Diagnosis and management of iron deficiency anemia in the 21st century

Abstract

Iron deficiency is the single most prevalent nutritional deficiency worldwide. It accounts for anemia in 5% of American women and 2% of American men. The goal of this review article is to assist practitioners in understanding the physiology of iron metabolism and to aid in accurately diagnosing iron deficiency anemia. The current first line of therapy for patients with iron deficiency anemia is oral iron supplementation. Oral supplementation is cheap, safe, and effective at correcting iron deficiency anemia; however, it is not tolerated by some patients and in a subset of patients it is insufficient. Patients in whom the gastrointestinal blood loss exceeds the intestinal ability to absorb iron (e.g. intestinal angiodysplasia) may develop iron deficiency anemia refractory to oral iron supplementation. This population of patients proves to be the most challenging to manage. Historically, these patients have required numerous and frequent blood transfusions and suffer end-organ damage resultant from their refractory anemia. Intravenous iron supplementation fell out of favor secondary to the presence of infrequent but serious side effects. Newer and safer intravenous iron preparations are now available and are likely currently underutilized. This article discusses the possible use of intravenous iron supplementation in the management of patients with severe iron deficiency anemia and those who have failed oral iron supplementation.

Keywords: anemia; blood loss; intravenous iron; iron deficiency; therapy.

Figure 1.

The role of hepcidin in normal iron homeostasis: an increase in plasma iron causes an increase in hepcidin production (yellow arrow). Elevated hepcidin inhibits iron flow into the plasma from the macrophages, hepatocytes, and the duodenum. As the plasma iron continues to be consumed for hemoglobin synthesis, the plasma iron levels decrease and hepcidin production abates, completing the homeostatic loop. (Reprinted with permission from Intrinsic LifeSciences LLC, La Jolla, CA, USA: http://www.intrinsiclifesciences.com/iron_reg/).

Figure 2.

Response of the bone marrow in relation to the level of serum iron. The marrow response is directly associated to the serum iron level (based on a hematocrit level of 25–27%). A is the response of the bone marrow to the body’s physiological increase in iron absorption from the gut in response to iron deficiency. A mean serum iron level <12.5 µmol/l is associated with an increase in RBC production, which ranges from 2.5 to 3.5 times the normal marrow response. B indicates a serum iron level of 12.5–26.8 µmol/l can be achieved with oral iron supplementation (i.e. 300 mg of ferrous gluconate every 2 h while awake), which is associated with an increase in bone marrow production of RBCs 4–5 times normal. C indicates a serum iron level >35.8 µmol/l was achieved by administration of intravenous iron dextran or nonviable red cells. This resulted in an increase in RBC production 4.5–7.8 times the normal marrow response. RBC, red blood cell.