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Source: Cook K, Ineck BA, Lyond WL. Anemias. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th ed. http://www.accesspharmacy.com/content.aspx?aid=7999561. Accessed June 12, 2012.

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  • Decreased oxygen-carrying capacity of blood characterized by a decrease in hemoglobin (Hb) or red blood cells (RBCs)
  • World Health Organization (WHO) definition
    • Men: Hb <13 g/dL (<130 g/L; <8.07 mmol/L)
    • Women: Hb <12 g/dL (<120 g/L; <7.45 mmol/L)

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  • Major causes of folic acid deficiency
    • Inadequate dietary intake
    • Decreased absorption
      • Alcoholics
    • Increased requirements
      • Pregnancy
      • Hemolytic anemia
      • Malignancy
      • Myelofibrosis
      • Chronic inflammatory disorders
      • Long-term dialysis
      • Growth spurts
    • Drugs
      • Folate antagonists (e.g., methotrexate)
      • Reduced folate absorption (e.g., phenytoin)
        • Routine folic acid supplementation generally not recommended

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  • Macrocytic, megaloblastic anemia
  • Folic acid is water-soluble vitamin.
    • Readily destroyed by cooking
    • Obtained through diet
    • Minimum daily requirement: 50 to 100 mcg
      • Increased requirements in pregnant/lactating women
  • Body stores 5 to 10 mg, primarily in liver.
  • Folate distributed to other body tissues via enterohepatic recirculation.

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  • One of the most common vitamin deficiencies due to association with excessive alcohol intake and pregnancy.

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  • Supplementation of folic acid needed to prevent neural tube defects.

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  • Excessive alcohol intake
  • Pregnancy

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  • Patients may be asymptomatic or have vague complaints.

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Signs and Symptoms

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  • Fatigue
  • Dizziness
  • Irritability
  • Symptoms of heart failure
  • Vertigo
  • Faintness
  • Sensitivity to cold
  • Pallor
  • Loss of skin tone
  • Decreased mental acuity

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Means of Confirmation and Diagnosis

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  • Diagnosis is made based on laboratory test results.

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Laboratory Tests

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  • CBC
  • Reticulocyte count
  • RBC folate concentration
    • <150 ng/mL (<340 nmol/L)
    • Better indicator of folic acid deficiency anemia than decreased serum folate concentrations
  • Serum homocysteine
  • Figure 1 shows broad, general algorithm for diagnosis of anemia based on laboratory data.

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Figure 1.
Graphic Jump Location

General algorithm for diagnosis of anemias. (↑, increased; ↓ , decreased; A2, hemoglobin A2; F, hemoglobin F; IF, intrinsic factor; MCV, mean corpuscular volume; Pb, lead; TIBC, total iron-binding capacity; WBC, white blood cells.) Reprinted with permission from Wells BG, DiPiro JT, Schwinghammer TL, et al. Pharmacotherapy Handbook 8th ed. New York: McGraw-Hill, 2012.

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Diagnostic Procedure

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  • Bone marrow aspirate

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Differential Diagnosis

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  • Vitamin B12 deficiency (another cause of megaloblastic anemia)
  • Myelodysplastic syndrome (another cause of macrocytic anemia)

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  • Reverse hematologic manifestations.
  • Replace body stores.
  • Prevent recurrence.

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  • Folic acid 1 mg by mouth daily for 4 months if underlying cause is identified
  • Deficiency due to malabsorption: 1–5 mg by mouth daily
  • Encourage dietary supplementation.

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  • Reticulocyte count—Reticulocytosis begins in first week.
  • CBC—Hct normalizes within 2 months

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  • Rapid improvement in sense of well being

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