Megaloblastic Anemia
Megaloblastic anemia is characterized by impaired DNA synthesis resulting in nuclear-cytoplasmic asynchrony, leading to large, immature, dysfunctional cells (megaloblasts) in the bone marrow.
1. Pathophysiology
The core defect is a deficiency in Vitamin B12 (Cobalamin) or Folic Acid (Vitamin B9), both of which are essential cofactors for DNA synthesis (purine and thymidylate synthesis).
2. Key Distinguishing Features
| Feature | Vitamin B12 Deficiency | Folic Acid Deficiency |
|---|---|---|
| Neurological Symptoms | Present (Subacute Combined Degeneration) | Absent |
| Methylmalonic Acid | Elevated | Normal |
| Homocysteine | Elevated | Elevated |
3. Clinical Pearls
- Peripheral Smear: Macrocytic anemia (MCV > 100 fL) with hypersegmented neutrophils (>5 lobes).
- B12 Causes: Pernicious anemia, vegan diet, malabsorption (Crohn’s, ileal resection), Diphyllobothrium latum infection.
- Folate Causes: Poor diet (alcoholism), pregnancy, drugs (methotrexate, phenytoin).
NEET PG Hint: Never treat B12 deficiency with Folic Acid alone, as it may correct the anemia but will not stop the progression of neurological damage. Always investigate B12 status before starting long-term folate therapy. For a deep dive into hematology and relevant practice questions, visit mymedschool.org.