Iron Deficiency Anemia

Iron is distributed in active metabolic and storage pools. Total body iron is about 3.5 g in healthy men and 2.5 g in women; the difference relates to women's smaller body size and dearth of stored iron because of iron loss due to menses. The distribution of body iron is

• Hemoglobin: 2 g (men), 1.5 g (women)

• Ferritin: 1 g (men), 0.6 g (women)

• Hemosiderin: 300 mg

• Myoglobin: 200 mg

• Tissue enzymes (heme and nonheme): 150 mg

• Transport-iron compartment: 3 mg

Iron absorption

Ascorbic acid is the only common food element known to increase nonheme iron absorption.

Iron Deficiency Anemia

Image

By permission of the publisher. From Tefferi A, Li C. In Atlas of Clinical Hematology. Edited by JO Armitage. Philadelphia, Current Medicine, 2004.

The average American diet, which contains 6 mg of elemental iron/1000 kcal of food, is adequate for iron homeostasis. Of about 15 mg/day of dietary iron, adults absorb only 1 mg, which is the approximate amount lost daily by cell desquamation from the skin and intestine. In iron depletion, absorption increases due to the suppression of hepcidin, a key regulator of iron metabolism; however, absorption rarely increases to > 6 mg/day unless supplemental iron is added (1). Children have a greater need for iron and appear to absorb more to meet this need.

Because nonheme iron is poorly absorbed, dietary iron barely meets the daily requirement for most people. Even so, men who eat a typical Western diet are unlikely to become iron deficient solely as a result of dietary deficiency. However, even modest losses, increased requirements, iatrogenic phlebotomy, or decreased caloric intake can contribute to iron deficiency.

Blood loss is the major cause of iron deficiency. In men and postmenopausal women, the most frequent cause of blood loss is chronic occult bleeding, usually from the gastrointestinal tract (eg, due to peptic ulcer disease, malignancy, hemorrhoids, or vascular ectasias). Intestinal bleeding due to hookworm infection is a common cause in low-resource countries. In premenopausal women, cumulative menstrual blood loss (mean, 0.5 mg iron/day) is a common cause. Less common causes include urinary blood loss, recurrent pulmonary hemorrhage (see Diffuse Alveolar Hemorrhage) and chronic intravascular or traumatic (exercise-induced) hemolysis when the amount of iron released during hemolysis exceeds the plasma haptoglobin-binding capacity.

Increased iron requirements may contribute to iron deficiency. From birth to age 2 and during adolescence, when rapid growth requires a large iron intake, dietary iron often is inadequate. During pregnancy, the fetal iron requirement increases the maternal iron requirement (see Anemia in Pregnancy) despite the absence of menses. Lactation also increases the iron requirement.

Decreased iron absorption can result from gastrectomy or malabsorption syndromes such as celiac disease, atrophic gastritis, Helicobacter pylori infection, achlorhydria, short bowel syndrome, and rarely IRIDA (iron-refractory iron deficiency anemia). Rarely, absorption is decreased by dietary deprivation due to undernutrition.

Most symptoms of iron deficiency are due to anemia. Such symptoms include fatigue, loss of stamina, shortness of breath, weakness, dizziness, and pallor. Another common symptom is restless leg syndrome (RLS), which is an unpleasant urge to move the legs during periods of inactivity.

Koilonychia

Image

DR P. MARAZZI/SCIENCE PHOTO LIBRARY

In addition to the usual manifestations of anemia, some uncommon symptoms occur in severe iron deficiency. Patients may have pica, an abnormal craving to eat nonfood substances (eg, ice, dirt, paint, starch, ashes). Other symptoms of severe deficiency include glossitis, cheilosis, and concave nails (koilonychia).

• Complete blood count (CBC), serum iron, iron-binding capacity, serum ferritin, transferrin saturation, reticulocyte count, red cell distribution width (RDW), and a peripheral blood smear

Iron deficiency anemia is suspected in patients with chronic blood loss or microcytic anemia, particularly if pica is present. In such patients, a CBC, serum iron and iron-binding capacity, and serum ferritin and reticulocyte count are obtained (see table Typical Serum Values for Iron, Iron-Binding Capacity, Ferritin, and Transferrin Saturation).

Iron and iron-binding capacity (and transferrin saturation) are measured because their relationship is important. Various tests exist; the range of normal values relates to the test used and varies from laboratory to laboratory. Serum iron level is low in iron deficiency and in many chronic diseases and is elevated in hemolytic disorders and in iron-overload syndromes. The iron-binding capacity increases in iron deficiency, while the transferrin saturation decreases.

Serum ferritin levels closely correlate with total body iron stores. The range of normal in most laboratories is 30 to 300 ng/mL (67.4 to 674.1 pmol/L), and the mean is 88 ng/mL (197.7 pmol/L) in men and 49 ng/mL (110.1 pmol/L) in women. Low levels (< 30 ng/mL [67.4 pmol/L]) are specific for iron deficiency. However, ferritin is an acute-phase reactant, and levels increase in inflammatory and infectious disorders (eg, hepatitis), and neoplastic disorders (especially acute leukemia, Hodgkin lymphoma, and gastrointestinal tract tumors). In these disorders, a serum ferritin level up to 100 ng/mL remains compatible with iron deficiency.

The reticulocyte count is low in iron deficiency. The peripheral smear generally reveals hypochromic red cells with significant anisopoikilocytosis, which is reflected in a high red cell distribution width (RDW).

The most sensitive and specific criterion for iron-deficient erythropoiesis is absent bone marrow stores of iron, although a bone marrow examination is rarely needed.

• Oral supplemental iron

• Parenteral iron

Iron therapy without pursuit of the cause is poor practice; a bleeding site should be sought even in cases of mild anemia.

Oral iron1

Parenteral iron causes a more rapid therapeutic response than oral iron does but can cause adverse effects, most commonly allergic reactions or infusion reactions (eg, fever, arthralgias, myalgias). Severe anaphylactoid reactions

• Patients who do not tolerate oral iron

• Patients for whom oral iron is ineffective

• Patients who steadily lose large amounts of blood because of capillary or vascular disorders (eg, hereditary hemorrhagic telangiectasia)

• Patients with a need for expedient iron repletion due to severe anemia, elective surgery, or third trimester of pregnancy

The dose of parenteral iron is calculated based on weight and current hemoglobin level but generally an initial cumulative dose of 1000 mg is sufficient.

Oral iron therapy should continue for ≥ 6 months after correction of hemoglobin levels to replenish tissue stores, and iron studies should be rechecked at least 4 weeks after parenteral iron to ensure adequate repletion. The response to treatment is assessed by serial Hb measurements until normal RBC values are achieved. Hb rises little for 2 weeks but then rises 0.7 to 1 g/week until near normal, at which time the rate of increase tapers. Anemia should be corrected within 2 months. A subnormal response suggests continued hemorrhage, underlying infection or cancer, insufficient iron intake, or malabsorption of oral iron. If the symptoms of anemia, such as fatigue, weakness, and shortness of breath, do not abate following resolution of the anemia, an alternative cause should be sought.