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Megaloblastic Anemia: Overview and Risk Factors

Megaloblastic anemia is characterized by enlarged and oval shaped red blood cells and is frequently caused by vitamin B12 (cobalamin) or folate deficiency. Numerous hematologic and neurologic abnormalities can result from the impaired DNA processes due to inadequate B12 or folate concentrations.

Vitamin B12 deficiency causes subacute combined neurologic degeneration, which can be severe and sometimes irreversible. Neurologic defects may occur with or without anemia. The signs and symptoms include:

  • Paresthesias of the hands and feet.
  • Symmetrical and progressive spastic and ataxic weakness.
  • Loss of deep tendon reflexes.
  • Irritability and mental status changes (megaloblastic madness).

Other symptoms of vitamin B12 or folate deficiency may include fatigue, weakness, glossitis, gastrointestinal problems (eg, diarrhea), decreased appetite, changes in taste, and weight loss. These symptoms sometimes precede anemia. However, megaloblastic anemia is often asymptomatic until the condition is quite severe.

Risk Factors

Vitamin B12 deficiency may result from:

Intrinsic factor deficiency. Intrinsic factor is required for vitamin B12 absorption. A deficiency can occur congenitally or through chronic gastritis, gastrectomy, or autoimmune processes directed at intrinsic factor or the gastric parietal cells that produce it. When anemia results from an intrinsic factor deficiency, it is called pernicious anemia.

Malabsorption. Small bowel and pancreatic disease and alcohol abuse contribute to poor B12 absorption. Elderly persons may also have reduced B12 absorption.

Other gastric disease. Occasionally, individuals with H. pylori gastritis, total or partial gastrectomy, or gastric bypass may develop a B12 deficiency.

Medications. Metformin (reversible with calcium supplements), proton pump inhibitors, H2–blockers, antacids, and antibiotic use (with subsequent bacterial overgrowth) may inhibit B12 absorption.

HIV infection. Weight loss and diarrhea in HIV/AIDS are associated with B12 deficiency.1

Fish tapeworm. Fish tapeworm competes for available B12.

Dietary deficiency. See Nutritional Considerations.

Folate deficiency may result from:

Alcohol abuse. Alcohol interferes with the enterohepatic cycle and absorption of folate.

Malabsorption. Malabsorptive diseases, such as inflammatory bowel disease and sprue, decrease folate absorption.

Pregnancy and breast–feeding. Because fetal and infant growth requires increased folate, pregnancy and breast–feeding may deplete a woman’s folate stores. In turn, an exclusively breast–fed infant whose mother is folate–deficient will not receive adequate folate.

Medications. Intake of certain medications, such as methotrexate, phenytoin, and trimethoprim, may lead to folate deficiency.

Hemolysis and exfoliative dermatitis. Both conditions increase the demand for folate.

Vitamin B12 deficiency. Because Vitamin B12 is responsible for the formation of the metabolically active form of folic acid, its deficiency can lead to folate deficiency.

Dietary deficiency. See Nutritional Considerations.


Megaloblastic Anemia: Diagnosis and Treatment >>