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Hematology & Blood Transfusion

Megaloblastic Anaemia

A type of macrocytic anaemia characterized by the presence of large, immature red blood cell precursors (megaloblasts) in the bone marrow, usually due to impaired DNA synthesis caused by Vitamin B12 (cobalamin) or Folate (folic acid) deficiency.

Also known as: Vitamin B12 Deficiency Anaemia, Folate Deficiency Anaemia, Macrocytic Anaemia

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Referral and warning signs

When to refer

Refer to specialist for: Diagnostic uncertainty, Suspected pernicious anaemia/malabsorption, Significant neurological symptoms, Failure to respond, Need for further investigation.

Red flags

  • Significant neurological symptoms
  • Pancytopenia
  • Severe anaemia requiring transfusion
  • Suspicion of underlying malignancy

Signs and symptoms

  • General symptoms of anaemia (fatigue, pallor, dyspnoea, dizziness).
  • Symptoms related to underlying deficiency:
  • - Glossitis (sore, smooth, beefy-red tongue) - common in both.
  • - Mild jaundice (due to ineffective erythropoiesis).
  • - Vitamin B12 Deficiency Specific: Neurological symptoms - peripheral neuropathy (symmetrical paraesthesias in feet/hands, numbness, tingling), impaired proprioception/vibration sense, gait ataxia, weakness, memory loss, dementia, depression, psychosis (Subacute Combined Degeneration of the Cord). Neurological damage can be irreversible if treatment delayed.
  • - Folate Deficiency Specific: Usually NO neurological symptoms (apart from general anaemia effects).
  • Diarrhoea, anorexia, weight loss may occur.

Risk factors

  • Folate Deficiency: Inadequate Dietary Intake (leafy greens, fruits, fortified cereals), Malabsorption (celiac, Crohn's), Increased Requirements (pregnancy, haemolysis, malignancy), Medications (Methotrexate, Trimethoprim, Phenytoin), Alcoholism.
  • Vitamin B12 Deficiency: Pernicious Anaemia (autoimmune gastritis), Inadequate Dietary Intake (strict vegans), Malabsorption (gastric/ileal surgery/disease, bacterial overgrowth, tapeworm), Medications (Metformin, PPIs).

Diagnosis

Clinical assessment

Suspect based on macrocytic anaemia (high MCV) +/- glossitis +/- neurological symptoms (suggestive of B12 deficiency). Assess diet, alcohol, medications, GI symptoms, neuro exam.

Investigations

  • Complete Blood Count (CBC): Low Hb, High MCV (>100 fL), High MCH. Pancytopenia possible.
  • Peripheral Blood Smear: Oval macrocytes, hypersegmented neutrophils (≥6 lobes).
  • Serum Vitamin B12 Level: Low confirms B12 deficiency.
  • Serum Folate Level: Low confirms folate deficiency (Red Cell Folate reflects longer stores).
  • Tests for Cause of B12 Deficiency: Anti-Intrinsic Factor/Parietal Cell Antibodies (pernicious anaemia), Endoscopy.
  • Homocysteine and Methylmalonic Acid (MMA): Both elevated in B12 deficiency (MMA normal in folate).
  • Bone Marrow Examination (rarely needed): Megaloblastic changes.

Diagnostic criteria

Macrocytic anaemia with low serum Vitamin B12 or Folate levels. Peripheral smear findings supportive.

Management

Non-pharmacological management

  • Identify and treat underlying cause.
  • Dietary counseling (folate-rich foods, B12-rich foods/supplements for vegans).

Pharmacological treatment

  • Vitamin B12 Deficiency: Parenteral Replacement (Hydroxocobalamin 1mg IM daily loading, then weekly, then every 2-3 months lifelong if irreversible) OR High-dose Oral B12 (1-2mg daily).
  • Folate Deficiency: Oral Folic Acid 5mg daily for 1-4 months. Crucial: Rule out/treat concurrent B12 deficiency FIRST to avoid worsening neuro damage.
  • Combined Deficiency: Treat both.
  • Iron supplementation if co-deficient.

Monitoring

Monitor CBC and reticulocyte count (expect rise early). Monitor MCV. Monitor B12/Folate levels if needed. Monitor neurological symptoms (B12).

Complications

  • Severe anaemia / Heart failure
  • Permanent neurological damage (B12 deficiency)
  • Infertility
  • Increased gastric cancer risk (Pernicious Anaemia)
  • Neural tube defects in offspring (maternal folate deficiency)

Prevention

  • Adequate dietary intake.
  • Folic acid supplementation before/during pregnancy.
  • B12 supplementation for vegans.
  • Monitoring/supplementation after gastric/ileal surgery.

Patient education

  • Explain cause (B12/Folate deficiency).
  • Importance of replacement (injections/oral).
  • Lifelong B12 need if irreversible cause.
  • Dietary advice.
  • Neurological risks of untreated B12.
  • Importance of follow-up.

Uganda-specific notes

Folate deficiency common (diet, malaria/haemolysis). B12 deficiency less common but occurs. Check B12 before giving folate alone.

References

  • Uganda Clinical Guidelines (UCG) 2023

    Chapter 11, Section 11.1.1.2

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