Iron Deficiency Anemia

Aka: Iron Deficiency Anemia, Iron Deficiency

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II. Epidemiology

  1. Most common cause of Microcytic Anemia (50% of cases)
  2. Most common nutritional disorder worldwide
  3. Incidence (U.S.)
    1. Children 1-5 years: 1-2%
      1. Rare before age 6 months in term infants
      2. Rare until birth weight doubles in Preterm Infants
    2. Men: 2-3%
    3. Women (non-pregnant): 12% when menstruating
      1. Drops to 6-9% after Menopause
      2. Incidence is 19-22% if Black or Mexican-American
  4. References
    1. (2002) MMWR Morb Mortal Wkly Rep 51:897-9 [PubMed]

III. Causes

  1. Children
    1. See Pediatric Anemia Causes
  2. Premenopausal women
    1. Menorrhagia: 2 mg/day iron lost
    2. Dietary Iron absorption: 1.5 - 1.8 mg/day iron gained
    3. Each Pregnancy: 500 to 1000 mg iron lost
  3. Males and Postmenopausal women
    1. Colon Cancer until proven otherwise
    2. Gastrointestinal blood Loss
      1. Gastritis from NSAID use
      2. Peptic Ulcer Disease
    3. Partial gastrectomy
    4. Bariatric Surgery (Gastric Bypass)
    5. Diverticulosis
    6. Gastrointestinal Angiodysplasia
    7. Ulcerative Colitis
    8. Celiac Sprue
    9. Increased iron requirements
      1. Pregnancy (see above)
      2. Childhood
  4. Uncommon Causes
    1. Gastrointestinal Parasites (e.g. Hookworms)
    2. Gastrointestinal blood loss in long distance Running
    3. Hereditary Hemorrhagic Telangiectasia
    4. Pulmonary Hemosiderosis

IV. Symptoms and Signs

  1. See Pica
  2. See Anemia Signs
  3. Change in stool color (Melena or bright red blood)
  4. History of excessive menstrual flow (Menorrhagia)
  5. Gastrointestinal condition history or Family History
    1. Gastrointestinal Bleeding (e.g. Peptic Ulcer Disease)
    2. Celiac Sprue
    3. Inflammatory Bowel Disease
    4. Colon cancer Family History
  6. Medication usage predisposing to GI Bleeding
    1. NSAIDs
    2. Aspirin
    3. Corticosteroids

V. Associated Conditions

  1. Generalized Pruritus
  2. Restless Leg Syndrome
  3. Glossitis
  4. Angular Cheilitis
  5. Fatigue
  6. Developmental Delay in children

