Macrocytic Anaemia

This is an anaemia with MCV > 100um3, most commonly due to folate or Vitamin B12 deficiency.
– These are needed to make DNA which is needed for cell division.

Causes of macrocytic anaemia can be remembered by the acronym FAT RBC MC:

Foetus

Alcohol excess

Thyroid (hypothyroid)

Reticulocytosis (due to haemolytic anaemia as RBC precursors are bigger)

B12/folate deficiency

Cirrhosis (liver)

Myeloproliferative disorders –> precursors are bigger than RBC so increase average volume

Cytotoxic drugs (e.g. 5-fluorouracil)

Folate deficiency

This is found in green leafy vegetables, nuts and liver and is absorbed in the jejunum.

– The deficiency leads to an inability to synthesise enough DNA which leads to megaloblastic anaemia.

Causes:

– Supply –> poor diet seen in elderly + alcoholics

– Increased demand –> pregnancy + cancer

– Malabsorption –> coeliac disease giving small bowel inflammation

– Antifolate drugs –> Methotrexate + Sulfonamide antibiotics

Symptoms:

– Anaemia symptoms –> fatigue, weakness, light headedness etc.

– Glossitis + Angular cheilosis (not koilonychia)

Tests:

– Blood film –> shows hypersegmented neutrophils (>5 lobes)

– Low folate + High homocysteine (as it is not converted to methionine) + Low methylmalonic acid

– Check serum B12 –>  Then do bone marrow biopsy if cause is not revealed by above tests

Management:

1st exclude Vitamin B12 deficiency. Then give folate replacement

Vitamin B12 deficiency

This is common, occurring usually in elderly people – but less common than folate deficiency.

– It takes years to develop unlike folate deficiency due to large hepatic stores of Vitamin B12

Causes:

– Supply –> Vegans do not consume Vitamin B12 as it is only found in animal products

– Malabsorption –> Crohn’s disease and tapeworms affect terminal ileum where it is absorbed

– Pernicious anaemia (most common) –> autoimmune destruction of parietal cells in stomach which produce intrinsic factor

Symptoms:

– Anaemia symptoms –> fatigue, weakness, light headedness + Glossitis + Angular cheilosis

– Lemon tinge to skin due to pallor and mild jaundice (haemolysis)

Tests:

Same as folate deficiency, except there is raised methylmalonic acid

Management:

– B12 3 times/week for 2 weeks, then once/3months by IM injection

If also folic acid deficient, treat Vitamin B12 first to avoid precipitating spinal cord degeneration.

N.B. In addition to anaemia, Vitamin B12 acts as a cofactor to turn methylmalonic acid to succinyl CoA.

In deficiency, methylmalonic acid builds up demyelinating the spinal cord giving neurological symptoms.

 

Subacute combined degeneration of the spinal cord

This is a complication of Vitamin B12 deficiency

– In deficiency, methylmalonic acid builds up demyelinating the spinal cord giving neurological symptoms.

Symptoms:

– Mix of peripheral sensory neuropathy + Upper and lower motor neuron signs

– Gives absent knee jerks and ankle jerks but hyperreflexia of extensors.

– Can also give neuropsychiatric symptoms (mood changes) and ataxia

Sources

Image 1: Paul Weisz Carrington, M.D., Public domain, via Wikimedia Commons

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