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Key Features

Essentials of Diagnosis

  • Iron deficiency is present if serum ferritin < 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)

  • 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

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 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 deficiency progresses, anisocytosis (variation in red blood cell [RBC] size) and poikilocytosis (variation in RBC shape) develop

  • Abnormal peripheral blood smear, severely hypochromic cells, target cells, pencil-shaped or cigar-shaped cells in severe iron deficiency; platelet count is commonly increased, but it usually remains < 800,000/mcL

  • Bone marrow biopsy for evaluation of iron stores

    • Rarely performed

    • If done, shows the absence of iron in erythroid progenitor cells by Prussian blue staining

  • As the MCV falls (ie, microcytosis), the blood smear shows hypochromic microcytic cells

  • Low hepcidin level in isolated iron deficiency anemia; however, this test is not yet clinically available

Treatment

Medications

  • Ferrous sulfate, 325 mg orally once daily

    • Taken on an empty stomach is standard approach

    • Nausea and constipation limit patient compliance

    • Extended-release ferrous sulfate with mucoprotease ...

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