Please help

[Simonapo]

Hi, I have posted here about my mom few months back. She had her second bone marrow biopsy and they found everything normal, she had been taking sublingual B12 and Folic Acid for several months already with no sign of improvement, now she needs blood transfusions every other week. I am beyond worried, I don’t understand what could be wrong, I took her to 4 hematologists and had tons of testing done over the past 8 months and she still has no diagnosis and no treatment. Anybody out here in similar situation, I am desperate and don’t know what to do to help her out. Any advice is greatly appreciated. Thank you so much.

[Technoid]

MCV still very elevated? How are liver tests looking? What's prompting the transfusions?

[Simonapo in reply to Technoid]

MCV were still elevated at around 114, the hemoglobine dropped to 6.5 and they gave her blood transfusion. They are checking it every other week and it keeps going back down to 6.5-6.6 and they give her more blood transfusion. No fever, no symptoms at all except being tired. Her liver and kidneys and all the other blood result are good, she never drank alcohol.

[FlipperTD]

Scientist, not medic.

It's unusual to have a 'no abnormality detected' on a bone marrow if the Hb is dropping like that and it's macrocytic too. I would have expected that it would show megaloblastic erythropoiesis and be hypertrophic. A couple of questions to consider asking the haematologist.

Could this be sideroblastic anaemia? [rare but can be confusing]

Can we try B12 injections?

Can we do a reticulocyte count on the next CBC before transfusion?

Good luck with this. I hope you can find an answer.

[Simonapo in reply to FlipperTD]

Thank you so much for your reply, please see findings of bone marrow biopsy: “COMMENT: The current bone marrow is normocellular for age with an average cellularity of 30% (range 20-50%). There is evidence of active trilineage hematopoiesis with mildly increased myelopoiesis, mildly decreased erythropoiesis, and adequate megakaryocytes. Plasma cells are estimated at 3-4% of cells and show minimal clustering, IgM-restricted heavy chains, and lambda-predominant light chains. Blasts are not increased by morphology, flow cytometry, or immunohistochemistry. Although occasional erythroid precursors with mild nuclear irregularity and few megakaryocytes with hypolobated/monolobated nuclei are seen, there is no overall evidence of myelodysplasia. Few small to intermediate-sized, well-circumscribed reactive lymphoid aggregates are identified on the clot sections. Iron stores are adequate to slightly increased. No ring sideroblasts are identified. There is no increase in reticulin fibrosis. No myeloma- or myelodysplasia-associated abnormalities are detected by the concurrent cytogenetic and molecular studies detailed below. Clinical correlation is required.”

Also Reticulocyte count was 1.7 ( normal) in April, 3.2 in May ( high) and 0.3 ( low) in November.

I suggested to try B12 injections every day for one week but none of the 4 hematologists that I took her to want to give her B12 injections, they are saying that sublingual should work.

Please, please let me know your opinion, thank you SO MUCH.

[B12life in reply to Simonapo]

If her liver and kidney function is good, I see no reason not to inject.

what is or was her lowest b12 level?

[Simonapo in reply to B12life]

Thank you B12 was 300.

[B12life in reply to Simonapo]

Dang that's low. The problem she is having is that doctors, and hematologists esp, don't understand that you can be in the range but still have symptoms.

Read this article. the table on the 2nd page lists all the misconceptions doctors have about b12 and how frequent the b12 is ignored.

mcpiqojournal.org/article/S...

I think she should find a way to self inject and start self injecting daily or eod until she gets feeling better.

B12 gets depleted very slowly (3-4 years) and thus symptoms come on so subtly and gradually. thus it may take her 1-2 years of injections to start feeling better. you can ask on this forum this question so people with similar experience of depletion due to diet can give you their timelines. She doesn't have to eat meat, just supplement with b12. Once she gets the levels back up via the injections, she can switch to oral. After the 1st injection, b12 tests are not reliable as the injection skews the level. (also mentioned in the article above). Thus you must base progress on symptoms.

B12 is not toxic at any dose or frequency as long as she has a healthy liver and healthy kidneys, which she has.

Seek out a doctor who will listen, show you how to inject. Explain that she didn't eat meat and got depleted and is not able to raise her b12 and just needs help getting the level up through injections.

Also there is a template that PAS has information justifying b12 injections. You can submit this letter to your doctor. but honestly ask this forum if anyone knows a good doctor in your mother's area that understands b12.

Sleepybunny - do you know where this letter is.

