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A 43-year-old woman presents with complaints of increasing fatigue, exercise intolerance, and difficulty swallowing. She also reports palpitations and shortness of breath when climbing stairs. She has a past history of fibromyalgia for more than a decade, managed with liberal doses of aspirin and nonsteroidal preparations. She also reports prolonged and irregular menstrual periods for the last 6 months. Examination is notable for pallor of the conjunctiva and mucous membranes; a beefy, red, smooth tongue; and flattened nails. She has considerable tenderness to palpation of the muscles of the neck and shoulders and restricted motion of both shoulders.

CBC: Hematocrit/hemoglobin - 21%/6 g/dL

MCV - 67 fL MCH - 24 pg/cell MCHC - 28 g/dL

Reticulocyte count/index - 3.0%/<1

White blood cell count - Normal

Platelet count - 720,000/μL

Sedimentation rate - 42 mm/h

(Westergren) Stool hemoccult - Brown stool/4+ heme positive



  • How should this anemia be described?

  • What is the differential diagnosis?

  • What other tests should be ordered?

Iron deficiency is a leading cause of microcytic anemia in children and adults. When iron supply to the erythroid marrow is deficient, red blood cell production is impaired and new cells released into circulation are poorly hemoglobinized. The severity of the anemia and the degree of microcytosis and hypochromia generally reflect the severity and chronicity of the iron-deficiency state.

The prevalence of iron deficiency in a population depends on the interaction of several factors, including the adequacy of dietary iron supply and the incidence of disease states, which are accompanied by malabsorption or chronic blood loss. In developing countries, inadequate nutrition is a major factor and iron deficiency is the principal cause of nutritional anemia. In Europe and the United States, by contrast, chronic blood loss is more frequently responsible for an iron-deficiency anemia.


Iron is an essential component in the synthesis of hemoglobin, myoglobin, and several heme and metalloflavoprotein enzymes. It also plays a direct role in governing erythropoiesis by influencing the cell cycle of proliferating red blood cell precursors. A fall in iron supply to the marrow is associated with a fall in cyclin D1 protein and an arrest of erythroid precursors in the G1/S phase, thereby decreasing the proliferative response to erythropoietin.

Iron Loss

Iron is highly conserved in humans. Still, enough is lost to require absorption of between 1 and 4 mg of elemental iron from the diet each day to maintain normal iron balance. The intestine responds to negative iron balance by increasing the efficiency of transport. At the same time, the intestine can virtually shut off transport once stores of iron exceed metabolic requirements.

Iron Transport

Once absorbed, iron binds to a specific plasma protein, transferrin, which transports it to tissues (Figure 5-1...

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