which discuss patients with PA having normal

[alanlock]

came across article in British Medical Journal, BMJ 2020;369:m1319, which discuss patients with b12 deficiency and normalcytic anemia, whcich I'am assuming is very similar to PA. resulting in a missed diagnosis of b12 deficiency. is anyone aware of similar work/opinions? also what is relationship between normalcytic anemia and PA? cheers alanlock

[fbirder]

It's a total myth that people with PA must have macrocytic anaemia. There are two main reasons why they may not.

Macrocytosis is one of the last symptoms to appear after a B12 deficiency.

People with PA often have an iron deficiency. Iron deficiency anaemia results in small red cells (microcytosis). B12 deficiency anaemia results in large red cells (macrocytosis). When they measure the average size of red cells (the MCV, Mean Cell Volume) they find that the average of big and small is 'normal'.

For a reference - discoverymedicine.com/Thein...

Macrocytosis is absent in about 30% of PA patients (Carmel, 1988; Healton et al., 1991). Any diseases which cause microcytosis, e.g., iron deficiency anemia (IDA) if coexisting with PA, may result in normocytic anemia. In extreme scenarios, PA may present with microcytosis. Approximately 20.7% of PA patients have coexisting IDA at the time of diagnosis. Another 22.3% of PA patients develop IDA one month to 14 years later (Carmel et al., 1987). Other authors have found that 42% of African Americans and South Africans with PA have no macrocytosis; some were found to have IDA after the cobalamin replacement (Solanki et al., 1981).

[alanlock in reply to fbirder]

thanks for that. so does this mean that the relevant blood tests will always show a low b12 reading in patients being tested for PA? thus helping to ensure that PA patients will not be 'missed'.?

[fbirder in reply to alanlock]

No.

A serum B12 test can still miss lots of people who have a B12 deficiency, despite having 'normal' levels.

[Gambit62 Administrator in reply to alanlock]

serum B12 tests can be useful if they show a significant drop over time - as the test isn't that accurate that means drops of 20% plus or a steady downward trend - however it is extremely rare to see the test used in this way and GPs almost exclusively use it as a single point test without reflecting on the enormous normal range and how that might operate.

People do vary enormously in the point in the range which is right for them but using stores in the liver helps them to keep serum levels pretty constant. However, an absorption problem also affects the efficiency of this release mechanism resulting in gradual falling of serum levels. It can take years and even decades for the stores to be depleted and levels to fall to the bottom of the normal range - particularly if someone naturally sits at the top of the range - the symptoms of PA develop slowly over this time and this may be slow enough for people not to realise that they are developing unless they reflect back ... and there is also a tendency to put things down to 'getting older'

[alanlock in reply to Gambit62]

thanks for that. my wife has PA. due to our surgery's approach to prioritising patients during covid-19 they delayed all b12 injections for 3 months. it has taking 6 weeks for us to get them to agree giving the b12 injection. however during a tel conversation with her GP he said her blood levels, 2 days prior to last b12 injection, (5 and a half months ago) were higher than a 'normal' person i.e. without PA! I guess I'am looking for an explanation as to how a PA patient can have normal b12 levels and have PA symptoms.

[Gambit62 Administrator in reply to alanlock]

I don't think there really is an explanation at the moment - just various theories. Unfortunately though GPs are rather hooked on serum B12 as an indicator when basically it is nothing of the sort post B12 injections. The injection itself will raise serum B12 levels to astronomic levels and they then fall over time. In some early studies some patients took many years for serum B12 levels to fall back for to normal range. Serum B12 tells you what is happening in the blood but it doesn't actually tell you what it is happening at the cell level. Unfortunately raising serum B12 levels seems to be a trigger in some people for something that effectively means the

process that transfers B12 from blood to cells gets less efficient. This happens even in patients who haven't had injections but whose serum B12 levels may be raised as a result of other problems - such as liver and kidney problems resulting in high serum B12 levels but all the symptoms of B12 deficiency (a phenomenon known as functional B12 deficiency). This can generally be detected by looking for raised levels of metabolites that can't be recycled unless the cell has enough B12 (MMA and homocysteine) but both can be raised by other factors). Whatever it is that affects the transfer from blood to cell also seems to make the processes that generally remove excess B12 from your blood less efficient as well so the serum B12 levels just stay high much longer.

Basically the biochemistry of B12 in someone who has had raised serum B12 can be very different from the biochemistry where this hasn't happened. It doesn't apply to everyone but it does apply to a significant number of people. Exact causes not understood.

[alanlock in reply to Gambit62]

thanks for the comments and information