Macrocytic (megaloblastic) anaemia is a disorder characterized by enlarged red blood cells (high Mean Corpuscular Volume – MCV) due to impaired DNA synthesis during erythropoiesis.

The most common causes are:

• Vitamin B12 deficiency

• Folate deficiency

Folate deficiency commonly occurs in pregnancy and postpartum states, while vitamin B12 deficiency typically affects middle-aged and elderly adults and may result in irreversible neurological damage if untreated.

Outside pregnancy, macrocytic anaemia always requires investigation to determine the underlying cause.

2. Pathophysiology

Vitamin B12 and folate are essential for DNA synthesis.

Deficiency leads to:

1. Impaired thymidine production

2. Failure of nuclear maturation

3. Continued cytoplasmic growth

4. Formation of large immature erythrocytes (megaloblasts)

In Vitamin B12 deficiency additionally:

• Myelin degeneration occurs

• Peripheral neuropathy develops

• Spinal cord demyelination (subacute combined degeneration)

3. Causes

A. Vitamin B12 Deficiency

B. Folate Deficiency

4. Risk Factors

• Elderly age

• Vegetarian/vegan diet

• Alcohol use disorder

• Pregnancy/postpartum

• Chronic gastrointestinal disease

• HIV and TB

• Long-term metformin therapy

• Gastric surgery

5. Signs and Symptoms

General Anaemia Features

• Fatigue

• Pallor

• Shortness of breath

• Dizziness

• Palpitations

Features Suggesting Vitamin B12 Deficiency

(Neurological — key differentiator)

• Numbness and tingling in hands/feet

• Loss of vibration and position sense

• Gait disturbance

• Memory impairment

• Depression

• Confusion

• Peripheral neuropathy

• Spasticity (late stage)

Features Suggesting Folate Deficiency

• Glossitis

• Mouth ulcers

• No neurological symptoms

6. Diagnostic Criteria

7. Investigations

Laboratory Tests

Additional Tests

• Bone marrow biopsy (rare cases)

• Thyroid function tests

• Liver function tests

• Stool for parasites

8. Management

Treatment Principles

1. Identify cause

2. Replace deficiency

3. Prevent neurological damage

4. Monitor response

A. Non-Pharmacological Management

Dietary Advice

Increase folate-rich foods:

• Liver

• Eggs

• Citrus fruits

• Spinach and green vegetables

• Lentils, beans, peanuts

• Fortified cereals

Increase vitamin B12 foods:

• Meat (especially liver)

• Fish

• Dairy products

• Eggs

Additional advice:

• Reduce alcohol intake

• High-protein diet: 1.5 g/kg/day

B. Pharmacological Treatment

1. Folate Deficiency

• Folic acid 5 mg orally daily

• Continue until haemoglobin normalizes

• Check Hb monthly

Never give folate alone if B12 deficiency is suspected — it can worsen neurological damage.

2. Vitamin B12 Deficiency

Initial Therapy

• Hydroxocobalamin 1 mg IM daily for 1 week

• Then weekly for 4 weeks

Maintenance

• 1 mg IM every 2–3 months (lifelong in pernicious anaemia)

9. Monitoring Response

10. Complications

• Permanent neuropathy

• Spinal cord degeneration

• Dementia

• Heart failure (severe anaemia)

• Pancytopenia

11. Prevention

• Balanced diet including animal products

• Supplementation in pregnancy

• Screening elderly patients

• Treat malabsorption disorders early

12. Prognosis