Megaloblastic Anaemia

Clinical Description

• Anaemia characterized by formation of unusually large, abnormal and immature red blood cells, called megaloblasts. It is caused by a deficiency of folate and/or vitamin B12.
• Causes of vitamin B12 deficiency; poor diet intake (e.g., vegan), diseases affecting

Vitamin B12 absorption in the gut e.g., pernicious anaemia, fish tapeworm, gastrectomy, ileum resection, Crohn’s disease, celiac disease.

• Causes of folic acid deficiency; diet low in fresh fruits/vegetables/fortified cereals, diseases affecting folic acid absorption in the gut (e.g., Crohn’s disease, celiac disease, excessive alcohol intake), drugs (phenytoin, cotrimoxazole, methotrexate, sulfasalazine).

Signs and Symptoms

• Fatigue, general body weakness, lethargy, dizziness, palpitation, shortness of breath
• Numbness/burning sensation
• Mood changes/psychosis (vitamin B12 deficiency)
• Pallor
• Red beefy tongue, hyperpigmented skin (vitamin B12 deficiency)
• Cerebellar ataxia
• hemiplegia
• Decreased vibration and discriminative touch sensation
• Folate Deficiency
• Glossitis
• Neurotube defects (spina bifida) in neonates

Investigations

• FBC: Elevated MCV (mean corpuscular volume) and MCH (mean corpuscular hemoglobin).
• Macro-ovalocytes on blood smear; poly-segmentation of neutrophils (hyper segmented neutrophils), thrombocytopenia with giant platelets.
• Decreased serum vitamin B12 or red blood cell folate. Pancytopenia in severe cases.
• Intrinsic factor antibodies and anti-parietal cell antibodies in vitamin B 12 deficiency due to pernicious anaemia.

Treatment

Treatment objectives

• Dietary modifications to ensure adequate intake of folate and Vitamin B12.
• Identify and treat the underlying cause, e.g., antibiotics for intestinal overgrowth with bacteria.

Non-pharmacological

Dietary modification:

• Include foods high in folic acid e.g., green leafy vegetables, broccoli, peas, chickpeas, kidney beans liver, breakfast cereals fortified with folic acid.
• Foods high in Vitamin B12: Meat, Fish, Milk, Cheese, Eggs, fortified breakfast cereals.

Pharmacological

• Start with Folic Acid and Vitamin B12. Take blood samples for RBC, folate and vitamin B12 levels before starting treatment.
• Monitor serum potassium and replace if necessary.
• Give vitamin B12 and folic acid together until the test results are available as giving folic acid alone in patients with a B12 deficiency may precipitate a permanent neurological deficit.
• Adjust management according to results.
• Folic acid deficiency:
• Folic acid, oral, 5 q24h until hemoglobin returns to normal.
• Prolonged treatment may be required for malabsorption states.
• Vitamin B12 deficiency:
• Vitamin B12, IM. 1 mg daily for 7 days, then weekly for a further 4 doses.
• Follow with 1 mg every third month for life in patients with pernicious anaemia, except in patients with clearly modifiable nutritional deficiency.
• The anemia is corrected within 1-2 months. As there is an increase in red blood cell production, short-term iron and folic acid supplementation is also recommended.
• Consider the following if there is failure to respond: co-existing folate and/or iron deficiency, infection, hypothyroidism, myelodysplasia, incorrect diagnosis, and drug-induced, e.g., hydroxyurea and Zidovudine.
• Prophylaxis. Vitamin B12 is indicated for patients after total gastrectomy or ileal resection. Give vitamin B12, IM, 1 mg every third month for life (4 times a year).
• Indications for prophylactic folic acid: chronic inherited haemolytic anemia, sickle cell anaemia, thalassemia; myeloproliferative disorders; exfoliative skin disorders; increased demands, e.g. pregnancy, chronic hemodialysis. Give Folic acid, oral, 5mg q24h