II. Epidemiology

  1. Most common cause of Microcytic Anemia (50% of cases)
  2. Most common nutritional disorder worldwide
  3. Incidence
    1. Children: 4-7% under age 15 years
      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

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

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

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/

Images: Related links to external sites (from Google)

Ontology: Iron deficiency anemia (C0162316)

Definition (NCI) Anemia caused by low iron intake, inefficient iron absorption in the gastrointestinal tract, or chronic blood loss.
Definition (MSH) Anemia characterized by decreased or absent iron stores, low serum iron concentration, low transferrin saturation, and low hemoglobin concentration or hematocrit value. The erythrocytes are hypochromic and microcytic and the iron binding capacity is increased.
Concepts Disease or Syndrome (T047)
MSH D018798
ICD9 280.9, 280
ICD10 D50 , D50.9
SnomedCT 234354003, 191133000, 191137004, 87522002, 154787005, 191126000, 267553005, 191125001
English Anemias, Iron Deficiency, Iron deficiency anemias, ANEMIA IRON DEFICIENCY, ANAEMIA IRON DEFICIENCY, ANEMIA, IRON DEFICIENCY, Anemia, Iron-Deficiency, Anemias, Iron-Deficiency, IRON DEFICIENCY ANEMIA, Iron Deficiency Anemias, Iron-Deficiency Anemia, Iron-Deficiency Anemias, Iron deficiency anemia, NOS, Iron deficiency anemia, unspecified, Iron def anaemia syndrome, Iron def anemia syndrome, Iron deficiency anaemia NOS, Iron deficiency anaemia, NOS, Iron deficiency anaemia, unspecified, Iron deficiency anemia NOS, Iron def anemia, Unspec iron deficiency anaemia, Unspec iron deficiency anemia, Unspecified iron deficiency anaemia, Unspecified iron deficiency anemia, ANEMIA IRON DEFIC, IRON DEFIC ANEMIAS, IRON DEFIC ANEMIA, ANEMIAS IRON DEFIC, ferropenic anemia, sideropenic anemia, iron deficiency anemia, iron deficiency anemia (diagnosis), fe deficiency anemia, fe defxy anemia, Iron deficiency anaemia syndrome (disorder), iron deficiency, Iron Deficiency Anemia, Iron def anaemia, Anaemia iron deficiency, Iron deficiency anaemias, Anemia iron deficiency, ANEMIA DEFICIENCY IRON, Iron defic anemia NOS, Unspecified iron deficiency anemia (disorder), Iron deficiency anemia NOS (disorder), Anemia, Iron-Deficiency [Disease/Finding], hypoferric anemia, Anaemia;iron deficiency, iron-deficiency anemia, Anemia, Iron Deficiency, Sideropenic anemia, Iron deficiency anaemia, Iron deficiency anaemia syndrome, Iron deficiency anemia syndrome, Sideropenic anaemia, IDA - Iron deficiency anaemia, IDA - Iron deficiency anemia, Iron deficiency anemia (disorder), Iron deficiency anemia, deficiency; anemia, iron, iron deficiency anaemia, iron deficiency; anemia, iron; deficiency, anemia, sideropenic; anemia, anemia; deficiency, iron, anemia; iron deficiency, anemia; sideropenic, Anaemia - iron defic., Anemia - iron defic., Fe deficiency anemia NOS, Anemia;iron deficiency
