Is a folic acid deficiency characterized as a microcytic anemia?

Folic Acid Deficiency is NOT a Microcytic Anemia

No, folic acid deficiency does not cause microcytic anemia but rather causes macrocytic megaloblastic anemia. 1, 2, 3

Classification of Anemias by Cell Size

Anemias can be classified based on red blood cell size (MCV):

1. Microcytic anemia (MCV < 80 fL):

   • Iron deficiency anemia
   • Thalassemia
   • Anemia of chronic disease/inflammation
   • Sideroblastic anemia 4

2. Macrocytic anemia (MCV > 100 fL):

   • Megaloblastic anemia due to:
     • Vitamin B12 deficiency
     • Folate (folic acid) deficiency
   • Non-megaloblastic causes:
     • Alcoholism
     • Myelodysplastic syndrome
     • Medication-induced 4

3. Normocytic anemia (MCV 80-100 fL):

   • Hemorrhage
   • Hemolysis
   • Bone marrow failure
   • Anemia of chronic inflammation
   • Renal insufficiency 4

Folic Acid Deficiency Pathophysiology

Folic acid deficiency causes macrocytic megaloblastic anemia through the following mechanism:

• Folic acid is required for nucleoprotein synthesis and normal erythropoiesis 2, 3
• It acts as a precursor to tetrahydrofolic acid, which is a cofactor for transformylation reactions in purine and thymidylate biosynthesis 2, 3
• Deficiency impairs thymidylate synthesis, leading to defective DNA synthesis 2, 3
• This defective DNA synthesis results in megaloblast formation and macrocytic anemia 2, 3

Diagnostic Features of Folic Acid Deficiency

• Macrocytosis in blood and megaloblastosis in bone marrow 5
• Red blood cell folate levels below normal (normal range: 175-316 ng/mL) 2, 3
• Serum folate levels below 5 ng/mL indicate deficiency 2, 3
• Serum folate levels below 2 ng/mL usually result in megaloblastic anemia 2, 3
• Clinical symptoms include:
  • Megaloblastic anemia
  • Pancytopenia
  • Glossitis
  • Angular stomatitis
  • Oral ulcers
  • Neuropsychiatric manifestations (depression, irritability, insomnia, cognitive impairment) 1

Important Clinical Considerations

• Folic acid and vitamin B12 deficiencies present with similar symptoms 1
• Both cause megaloblastic anemia, not microcytic anemia 1, 6
• Patients with folic acid deficiency should also be evaluated for cobalamin (B12) deficiency 1
• Treating folic acid deficiency without addressing concomitant B12 deficiency may improve blood parameters but worsen neurological manifestations 1
• In rare cases, folic acid deficiency patients may have concomitant normocytic (23.7%) or microcytic (11.1%) anemia due to other concurrent conditions 7

Diagnostic Approach

When evaluating anemia:

• Obtain CBC with indices and calculate reticulocyte index 4
• Assess RBC size, shape, and color 4
• For suspected folate deficiency, measure:
  • Serum folate (short-term status)
  • RBC folate (long-term status) 1
  • Homocysteine levels (elevated in both folate and B12 deficiency) 1

Treatment

For confirmed folic acid deficiency:

• Oral administration of 1-5 mg folic acid per day 1
• Treatment should last four months or until the cause of deficiency is corrected 1
• After clinical symptoms subside and blood picture normalizes, maintain with 330 μg DFE daily for adults 1
• If oral treatment is ineffective or not tolerated, folic acid can be given subcutaneously, IV, or IM at 0.1 mg/day 1

Remember that while iron deficiency causes microcytic anemia, folic acid deficiency results in macrocytic megaloblastic anemia, representing opposite ends of the MCV spectrum in anemia classification.