3-5 years, once PA has been established the lack of absorption of new vitamin B12 is compounded by the loss of the vitamin because of negative balance. When the stores have been depleted, the final stages of deficiency are often quite rapid, resulting in death in a period of months if left untreated."

[Leilanilea in reply to Hidden]

Hampster, Thanks for the older research links. Leilani

[KatyM in reply to dll5602]

that's really interesting - thanks for posting -

my daughter has all the neuro symptoms of B12 deficiency but her serum levels are apparently fine. The doctors here in Northern Ireland havent heard of 'Active B12' / Holotranscobalamin testing and are reluctant to refer her to consultant about it ...

Her vitamin D levels are obviously very low as we recieved a prescription in the post on Saturday for vit D supplements twice weekly, but still worried that the B12 serum test isn't picking up the 'active' B12, especially as during her pregnancy undiagnosed gallbladder problems were treated with Omeprazole and Renitidine - both bad for B12, and she had a long and difficult labour with gas and air - so lots of Nitrous Oxide - which inactivates B12.

But telling this to the docs is like talking to a brick wall

Thinking of getting Holotranscobalamin done at St. Thomas' if she isn't offered the test here, or just to keep asking for the injections ?

We have asked to see a haematologist but still not been referred ...

The way of dealing with the whole B12 issue is truly bizarre, when the D testing was done as a matter of course.

[dll5602]

Thank you. Why do all the other docs say IF doesn't matter? His labs show "ABNORMAL-EQUIVOCAL" which makes them all question the diagnosis. His IF didn't come back NEGATIVE....I know you said that still doesn't mean much, but it definitely wasn't NORMAL. His hematologist even said his labs were "screwy," but I've been beating on this drum for nearly a year and stumbled on using a B12 shot his mom gave me because she thought he needed it due to hemolytic anemia. His family has a rare, extremely genetic blood disorder called hemolytic spherocytosis. Most people with that disorder have their spleen removed because it begins to lose their efficiency in filtering blood and has the same type of symptoms as PA. His mother has been taking B12 twice a month for years due to that; however, my husband's spleen isn't failing yet according to many repeat labs. It appears he may have two types of anemia possibly working against him. His primary care doctor told us "he didn't buy it" and perhaps it's psychosocial!! The man couldn't get out of bed until I gave him a B12 shot. I was told he didn't need it because his serum is so high. MADDENING this process has been. He's been getting sick for 5 years and hit bottom nearly a year ago. He complains often of chills, muscle weakness, sometimes short of breath, dizziness, muscle wasting, and now his legs are falling asleep and he drags them sometimes. I was told this can't be due to PA....there has to be more going on but he's had the million dollar work up and nothing has helped. After a loading dose 2 months ago and weekly injections, he's recently been able to get up in the morning before noon, work hard, and he's beat by the evening. He says it's the best he's felt in 2 years, but neuro and FP say it doesn't make sense. I'm afraid he has neurologic damage due to this. His EMG came back abnormal and neuro said it's probably due to old accident. His accident was nearly 30 years ago and his symptoms have been creeping on for 5 years of tingling, numbness, etc. Thank you for the website. I've been scouring all information I can glean. I ordered the Pernicious Anemia book as well, but I don't ever stumble on a case like his with normal/high serum and IF of EQUIVOCAL.

[Hidden in reply to dll5602]

I guess I misunderstood what you meant, if you're saying his IF antibody result was abnormal then yes, he definitely has PA. It doesn't really matter what his serum B12 level is, that's just what you've got hanging around in the blood, as I've said above. It's not necessarily doing anything. In fact, the bit I said about the UKNEQAS warning could apply to your husband. The presence of IF antibodies can bring back a false normal serum B12 result in up to a third of those tested, a third!

This is the warning:

ukneqas-haematinics.org.uk/...

"“In the event of any discordance between clinical findings of B12 deficiency and a normal B12 laboratory result, then treatment should not be delayed. Clinical findings might include possible pernicious anaemia or neuropathy including subacute combined degeneration of the cord. We recommend storing serum for further analysis including MMA, or holotranscobalamin and intrinsic factor antibody analysis, and treating the patient immediately with parenteral B12 treatment.”

And this is the research:

nejm.org/doi/full/10.1056/N...

[helonlegs]

Hi dll5602

Not sure if you can help answer this question, but does your mother-in-law actually have B12 injections because of her spheracytosis and not because of PA or low B12? I have spheracytosis and have had both my spleen and gallbladder removed. My personal view was this would aggrevate my low B12 as this condition makes the red blood cells fragile and so not live as long, plus being destroyed by the body as abnormal - this is mostly done by the spleen which is why they remove it as you run out of blood. As B12 is needed by the body to make red blood cells, a deficiency of B12 in a condition where you need to make more blood cells than usual would cause more problems.

None of my GPs can answer this question and I do not see a haematologist - I was discharged at age 11 after my spleen removal and have never seen one in the 40 years since. I think that possibly I need to get referred to one so that I can get effective treatment.

I cannot find much about this on the web which is why I am asking you.

Thank you.

Helonlegs

[dll5602 in reply to helonlegs]

Spherocytosis is prevalent in my husband's family, and of those who have it, he is the only one who hasn't has his spleen removed (gall bladder came out in his early twenties). When he hit bottom nearly a year ago, we were all sure his spleen needed to be removed. After lots of labs, his hematologist said the disease wasn't worsening and his labs were perfect. His hemoglobin, reticulocyte count, and bilirubin were all normal. His mother doesn't have PA. They are definitely two different conditions. Without a spleen, you should be more cautious because your immune system is more vulnerable, and have a flu shot, pneumococcal vaccine, and certain vitamins. I'm not a doctor, but that's what I've picked up on through my family.