Dutch ijzerdeficiëntieanemieën, ijzergebrekanemie, niet-gespecificeerd, sideropenische anemie, ijzerdeficiëntieanemia, ijzerdeficiëntieanemie, niet-gespecificeerd, IJzergebrekanemie, anemie; deficiëntie, ijzer, anemie; ijzerdeficiëntie, anemie; sideropenisch, deficiëntie; anemie, ijzer, ferriprief; anemie, ijzer; deficiëntie, anemie, sideropenisch; anemie, IJzergebreksanemie, niet gespecificeerd, ijzerdeficiëntieanemie, IJzergebreksanemie, Anemie, ijzergebreks-
French Anémie due à une carence en fer, Anémie par déf fer, Anémies ferriprives, Anémie par carence en fer, non précisée, Anémie ferriprive non précisée, ANEMIE PAR DEFICIENCE MARTIALE, Anemie par carence en fer, Anémie sidéropénique, Anémie ferriprive, Anémie par carence en fer, Anémie hypochrome ferriprive, Anémie par carence martiale
German sideropenische Anaemie, Eisenmangelanaemie, unspezifisch, Eisenmangelanaemien, EISENMANGELANAEMIE, Eisenmangelanaemie, nicht naeher bezeichnet, Eisenmangelanaemie, Anämie, Eisenmangel-, Eisenmangelanämie
Italian Anemia da carenza di ferro, Anemia sideropenica, non specificata, Anemie da carenza di ferro, Anemia da carenza di ferro, non specificata, Anemie ferroprive, Anemie sideropeniche, Anemia ferropriva, Anemia sideropenica
Portuguese Anemias por carência de ferro, Anemia por carência de ferro NE, Anemia sideropénica, ANEMIA POR DEFICIENCIA EM FERRO, Anemia por deficiencia de ferro, Anemia por carência de ferro, Anemia Ferropriva, Anemia por Deficiência de Ferro
Spanish Anemia por déficit de hierro, Anemia por deficiencia de hierro, no especificada, Anemia por déficit de hierro no especificada, Anemia sideropénica, Anemia ferropriva, Anemias por déficit de hierro, Anemia - iron defic., Sideropenic anemia, Anaemia - iron defic., Iron deficiency anemias, Iron deficiency anemia, Iron deficiency anaemia syndrome, Iron deficiency anaemia, Iron deficiency anaemias, Sideropenic anaemia, Iron deficiency anemia syndrome, ANEMIA FERROPENICA, Anemia ferropénica, Anemia ferropenica, anemia ferropénica (trastorno), anemia ferropénica no especificada (trastorno), anemia ferropénica no especificada, anemia ferropénica, SAI (trastorno), anemia ferropénica, SAI, anemia ferropénica, anemia por deficiencia de hierro, SAI, anemia por deficiencia de hierro, anemia por déficit de hierro no especificada, anemia por déficit de hierro, SAI, anemia sideropénica, Anemia Ferropénica, Anemia Ferropenica
Japanese 詳細不明の鉄欠乏性貧血, テツケツボウセイヒンケツ, ショウサイフメイノテツケツボウセイヒンケツ, 鉄欠乏性貧血, 貧血-鉄欠乏性
Swedish Järnbristanemi, JARNBRISTANEMI
Czech anémie z nedostatku železa, Různé anémie z deficitu železa, Sideropenická anémie blíže neurčená, Anémie z nedostatku železa, Různé anémie z nedostatku železa, Sideropenická anémie, Anémie z deficitu železa
Finnish Raudanpuuteanemia, RAUDANPUUTEANEMIA
Russian ANEMIIA SIDEROPENICHESKAIA, ZHELEZODEFITSITNAIA ANEMIIA, ANEMIIA ZHELEZODEFITSITNAIA, АНЕМИЯ ЖЕЛЕЗОДЕФИЦИТНАЯ, АНЕМИЯ СИДЕРОПЕНИЧЕСКАЯ, ЖЕЛЕЗОДЕФИЦИТНАЯ АНЕМИЯ
Norwegian JERNMANGEL ANEMI
Danish Jernmangel-anaemi
Hungarian vashianyos anaemia, Vashiányos vérszegénység, anaemia siderpenica, Vas hiány anémia, vashiányos anémia, Vashiányos anaemia, Vas hiány anaemia, Vashiányos anaemia, nem meghatározott, vashiányos anaemia, nem meghatározott, Vashiányos anaemiák, Siderpeniás anaemia
Korean 상세불명의 철결핍성 빈혈, 철결핍성 빈혈
Croatian ANEMIJA, SIDEROPENIČNA
Basque ANEMIA FERRIPRIBOA
Hebrew anemia mixoser barzel
Polish Niedokrwistość z niedoboru żelaza