VI. Labs

  1. Complete Blood Count (CBC)
    1. See Hemoglobin Cutoffs for Anemia
    2. See Hematocrit Cutoffs for Anemia
    3. Mean Corpuscular Volume (MCV)
      1. General
        1. See MCV Cutoffs for Microcytic Anemia
        2. MCV cutoff varies by age and per reference
        3. MCV usually <75 in Iron Deficiency Anemia
        4. MCV >95 fl virtually excludes Iron Deficiency (Test Sensitivity >97%)
      2. Normocytic Anemia (MCV 80 to 100 fl)
        1. Normocytic early in course of Anemia
        2. Normocytic erythrocytes are found in 40% of Iron Deficiency patients
      3. Microcytic Anemia (MCV <80 fl)
        1. Microcytosis follows Hemoglobin drop of 2 g/dl
    4. Red Cell Distribution Width (RDW)
      1. Precedes change in Mean Corpuscular Volume
    5. Mean Corpuscular Volume to Red Blood Cell Count ratio
      1. See Mentzer Index
      2. Ratio <13: Thalassemia
      3. Ratio >13: Iron Deficiency Anemia, Hemoglobinopathy
  2. Iron Studies (in order of sensitivity)
    1. Serum Ferritin <30-45 ng/ml (usually <15-20 ng/ml)
      1. Falls before other indices
      2. Most sensitive for Iron Deficiency Anemia
        1. Serum Ferritin <30ng/ml is 92% sensitive and 98% specific for Iron Deficiency
      3. Falsely elevated as acute phase reactant
        1. Serum Ferritin <50 ng/ml cutoff is used in Iron Deficiency with inflammatory states
        2. Serum Ferritin >100 ng/ml excludes Iron Deficiency despite inflammatory state
    2. Total Iron Binding Capacity (TIBC) rises
    3. Serum Iron
      1. Falls after Serum Ferritin
      2. Falls after Total Iron Binding Capacity (TIBC)
    4. Transferrin Saturation decreased (<5-9%)
      1. Serum Iron to Total Iron Binding Capacity
      2. Falls after Serum Ferritin
    5. Serum Transferrin receptor assay (new)
      1. Increased in Iron Deficiency Anemia
      2. Normal in Anemia of Chronic Disease
  3. Other diagnostic tests (indicated in unclear diagnosis)
    1. Soluble Transferrin Receptor
      1. Indirect measure of Erythropoiesis
      2. Increased in Iron Deficiency
      3. Not affected by inflammatory states
    2. Erythrocyte Protoporphyrin level
      1. Heme precursor
      2. Increased in Iron Deficiency
      3. Similar timing as with Transferrin Saturation
    3. Bone Marrow Biopsy
      1. Indicated when diagnosis is unclear despite above testing
  4. Reticulocyte Count or Reticulocyte Index
    1. Useful in categorization of Anemia type
    2. Does not assess degree of Iron Deficiency Anemia
  5. Images
    1. HemeoncAnemiaIronDeficiency.jpg
    2. HemeoncAnemiaIronDeficiencyOnTreatment.jpg

VII. Differential Diagnosis

  1. See Microcytic Anemia
  2. Thalassemia

VIII. Precautions: Identify a source of blood loss

  1. High correlation to Colon Cancer in older patients
    1. Exercise caution in adult men and postmenopausal women with Iron Deficiency Anemia
    2. Ioannou (2002) Am J Med 113:276-80 [PubMed]

IX. Management

  1. Children
    1. See Pediatric Anemia
  2. Iron Supplementation
    1. Bone Marrow response limited to 20 mg/day iron
    2. Typical adult dosing
      1. See Ferrous Sulfate for administration precautions
        1. Iron absorption reduced up to 40% when taken with meals
        2. Further absorption is reduced with gastric acid hyposecretion (e.g. Proton Pump Inhibitor use)
      2. Elemental iron: 120 mg orally daily
      3. Ferrous Sulfate: 325 mg orally daily
        1. Continue Ferrous Sulfate 325 mg orally daily for at least 3 months
        2. Additional 1-3 months may be required to replenish iron stores
    3. Anticipated response
      1. Hemoglobin increases 1 gram/dl every 2-3 weeks
      2. Iron stores normalize after Hemoglobin is corrected
        1. May require additional 4 months to normalize
      3. Example timeline
        1. Week 2: Reticulocytosis (<10%)
        2. Week 3: Increased Hemoglobin Halfway to normal
        3. Week 8: Normal Hemoglobin
  3. Evaluate failure to respond to Iron Supplementation
    1. Noncompliance
    2. Poor iron absorption due to concurrent medications
      1. Concurrent Antacid use
    3. Continued excessive blood loss
    4. Consider Parenteral Iron if true malabsorption

X. Resources: Patient Education

  1. Information from your Family Doctor: Iron Deficiency
    1. http://www.familydoctor.org/healthfacts/009/

XI. References

  1. Short (2013) Am Fam Physician 87(2):98-104 [PubMed]
  2. (1998) MMWR Morb Mortal Wkly Rep 47:1-29 [PubMed]
    1. http://www.cdc.gov/mmwr/pdf/rr/rr4703.pdf
  3. Shine (1997) Am Fam Physician 55(7): 2455-62 [PubMed]

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