B12 may not be her only problem, I would keep what FlipperTD mentioned in mind always. But additionally get the b12 levels up through injections.

If b12 isn't treated, symptoms can become permanant (also in that article), so it's important to get the injections started for her to reverse the deficiency, then she could possibly go on oral after 1-2 years of injections or whenever her symptoms resolve.

[Simonapo in reply to B12life]

Thank you so much, much appreciated 🙏

[Sleepybunny in reply to B12life]

Hi B12life,

B12info.com website has letter templates.

b12info.com/writing-to-your...

Some of the info is specific to UK.

PAS has lots of useful leaflets.

Some of the info may be specific to UK.

pernicious-anaemia-society....

[FlipperTD in reply to Simonapo]

Fascinating. Something's causing this, isn't it, but the marrow seems to be as you say.

They're right that sublingual should work, but not necessarily. It surely couldn't harm to try injections as you say, and then a retic count after a week. That should show whether it's working or not. Especially if the patient is anaemic.

Please note, I'm a scientist, not a medic, but this was my area.

[Simonapo in reply to FlipperTD]

Thank you, do you believe one week if daily B12 injections should show if it’s working or not, is one week enough to tell? Thank you again.

[FlipperTD in reply to Simonapo]

The bone marrow will usually respond quite quickly when it's B12 deficient, if you're on B12 injections. In iron deficiency it takes a bit longer, but daily B12 injections ought to produce a retic response inside about five days.

There's a lot of guesswork in all of this, and sometimes it can be the best way, but injections and retic counts after a few days should do the job. It takes a good while longer for the results to approach normal, but the retic count is a good early indicator.

[Simonapo in reply to FlipperTD]

Thank you so much.

[B12life]

is she vegetarian or does she eat meat daily?

[Simonapo in reply to B12life]

She eat plant based diet for 3 years before the hemoglobin started dropping. She stopped right away and started eating regular food. The doctors believe that because she has been eating meat lately and taking sublingual B12 without any increase in Hemoglobin , contrary there is a decrease, B12 is not the cause?

[Technoid in reply to Simonapo]

"She stopped right away and started eating regular food."

Always makes me sad when someone encounters a health issue while eating plant-based and immediately thinks that eating animals is the solution.

If it's a B12 issue, even if it's a functional deficiency, injections will do the trick, with time.

[Simonapo in reply to Technoid]

Thank you.

[B12life]

what is the dose of b12 that she is taking currently

[Sleepybunny]

"She had her second bone marrow biopsy and they found everything normal, "

Have you and your mom been able to look at the results?

I always try to check for myself.

I can see you've posted some of the results already.

[Simonapo in reply to Sleepybunny]

Thank you for your reply. Yes those are the results, they said it shows normal process of bone marrow, they have no idea what is causing my mom’s anemia after 2 bone marrow biopsies, PET scan, colonoscopy, endoscopy and 100 blood test, all normal with the exception of anemia.

[Sleepybunny]

I was symptomatic for B12 deficiency for years but couldn't get treatment because all but one of my serum B12 results were well within normal range.

When I finally started B12 treatment, it took months of regular B12 injections to start seeing improvements because I had been left untreated for so long. I tried high dose oral B12 (1000mcg or higher) but it did very little for me.

What strength oral B12 is she taking?

[Simonapo in reply to Sleepybunny]

She takes sublingual 2000 mg..

[Sleepybunny]

I can see you posted some results from complete blood count (CBC) in your older thread.

Do you have a result for eosinophils, a type of white blood cell?

The reason I'm asking is that one potential cause of low B12 and low iron is an internal parasite eg fish tapeworm

Internal parasites can lead to a raised eosinophil result.

If you have time, search online for "human parasite low haemaglobin".

Medical and health articles may have details that could be upsetting.

Has she ever been tested for lyme disease and co-infections eg babesiosis?

Lyme disease and its co-infections can be associated with low haemaglobin.

I think you mentioned in a previous thread that her ferritin levels were above normal range.

There are lots of possible reasons for raised ferritin including

inflammation in the body

a genetic condition called haemachromatosis

Have you researched "complete blood count" online?

Testing.com link about Complete Blood Count

testing.com/tests/complete-...

Testing.com links about iron tests

testing.com/tests/iron/

testing.com/tests/ferritin/

testing.com/tests/transferr...

Have her doctors looked into the possibility of functional B12 deficiency?

This is where there is plenty of B12 in the blood but it's not getting to where it's needed in the cells so person develops deficiency symptoms.

