Starting B12 treatment in those with macrocytosis +/- anaemia
- If the patient is anaemic or macrocytic request reticulocyte count and folate to help differentiate causes and as a baseline for assessing immediate response to treatment.
- Note that in severe B12 or folate deficiency, supplementation may cause severe hypokalaemia as red cell reproduction restarts and a U&E check after starting treatment may be appropriate
- Check reticulocyte count again within 7–10 days of starting treatment if initial haemoglobin and reticulocytes low. An increase in the reticulocyte count to above the normal range indicates that treatment is having a positive effect and red blood cell production is appropriately increasing
- Repeat FBC and reticulocyte count at 8 weeks. The mean cell volume (MCV) should be normalising, and reticulocyte count rising. If the reticulocyte count is still low, please see the RefHelp macrocytosis guideline as a haematology referral may be needed.
Example reticulocyte ranges:
- Low < 25 (often seen in low B12 / folate)
- Normal 25-85
- Raised > 85
Vitamin B12 deficiency and immunological testing.
Traditionally, two immunological tests have been associated with assessing B12 status, but they are both potentially problematic:
- Intrinsic Factor antibody (IFAB) is poorly sensitive: IFAB may be absent in up to 40-50% of patients with pernicious anaemia, but positive IFAB is highly specific for pernicious anaemia.
- Gastric Parietal Cell Antibodies are also not fully sensitive and are poorly specific so checking these is not always useful. Please note that if you do order gastric parietal cell antibodies, they form part of a linked test array, so your patient will automatically also be tested for anti-mitochondrial antibodies (AMA), Smooth muscle antibodies and LKM1 antibodies – which are all associated with autoimmune liver disease.
In those who have low B12 levels, but no clear cause, the diagnosis of IFAB negative pernicious anaemia therefore relies on clinical evaluation e.g. patients who fail to respond to oral B12 therapy following adequate replacement over at least 6 months (where IM B12 is not immediately indicated for other reasons).
In an individual where pre-test probability for pernicious anaemia is high (e.g. an older woman with a history of autoimmune diseases) a negative IF antibody result is more likely to be a false negative than in someone where pre-test probability is low (e.g. where there is an alternative explanation for B12 deficiency).
C.M & A.K. 01-08-25
