Iron Deficiency Anemia Treatment & Management

Updated: Nov 14, 2016
  • Author: James L Harper, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Treatment

Approach Considerations

Medical care starts with establishing the diagnosis and reason for the iron deficiency. In most patients, the iron deficiency should be treated with oral iron therapy, and the underlying etiology should be corrected so the deficiency does not recur. However, avoid giving iron to patients who have a microcytic iron-overloading disorder (eg, thalassemia, sideroblastic anemia). Do not administer parenteral iron therapy to patients who should be treated with oral iron, as anaphylaxis may result.

Uncommonly, postmenopausal women are unresponsive to iron supplementation, including parenteral iron, because they have primary defective iron reutilization due to androgen deficiency. This condition responds only to androgen replacement. Danazol is a reasonable choice for these patients, as it is less masculinizing. [7, 8]

Transfer of a patient rarely is required for treatment of simple iron deficiency anemia. However, it may be necessary to identify the etiology of the anemia, such as occult blood loss undetected with chemical testing of stool specimens; for identification of a source of bleeding that requires endoscopic examinations or angiography; or for treatment of an underlying major illness (eg, neoplasia, ulcerative colitis).

The British Society of Gastroenterology guidelines suggest that all patients require iron supplementation and that parenteral iron can be used if oral preparations are not well tolerated. The guidelines also state that blood transfusions should be reserved for patients who are at risk for, or who have, cardiovascular instability due to their anemia. [15]

Treatment guidelines from the American College of Physicians (ACP) for adult patients with anemia and iron deficiency include the following [16] :

  • A restrictive red blood cell transfusion strategy is recommended for hospitalized patients with coronary heart disease, with the trigger hemoglobin threshold lowered to 7-8 g/dL (recommendation: weak; quality of evidence: low)
  • Erythropoiesis-stimulating agents are not recommended for patients with mild to moderate anemia and either congestive heart failure or coronary heart disease (recommendation: strong; quality of evidence: moderate)

Go to Anemia, Sideroblastic Anemias, and Chronic Anemia for more information on these topics.

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Iron Therapy

Oral ferrous iron salts are the most economical and effective medication for the treatment of iron deficiency anemia. Of the various iron salts available, ferrous sulfate is the one most commonly used.

Although the traditional dosage of ferrous sulfate is 325 mg (65 mg of elemental iron) orally three times a day, lower doses (eg, 15-20 mg of elemental iron daily) may be as effective and cause fewer side effects. To promote absorption, patients should avoid tea and coffee and may take vitamin C (500 units) with the iron pill once daily. [17]

However, a study by Moretti et al suggests that the standard dosing of iron supplements may be counterproductive.Their research focuses on the role of hepcidin, which regulates systemic iron balance, partly in response to plasma iron levels. They found that when a large oral dose of iron is taken in the morning, the resulting increase in the plasma iron level stimulates an increase in hepcidin, which in turn will interfere with the absorption of an iron dose taken later in the day; indeed, suppression of iron absorption could last as long as 48 hours. [18, 19]

In one part of their study, twice-daily doses of 60 mg or greater resulted in an increase in serum hepcidin levels after the first dose and a 35-45% decrease in the amount of iron that was absorbed from the second dose. With increasing doses, study subjects showed an increase in the absolute amount of iron absorbed, but a decrease in the fraction of the dose that was absorbed: a sixfold increase in iron dose (from 40 mg to 240 mg) resulted in only a threefold increase in iron absorbed. In another part of the study, total iron absorbed from a morning and an afternoon dose on one day plus a morning dose the next day was not significantly greater than absorption from two consecutive morning doses. [18]

Moretti et al concluded that providing lower dosages and avoiding twice-daily dosing will maximize fractional iron absorption. They note that although the short-term effects observed in their study will require confirmation in longer-term studies, their results support supplementation with 40-80 mg of iron taken every other day. A possible additional benefit of this schedule may be that improving absorption will reduce gastrointestinal exposure to unabsorbed iron and thereby reduce adverse effects from supplements. [18, 19]

Claims are made that other iron salts (eg, ferrous gluconate) are absorbed better than ferrous sulfate and have less morbidity. Generally, the toxicity is proportional to the amount of iron available for absorption. If the quantity of iron in the test dose is decreased, the percentage of the test dose absorbed is increased, but the quantity of iron absorbed is diminished.

