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Pernicious Anaemia, B12, and Folate Deficiency

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Overview

Pernicious anaemia is an autoimmune condition where there is reduced production of intrinsic factor (IF) which is necessary for vitamin B12 (cobalamin) absorption. Normally, IF is produced by gastric parietal cells and binds to B12 to form IF-B12 complexes. IF facilitates the absorption of B12 in the distal ileum.

Pernicious anaemia is the most common cause of severe vitamin B12 deficiency in the UK.

It may be helpful to look at the chapter on Anaemia: Data Interpretation alongside reading this section to help wrap your head around when to suspect what type of anaemia.

Epidemiology

  • Pernicious anaemia is the most common cause of B12 deficiency in the UK
  • Pernicious anaemia occurs mostly in people aged 40-70 years
  • Mean age of onset for people of Black ethnicity is 50 years
  • Prevalence is around 5 per 100,000 per year

Causes of B12 Deficiency

  • Pernicious anaemia
  • Drugs:
    • Colchicine
    • Metformin
    • Nitrous oxide
    • Proton pump inhibitors
    • H2-receptor antagonists
  • Gastrectomy or gastric bypass surgery
  • Coeliac disease
  • Crohn’s disease
  • Parasites e.g. giardiasis
  • Malnutrition
  • Strict diets e.g. vegan diets

Example History

A 40-year-old woman has a 3-month history of progressive fatigue. She has pins and needles in both legs without any weakness. An examination is unremarkable except for her appearing pale.

Investigations:

Haemoglobin:75 g/L(115 – 165 g/L)
Platelets:230 x 109/L(150 – 450 x 109/L)
White blood cells (WBC):5.3 x 109/L(3.0 – 10.0 x 109/L)
Serum B12:83 pg/mL(180 – 1000 pg/mL)
Serum folate:1.3 ng/mL(>4.0 ng/mL)
Intrinsic factor antibodies:Positive(Negative)

Presentation

Patients present with the following:

  • Features of anaemia:
  • Neurological signs and symptoms:
    • Paraesthesias – “pins and needles”
    • Decreased vibration sense
    • Mood disturbances
    • In later stages: hyporeflexia, weakness, spasticity, ataxia
  • Angular cheilitis – cracked and painful sores at the corners of the mouth
  • Glossitis – swollen and inflamed tongue
  • ‘Lemon tinge’ to the skin

Investigations

All patients

  • Full blood count (FBC):
  • Reticulocyte count:
    • Used to screen for haemolytic anaemia
    • Usually low, unlike haemolytic anaemia where it would be raised
  • Blood film:
    • Shows hypersegmented polymorphonucleated megalocytes i.e. megaloblastic macrocytic anaemia
  • Serum B12:
    • Reduced
  • Serum folate:
    • May also be reduced
  • Intrinsic factor antibody:
    • Positive in pernicious anaemia

Management

All patients

  • 1st-line: intramuscular (IM) B12 replacement (hydroxocobalamin) followed by folate replacement (if necessary)
    • Always treat B12 BeFore Folate due to the risk of subacute combined degeneration of the cord
    • B12 is not given orally. If patients have pernicious anaemia, they cannot absorb the B12 from the gut, therefore it is given IM.

Monitoring

  • Patients should have an FBC and reticulocyte count:
    • Within 7-10 days of treatment to assess their response
    • After 8 weeks, measure iron and folate levels, the MCV should have normalised
  •   After folate has been replaced

Patient Advice

  • For patients whose B12 deficiency is due to diet, they should aim to eat foods rich in B12 e.g. eggs, meat, milk, fish, and foods fortified with B12 such as cereals and bread.
  • Neurological recovery usually starts within a week and recovers completely between 6 weeks and 3 months

Complications

  • Pernicious anaemia is associated with a higher risk of developing gastric cancer and other autoimmune diseases
  • B12 deficiency complications:
  • Folate deficiency complications:
    • Prematurity in pregnancy
    • Increased risk of neural tube defects in pregnancy

Prognosis

  • Prompt replacement of B12 and folate leads to a normal lifespan
  • If the deficiency is severe and prolonged, neurological complications may be irreversible

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