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Pernicious anaemia

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Urology

Neurological signs of B12 deficiency can be present even without anaemia. There is a 1–2% increased risk of thyroid disease or gastric cancer. Pernicious anaemia is best confirmed with an anti-intrinsic factor (IF) antibody test; the anti-parietal cell antibody test is less reliable.

About

An autoimmune cause of B12 deficiency leading to both haematological and neurological problems
Associated with a heightened risk of gastric cancer

Aetiology

Gastric parietal cells (which produce intrinsic factor and hydrochloric acid) are destroyed
This destruction is likely autoimmune; in certain cases, steroid therapy can reverse the inflammatory process

Physiology

A typical diet contains around 20 µg of B12 daily, while the body requires only 1–2 µg/day
B12 binds with intrinsic factor (IF) in the stomach and is absorbed in the terminal ileum
Once absorbed, B12 is bound to transcobalamin II in the portal circulation
The liver stores enough B12 to last for 2–4 years
B12 is essential for converting homocysteine to methionine

Clinical

Mean age of presentation is ~60 years; more common in individuals with fair skin and blue eyes
Possible mild splenomegaly and pallor
Vitiligo and a higher incidence of other autoimmune endocrine disorders (e.g., Addison’s disease, thyroid dysfunction)
Classical glossitis (“painful raw beefy tongue”) is a hallmark of B12 deficiency

Neurological Signs of B12 Deficiency

Optic atrophy and retinal haemorrhage
Dementia or cognitive impairment
Polyneuropathy: paraesthesia, distal sensory loss, and absent ankle jerks
Dorsal column dysfunction: loss of vibration and proprioception
Corticospinal tract involvement: extensor plantar responses, brisk knee jerks
Spinal cord lesions may become irreversible if not treated promptly

Investigations

Full Blood Count (FBC):Macrocytic anaemia (MCV >110 fL), possible very low Hb (4–5 g/dL) but often tolerated. May see anisopoikilocytosis, hypersegmented neutrophils, and low WCC/platelets.
Serum B12: Low (normal range 160–960 ng/L)
Serum Folate: Often low (normal range 4.0–18.0 µg/L)
Check Ferritin to exclude iron deficiency
Intrinsic Factor Antibody (IFAB) Testing: Highly specific but not very sensitive (~50% positive in pernicious anaemia). A positive IFAB result strongly indicates pernicious anaemia (PA). A negative result, however, does not exclude PA, especially in symptomatic cases or those showing a response to cobalamin therapy.
Anti-parietal cell antibodies can help support an autoimmune pattern but are not definitive and can be seen when PA is not present. They are not diagnostic.
Unconjugated hyperbilirubinaemia and elevated LDH may be present
Elevated Methylmalonic acid and homocysteine levels are highly suggestive of clinically significant deficiency, regardless of the underlying cause. They are non specific but suggest B12 deficiency.
Reticulocyte Count: Often low due to ineffective erythropoiesis
Endoscopy: May show atrophic gastritis with achlorhydria. Duodenal biopsy can help exclude coeliac disease if malabsorption is suspected.
Bone Marrow Aspirate (rarely needed):Would show megaloblastic changes in erythropoiesis.

Differential

Gastrectomy (leading to reduced IF production)
Atrophic gastritis (not always autoimmune)
Terminal ileal disease (e.g., Crohn’s) or resection
Poor diet (strict vegans) lacking adequate B12 intake

Management

Blood Transfusion: Generally avoid unless the patient is severely compromised. If necessary, proceed cautiously with diuretic cover to prevent volume overload.
Schilling test timing is not crucial; treatment should not be delayed.
Folate Deficiency Coexistence: Never give folate alone in the presence of B12 deficiency, as this may worsen neurological injury.
B12 Replacement: Give hydroxocobalamin 1 mg IM twice weekly for 3 weeks, then 1 mg IM every 3 months for life. Folate 5 mg once daily may be added if folate levels are also low.
When B12 therapy starts, there may be:
- Hypokalaemia (due to sudden erythropoiesis)
- Reticulocytosis peaking around day 4–7
- An initial slight drop in Hb before recovery
Ensure iron and folate levels are adequate before initiating therapy. A reticulocyte rise in 2–3 days indicates a good marrow response.

PLEASE NOTE LEGAL ADVICE: The contents are under continuing development and improvements and may contain errors of omission or fact. Feedback vital and always welcome at drokane at gmail.com. This is not to be used for the assessment, diagnosis or management of patients. It should not be regarded as medical advice. It is only for educational purposes. Please adhere to your local protocols. If you are unwell please seek healthcare advice from your doctor. This does not replace senior or specialist advice. If you do not accept this then please do not use the website. If you need medical advice, please consult a doctor or other appropriate medical professional. If you are a medical professional and you need advice then speak to your senior or colleagues.

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