Megaloblastic Anaemias

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Vitamin B12 Deficiency

Causes

1. Inadequate dietary intake – B12 is found in diary, eggs, meat, and fish. Vegans may have B12 deficiency as a result.

2. Malabsorption

• Pernicious anaemia – autoantibodies against gastric parietal cells or intrinsic factor

  • Gastric parietal cells produce intrinsic factor. Intrinsic factor binds to B12 from ingested food to form a complex. This complex is absorbed at the terminal ileum. Therefore without intrinsic factor, B12 can not be absorbed into the blood, resulting in deficiency.

• Gastrectomy – loss of the parietal cells of the stomach would lead to decreased intrinsic factor production.

• Disease of the terminal ileum – Crohn’s disease most commonly affects the terminal ileum, which would impair its ability to absorb B12. Additionally, surgical resection of the ileum would cause B12 deficiency for the same reason.1

 

Clinical features

• Symptoms of anaemia

• Glossitis – beefy, red tongue

• Angular stomatitis

• Reversible increased skin pigmentation

• Peripheral neuropathy: symmetrical numbness and tingling in the feet1

 

Investigations

• Haematinic studies – confirm B12 deficiency

• Peripheral blood film - hypersegmented neutrophils

• Anti-parietal cell and anti-intrinsic factor antibodies

 

Management

• If neurological symptoms present, immediately refer the patient to a haematologist

• If no neurological symptoms present:

  • Cause of B12 deficiency is dietary – advise increase in B12 rich foods, oral cyanocobalamin (can also give IM injections)

  • Cause of B12 deficiency is non-dietary – intramuscular B12 injections hydroxycobalamin1

 

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Folate Deficiency

Causes

1. Inadequate intake

• Folate-rich foods include green leafy vegetables.

 

2. Conditions which require higher levels of folate

• Folate is required in DNA synthesis, so conditions of high cell turnover will use up more folate. Examples include haemolytic anaemia, haematological malignancies, pregnancy, and malignancy.

 

3. Malabsorption

• Folate is absorbed in the duodenum and jejunum. Disease processes that affect this part of the bowel can impair absorption. Examples include tropical sprue and Celiac disease.

 

4. Drugs

• The mechanism of action of some anti-metabolite drugs is through folate antagonism. This includes methotrexate and trimethoprim.

 

Clinical Features

• Symptoms of anaemia or asymptomatic

 

Investigations​

• Haematinic studies (confirm folate deficiency)

• If features of celiac disease, anti-TTG antibodies, duodenal biopsy1

 

Management

Folate deficiency can be treated with oral folic acid supplements. This is given prophylactically in pregnancy to reduce the incidence of neural tube defects, and is given to patients taking methotrexate.

 

References

1. Hoffbrand V, Moss P. Hoffbrand's Essential Haematology. Oxford: John Wiley & Sons, Ltd; 2016.​

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Image courtesy of Dr Francesca Leonforte. 

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