Diagnosing Vitamin B12 Deficiency and Pernicious Anaemia

From the very beginning this charity has been made aware that there are serious problems with patients receiving an early diagnosis that will explain their symptoms. The problem of getting an accurate and quick diagnosis were the subject of many discussions on social media and on our online forum and its extent became clear when the results of our survey 1 were published.
We asked over a 1,000 of our members whether they were given an initial false diagnosis and how long they had experineced symptoms before being diagnosed.
48% were initially wrongly diagnosed as having some other problem.

22% had to wait 2 years for a correct diagnosis

More than 21% had to wait for 5 years

5.5% for 10 years

Almost 16% waited 10 years or more.

PA diagnosis

There are several reasons why there are problems with patients getting quickly and accurately diagnosed

The problems with diagnosing Pernicious Anaemia begin with the issues surrounding diagnosing B12 Deficiency; these are outlined below:

  1. There is no consensus of what constitutes a Vitamin B12 Deficiency. Some commentators believe that the current reference level used to determine a deficiency is too low and needs to be raised 5
  2. Doctors are not ‘looking’ for B12 Deficiency. That’s why it’s important that you ask your doctor to check your B12 levels.
  3. There are serious shortcomings with the current test used to determine B12 status in patients. The current test, the Combined Binding Luminescence Test is giving false high results in between 22 and 35% of patients (depending on the manufacturer of the test machine). 6 If your test results come back as normal or borderline you may want to ask your doctor for a Therapeutic Trial of B12 injections to judge whether you feel better.
  4. Different laboratories set different thresholds to determine a deficiency. This means that in one area of the country your test results might indicate a deficiency whereas in another area you wouldn’t be considered to be deficient5. This makes diagnosing any deficiency dependent on your postcode.
  5. There is an even greyer area with sub-clinical deficiency – a deficiency even though the patient’s B12 status is above the normal threshold for determining any deficiency.
  6. B12 status is not part of the Full Blood Count that is routinely investigated by doctors. Instead most doctors will rely on enlarged red blood cells (megaloblasts) as being an indicator of low B12. However, only around 60% of patients with a B12 deficiency will have enlarged red blood cells (macrocytosis) 2, 3 , therefore a normal MCV does not rule out a B12 deficiency.
    Neurological symptoms due to cobalamin deficiency may occur in the presence of a normal MCV 5. Ask for your B12 to be tested if your full blood count doesn’t show any signs of enlarged red blood cells.
  7. If you are taking any sorts of B12 Supplement (such as a multivitamin tablet) do tell your doctor about this. Also, be aware that taking folic acid will prevent your red blood cells becoming enlarged so be sure to tell your doctor if you are taking any form of folic acid.


The Guidelines on Cobalamin and Folic Acid by the British Committee for Standards in Haematology 5 state the following:

  • The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status since there is no ‘gold standard’ test to define deficiency.
  • Definitive cut-off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established.
  • In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment.

Whatever the outcome of the tests it is a good idea to ask for a copy of the results so that you can make an informed decision about your next step – the treatment.

Key Points:

  • Some doctors believe that the current threshold for determining B12 Deficiency is far too low 6 and that there is a link between the speed of brain shrinkage and B12 levels.7
  • You cannot overdose on vitamin B12 as it is a water soluble vitamin.

When you go to your Health Professional it will be useful for you to go fully informed. So please feel free to use the items we have created below.

We have an ‘Update for Health Professionals‘ leaflet and ‘Helpful Info for your GP/Consultant’ available in our members-only library with more information for your GP/Consultant.

Testing for Pernicious Anaemia , suggestions for you and your GP – It will be useful for you to print and read this.

Symptom Checklist (PDF) – This is useful to print, read and fill in.

  1. May 2014
  2. Patient Journeys: diagnosis and treatment of Pernicious Anaemia: Hooper M V, Hudson P, et al; British Journal of Nursing, 2014, Vol. 23, No 7
  3. Beck W S. Neuropsychiatric consequences of cobalamin deficiency. Advanced Institute of Medicine, 1991; 36: 33-56
  4. Lindenbaum J, Healton EB et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. New England Journal of Medicine 1988; 318(26): 1720-1728
  5. Devalia V, Hamilton M, Molloy A; Guidelines for the Diagnosis and Treatment of Cobalamin and Folate Disorders; British Journal of Haematology,2014,166,496-513
  6. Carmel R, Agrawal Y P. Failures of Cobalamin Assays and Pernicious Anaemia. New England Journal of Medicine, 2012, 367(4): 266.
    See also David T. Yang, Rachel J. Cook, Spurious Elevations of Vitamin B12 with Pernicious Anemia: New England Journal of Medicine; 366;18
  7. Smith & Refsum; Do We Need To Reconsider Blood Level of Vitamin B12?  Journal of Internal Medicine, 2012;271(2): 179-182
  8. Douaud G, Refsum H, et al: Preventing Alzheimer’s disease-related gray matter atrophy by B-vitamin treatment http://www.ncbi.nlm.nih.gov/pubmed/23690582

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