Iron Deficiency Anemia

Iron deficiency anemia develops when body stores of iron drop too low to support normal red blood cell (RBC) production. Inadequate dietary iron, impaired iron absorption, bleeding, or loss of body iron in the urine may be the cause. Iron equilibrium in the body normally is regulated carefully to ensure that sufficient iron is absorbed in order to compensate for body losses of iron (see the image below).

The total body iron in a 70-kg man is about 4 g. This is maintained by a balance between absorption and body losses. Although the body only absorbs 1 mg daily to maintain equilibrium, the internal requirement for iron is greater (20-25 mg). An erythrocyte has a lifespan of 120 days so that 0.8% of red blood cells are destroyed and replaced each day. A man with 5 L of blood volume has 2.5 g of iron incorporated into the hemoglobin, with a daily turnover of 20 mg for hemoglobin synthesis and degradation and another 5 mg for other requirements. Most of this iron passes through the plasma for reutilization. Iron in excess of these requirements is deposited in body stores as ferritin or hemosiderin.

Signs and symptoms

Patients with iron deficiency anemia may report the following:

• Fatigue and diminished capability to perform hard labor
• Leg cramps on climbing stairs
• Craving ice (in some cases, cold celery or other cold vegetables) to suck or chew
• Poor scholastic performance
• Cold intolerance
• Reduced resistance to infection
• Altered behavior (eg, attention deficit disorder)
• Dysphagia with solid foods (from esophageal webbing)
• Worsened symptoms of comorbid cardiac or pulmonary disease

Findings on physical examination may include the following:

• Impaired growth in infants
• Pallor of the mucous membranes (a nonspecific finding)
• Spoon-shaped nails (koilonychia)
• A glossy tongue, with atrophy of the lingual papillae
• Fissures at the corners of the mouth (angular stomatitis)
• Splenomegaly (in severe, persistent, untreated cases)
• Pseudotumor cerebri (a rare finding in severe cases)

Diagnosis

Useful tests include the following:

• Complete blood count
• Peripheral blood smear
• Serum iron, total iron-binding capacity (TIBC), and serum ferritin
• Evaluation for hemosiderinuria, hemoglobinuria, and pulmonary hemosiderosis
• Hemoglobin electrophoresis and measurement of hemoglobin A 2 and fetal hemoglobin
• Reticulocyte hemoglobin content

Tests useful for establishing the etiology of iron deficiency anemia and excluding or establishing a diagnosis of another microcytic anemia include the following:

• Stool testing
• Incubated osmotic fragility testing
• Measurement of lead in tissue
• Bone marrow aspiration

CBC results in iron deficiency anemia include the following:

• Low mean corpuscular volume (MCV)
• Low mean corpuscular hemoglobin concentration (MCHC)
• Elevated platelet count (>450,000/µL) in many cases
• Normal or elevated white blood cell count

Peripheral smear results in iron deficiency anemia are as follows:

• RBCs are microcytic and hypochromic in chronic cases
• Platelets usually are increased
• In contrast to thalassemia, target cells are usually not present, and anisocytosis and poikilocytosis are not marked
• In contrast to hemoglobin C disorders, intraerythrocytic crystals are not seen

Results of iron studies are as follows:

• Low serum iron and ferritin levels with an elevated TIBC are diagnostic of iron deficiency
• A normal serum ferritin can be seen in patients who are deficient in iron and have coexistent diseases (eg, hepatitis or anemia of chronic disorders)

Management

Treatment of iron deficiency anemia consists of correcting the underlying etiology and replenishing iron stores. Iron therapy is as follows:

• Oral ferrous iron salts are the most economical and effective form
• Ferrous sulfate is the most commonly used iron salt
• Better absorption and lower morbidity have been claimed for other iron salts
• Toxicity is generally proportional to the amount of iron available for absorption
• Reserve parenteral iron for patients who are either unable to absorb oral iron or who have increasing anemia despite adequate doses of oral iron
• Reserve transfusion of packed RBCs for patients who are experiencing significant acute bleeding or are in danger of hypoxia and/or coronary insufficiency