MMA, Homocysteine and Active B12 (holotranscobalamin) tests can help to diagnose functional B12 deficiency.

[Simonapo in reply to Sleepybunny]

Thank you so much for all the good info, she was not tested for Lyme or functional B12. Her Neutrophils is normal please see attached, thank you very much.

Results

[Sleepybunny in reply to Simonapo]

I made a mistake Simonapo, it's eosinophils that can be raised if internal parasite is present. I've corrected my other reply to show this.

Search online for "parasite eosinophilia" for more info.

[Simonapo in reply to Sleepybunny]

I checked the absolute eosinophil and the % are both normal, thank you.

[Sleepybunny in reply to Simonapo]

I can see MPV (mean platelet volume) is only just within normal range.

Do you know what the platelet result is?

UK link about Full Blood Count (aka Complete Blood Count) - hopefully you can access this.

labtestsonline.org.uk/tests...

I found some interesting articles when I searched online for "blood indicators parasitic infections".

Has she ever had a blood smear (also known as blood film)?

testing.com/tests/blood-smear/

[Simonapo in reply to Sleepybunny]

Platelets are normal

Results

[Sleepybunny in reply to Simonapo]

Hi,

I looked up RDWCV and I think it means Red Blood Cell Distribution Width (sometimes RDW is used)

RDW results that are above range suggest abnormal variation in RBC size.

This could mean iron, B12, folate deficiencies or problems with bone marrow.

B12 deficiency can lead to red blood cells that are larger than normal (macrocytosis).

Folate deficiency can lead to red blood cells that are larger than normal (macrocytosis).

Iron deficiency can lead to red blood cells that are smaller than normal (microcytosis).

Sometimes the effect of iron deficiency masks the effect of B12 deficiency (and/or folate deficiency) on red blood cells.

I hope the doctors carry out a blood smear (blood film) if they haven't already.

This could confirm if she has a mix of microcytic cells and macrocytic cells.

Low MCHC can suggest a lack of haemaglobin in cells, maybe caused by anaemia.

I searched online for "causes low MCHC" and found other possible causes of low MCHC.

If you have time, perhaps you could compare the most recent Complete Blood Count results with those taken in past and look for trends in the results.

Is anything increasing or decreasing over time?

This could be significant even if results are within normal range.

[Simonapo in reply to Sleepybunny]

Thank you for trying so hard to help out, I really appreciate it, I will ask for a blood smear and try to look at all CBC results if I can find any movements. Thank you again.

[FlipperTD in reply to Sleepybunny]

Scientist showing off: only read if you're really interested!

The relationship between MPV and Platelet Count is complicated. It's an inverse, non-linear relationship. This means that you can't simply report whether the MPV is high or low; it needs to be reported with the relationship to the platelet count. The higher the platelet count, the lower the MPV range.

The RDW is a measure of variation in the size of the red cells. If you're transfused with someone else's red cells and your MCV is raised, then the 'normal' red cells will widen the size range of circulating red cells, as you've got a mixture of big and normal, so the RDW would be expected to rise.

In most cases of anaemia, then I'd expect the RDW to be increased.

In many circumstances, I'd be suspicious of the MPV because as platelets are sitting in the sample tube awaiting counting, they're surrounded by the EDTA anticoagulant, and that has a tendency to make the platelets swell, so the MPV rises as a storage artefact. The platelet count is far more important than the MPV.

The MCHC once upon a time was one of the few derived values we had, and relied upon a centrifuged PCV [microhaematocrit]. Nowadays, the PCV is derived from the directly measured MCV and the red cell count. Then this is divided into the Hb, and 'hey presto' we have an MCHC, which is similar to the 'old fashioned' MCHC but not quite the same. Plus delays in processing can interfere with the reliability, depending on which method the analyser uses. [That's for another time.]

I hope this isn't too confusing.

[Simonapo in reply to FlipperTD]

Cant thank you enough for taking the time to explain everything. Thank you very much.

[FlipperTD in reply to Simonapo]

Her neutrophil count may be normal, but in B12 deficiency we see hypersegmented neutrophils down the microscope. This is when the neutrophil nucleus has more than the usual number of segments. It is also, historically, described as a 'right shift' for reasons I could elaborate on, but won't at the moment. I already ramble quite enough!

[Simonapo in reply to FlipperTD]

Very impressed with your knowledge, thank you for everything.

[FlipperTD]

It really isn't a problem sharing what I've learned over the years; you're more than welcome.