treatment of vitamin B12 deficiency

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Blood transfusion is rarely indicated for a vitamin B12 deficiency except in severe anaemia or where other causes of anaemia such as bleeding, coexist. Transfusion carries the danger of fluid overload, particularly in the elderly (1,2).

B12 deficiency is generally treated with vitamin B12 supplementation.

  • if B12 levels are particularly low then intramuscular B12 should be given and a haematology referral made (1)
    • treatment of pernicious anaemia and other macrocytic anaemias with neurological involvement - five to six loading doses of 1000 mcg over a period of one to two weeks followed by 1000 mcg every three months (see BNF for full details)
  • if B12 levels are borderline then response to oral B12 may be diagnostic and management should be discussed with the local haematology department (1)
    • treatment of vitamin B12 of dietary origin, cyanocobalamin 50-150 mcg daily in 1-3 divided doses (see BNF for full details)

Patients generally feel better within 24 to 48 hours of starting treatment by which time normal haemopoiesis is established in the marrow. The blood reticulocyte count usually rises after a week paralleled by the platelet count, which may rebound temporarily to abnormally high levels. Response may be slower if there is coexistent disease.

A more detailed treatment algorithm is summarised (1,2,3,4):

If Serum vit B12 > 200 then Normal level: no further investigation needed

If Neurological symptoms:

  • If Leber's optic atrophy or tobacco amblyopia then:
    • Hydroxocobalamin 1000μg IM daily for 2 weeks then 2x/week until no further response then every 3 months lifelong and investigate for underlying cause

  • If peripheral neuropathy, dementia then:
    • Hydroxocobalamin 1000μg IM 3x/week for 2 weeks and then every 3 months lifelong and investigate for underlying cause

If Serum vit B12 > 150 and asymptomatic then:

  • recheck serum vit B12 level after 2 months
  • if the repeat level is still low, a significant proportion of these patients will go on to develop symptomatic vitamin B12 deficiency in the future. There a choice of:
    • (1) monitor the vitamin B12 level on a 6 monthly basis for 12 months and then on an annual basis or
    • (2) treat with oral vitamin B12 supplements and monitor the serum vitamin B12 level and FBC after 2-3 months to see if it improves - this is the initial management option that is likely to be the most employed in the primary care setting for asymptomatic B12 deficiency rather than monitoring alone
  • NB this option explained in more detail below

If Serum vit B12 < 150 and macrocytosis +/- anaemia [if pancytopenia discuss with haematologist]

  • if evidence of pernicious anaemia (anti-GPC (gastic parietal cell) or esp. anti-IF (intrinsic factor) Abs positive) then:
    • Hydroxocobalamin 1000μg IM 3x/week for 2 weeks and then every 3 months lifelong - diagnosis of PA (pernicious anaemia ) is inferred
    • note in Pernicious anaemia there is evidence that high dose oral vitamin B12 therapy taken daily has similar efficacy in improving symptoms and haematological parameters of B12 deficiency - however, it is not preferred for initial treatment of patients with severe symptoms because of the possibility of slower response compared with intramuscular injection
      • has been stated that oral therapy may be used for long term maintenance treatment in pernicious anaemia (4)
      • with adequate B12 replacement:
        • reticulocyte count usually increases and peaks at one week
        • within 8 weeks - resolution of anaemia and normalisation of macrocytosis
        • if neurological involvement then recovery is generally slower and less predictable

  • if no evidence of pernicious anaemia then:
    • consider other causes of vit B12 deficiency e.g. malabsorption, drugs, dietary
      • if malabsorption: Hydroxocobalamin 1000μg IM 1-3x/week (depending on severity of deficiency) for 2 weeks and then every 3 months lifelong
      • if dietary: try oral vit B12 50- 100μg daily and recheck serum vit B12 and FBC (to see if MCV +/- anaemia has corrected) after 2 months (3)

