Anemia, Iron Deficiency

KEY FEATURES

Essentials of Diagnosis

• Iron deficiency is present if serum ferritin is < 12 ng/mL or < 30 ng/mL if also anemic

• In adults, caused by bleeding unless proved otherwise

• Responds to iron therapy

General Considerations

• Most common cause of anemia worldwide

• Causes

  • Blood loss (gastrointestinal [GI], menstrual, repeated blood donation)

  • Deficient diet

  • Decreased absorption of iron

  • Increased requirements (pregnancy, lactation)

  • Celiac disease (gluten enteropathy)

  • Hemoglobinuria

  • Iron sequestration (pulmonary hemosiderosis)

• With hemorrhage decreased oxygen to kidneys stabilizes hypoxia-inducible factor and increases erythropoietin in kidneys and liver; this stimulates synthesis of erythroferrone, which suppresses hepcidin synthesis; this leads to ferroportin stability and enhanced iron transport across GI lumen.

• Women with heavy menstrual losses may require more iron than can reasonably be absorbed; thus, they often become iron deficient

• Pregnancy and lactation also increase requirement for iron, necessitating medicinal iron supplementation

• Long-term aspirin use may cause blood loss even without documented structural lesion

• Search for a source of GI bleeding if other sites of blood loss (menorrhagia, other uterine bleeding, and repeated blood donations) are excluded

• Hereditary iron-refractory iron deficiency anemia

  • Rare autosomal recessive disorder

  • Defined as hemoglobin increment of < 1 g/dL (10 g/L) after 4–6 weeks of 100 mg/d of elemental oral iron

Demographics

• More common in women as a result of menstrual losses

CLINICAL FINDINGS

Symptoms and Signs

• Symptoms of anemia (eg, easy fatigability, dyspnea, palpitations and tachypnea on exertion)

• Skin and mucosal changes (eg, smooth tongue, brittle nails, spooning of nails [koilonychia], and cheilosis) in severe iron deficiency

• Dysphagia resulting from esophageal webs (Plummer-Vinson syndrome) may occur in severe iron deficiency

• Pica (ie, craving for specific foods [eg, ice chips, lettuce] often not rich in iron) is frequent

Differential Diagnosis

• Microcytic anemia resulting from other causes

  • Thalassemia

  • Anemia of chronic disease

  • Sideroblastic anemia

  • Lead poisoning

  • Zinc deficiency

DIAGNOSIS

Laboratory Tests

• Diagnosis can be made by

  • Laboratory confirmation of an iron-deficient state

  • Evaluation of response to a therapeutic trial of iron replacement

• The reticulocyte count is low or inappropriately normal

• A serum ferritin value < 12 mcg/L is a highly reliable indicator of reduced iron stores

• However, because serum ferritin levels may rise in response to inflammation or other stimuli, a normal ferritin level does not exclude a diagnosis of iron deficiency

• A ferritin level of < 30 ng/mL almost always indicates iron deficiency in anyone who is anemic

• As iron deficiency progresses, serum iron values decline to < 30 mcg/dL and transferrin levels rise to compensate, leading to transferrin saturations of < 15%

• As the MCV falls (ie, microcytosis), the blood ...