    • if no evidence of B12 deficiency relating to either malabsorption, drugs, dietary then reassess that have considered other causes of macrocytosis +/- anaemia unrelated to vitamin B12 deficiency e.g. liver dysfunction, folate deficiency, hypothyroidism, haemolysis, myelodysplasia, antimetabolite drugs etc.
      • if above excluded, consider treating with vit B12 50-100μg PO daily and recheck serum vit B12 and FBC (to see if MCV +/- anaemia has corrected) after 2 months. If still no response, try Hydroxocobalamin 1000μg IM 1-3 x/week (depending on severity of deficiency) for 2 weeks, recheck FBC and vit B12 after 4 weeks and consider referral to Haematologist (3)

If Serum vit B12 < 150 and NO (macrocytosis +/- anaemia) then:

  • consider treating with vit B12 50-100μg PO daily and recheck serum vit B12 and FBC after 2 months OR
  • Hydroxocobalamin 1000μg IM 1-3x/week (depending on severity of deficiency) for 2 weeks and then every 3 months lifelong OR
  • monitor serum vit B12 level every 6 months for 1 yr then annually for 2-5 yrs (3)

Management of asymptomatic B12 deficiency (3):

  • management of patients with apparently asymptomatic vitamin B12 deficiency is a source of considerable debate
    • these patients usually have a serum vitamin B12 >150ng/l
      • worth confirming the 'deficiency' by repeating the serum vitamin B12 level (beware: the laboratory computer system may automatically reject requests for vitamin 12 levels within 42 days of the previous request- make it clear on the request form why you are repeating the test in a short time-frame)
    • if the repeat level is still low, a significant proportion of these patients will go on to develop symptomatic vitamin B12 deficiency in the future. There is then have a choice:
      • (1) monitor the vitamin B12 level on a 6 monthly basis for 12 months and then on an annual basis or
      • (2) treat with oral vitamin B12 supplements and monitor the serum vitamin B12 level and FBC after 2-3 months to see if it improves - this is the initial management option that is likely to be the most employed in the primary care setting for asymptomatic B12 deficiency rather than monitoring alone
      • an initial strategy of treating these patients with parenteral vitamin B12 supplementation would seem somewhat heavy-handed (3)

Notes:

  • if there is associated low red cell folate levels and dietary deficiency is unlikely then refer to exclude chronic inflammatory or malabsorption states (1)
  • evidence derived from limited studies suggests high doses of oral vitamin B12 may be as effective as intramuscular administration in obtaining short term haematological and neurological responses in vitamin B12 deficient patients (2)
  • there is no need to monitor serum vitamin B12 levels in patients receiving 3 monthly parenteral vitamin B12 treatment (3)
  • it has been suggested to add folic acid 5mg PO daily for 4 weeks for patients with anaemia due to vitamin B12 deficiency. This avoids the possibility of inducing folate deficiency consequent upon the increased normoblastic red cell production that should follow after providing a source of the previously deficient vitamin B12 (3)
  • hydroxocobalamin has replaced the use of cyanocobalamin as the form of vitamin B12 of choice for parenteral therapy: it is retained in the body for longer than cyanocobalamin (3)
  • the rationale for treating patients with apparently asymptomatic but significantly reduced levels (<150ng/l) of serum vitamin B12 is that some of these patients show biochemical evidence of subclinical vitamin B12 deficiency e.g. increased levels of plasma homocysteine and methylmalonic acid and some will develop symptomatic problems if left untreated
  • patients treated with oral repletion therapy need to have their initial response to treatment monitored with vitamin B12 levels after 2-3 months followed by 6-12 monthly tests to ensure an ongoing response
  • gastroscopy is recommended initially in patients diagnosed with pernicious anaemia for the diagnosis of atrophic gastritis and for evaluation of gastric malignancies (4)

Reference:

  1. Pulse 2004; 64(35):88.
  2. Vidal-Alaball J et al. Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. Cochrane Database Syst Rev 2005;(3):CD004655.
  3. Royal United Hospital Bath NHS Trust. Guidelines for the Investigation & Management of vitamin B12 deficiency (accessed 25/4/2020).
  4. Mohamed M et al. Pernicious anaemia. BMJ 2020;369:m1319.

Last edited 04/2020 and last reviewed 10/2020

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