Some authors advocate the use of carbonyl iron because of the greater safety for children who ingest their mothers’ medication. Decreased gastric toxicity is claimed but not clearly demonstrated in human trials. Bioavailability is approximately 70% of a similar dose of ferrous sulfate.

The usual benchmark for successful iron supplementation is a 2-g/dL increase in the hemoglobin (Hb) level in 3 weeks. [20] However, a meta-analysis of five randomized controlled trials concluded that in patients receiving oral iron supplementation, an Hb measurement on day 14 that shows an increase of 1.0 g/dL or more over baseline is an accurate predictor of longer-term and sustained response to continued oral therapy. The authors suggest that, "Day-14 Hb may be a useful tool for clinicians in determining whether and when to transition patients from oral to IV iron." [21]

Parenteral iron therapy

Reserve parenteral iron for patients who are either unable to absorb oral iron or who have increasing anemia despite adequate doses of oral iron. It is expensive and has greater morbidity than oral preparations of iron. Parenteral iron has been used safely and effectively in patients with inflammatory bowel disease (eg, ulcerative colitis, Crohn disease), [22] as the ferrous sulfate preparations may aggravate the intestinal inflammation.

In July 2013, the FDA approved ferric carboxymaltose injection (Injectafer) for the intravenous treatment of iron deficiency anemia in adults who either cannot tolerate or have not responded well to oral iron. The drug is also indicated for the treatment of iron deficiency anemia in adults with non–dialysis-dependent chronic kidney disease. Approval was based on two clinical studies in which the drug was given at a dose of 15 mg/kg body weight, up to a maximum of 750 mg, on two occasions at least 7 days apart, up to a maximum cumulative dose of 1500 mg of iron. [23, 24, 25]

A review of the safety of intravenous (IV) iron preparations, particularly in patients with chronic kidney disease, by Kalra and Bhandari concluded that high molecular weight iron dextrans are associated with increased risks, so their use for IV therapy should be avoided. The second- and third-generation IV irons are considered equally efficacious in treating iron deficiency in equivalent doses, but iron isomaltoside seems to have a lower frequency of serious and severe hypersensitivity reactions. [26]

 

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Management of Hemorrhage

Surgical treatment consists of stopping hemorrhage and correcting the underlying defect so that it does not recur. This may involve surgery for treatment of either neoplastic or nonneoplastic disease of the gastrointestinal (GI) tract, the genitourinary (GU) tract, the uterus, and the lungs.

Reserve transfusion of packed red blood cells (RBCs) for patients who either are experiencing significant acute bleeding or are in danger of hypoxia and/or coronary insufficiency.

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Dietary Measures

On a worldwide basis, diet is the major cause of iron deficiency. However, to suggest that iron-deficient populations correct the problem by the addition of significant quantities of meat to their diet is unrealistic.

The addition of nonheme iron to national diets has been initiated in some areas of the world. Problems encountered in these enterprises include changes in taste and appearance of food after the addition of iron and the need to supplement foodstuffs that are consumed by most of the population in predictable quantities. In addition, many dietary staples, such as bread, contain iron chelators that markedly diminish the absorption of the iron supplement (phosphates, phytates, carbonates, oxalates, tannates).

In North America and Europe, persons on an iron-poor diet need to be identified and counseled on an individual basis. Educate older individuals on a “tea and toast” diet about the importance of improving their diet (for example,tea strongly blocks iron absorption), and place them in contact with community agencies that will provide them with at least one nutritious meal daily. Patients who have diet-related iron deficiency due to pica need to be identified and counseled to stop their consumption of clay and laundry starch.

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Activity Restriction

Restriction of activity is usually not required.

Patients with moderately severe iron deficiency anemia and significant cardiopulmonary disease should limit their activities until the anemia is corrected with iron therapy. If these patients become hypoxic or develop evidence of coronary insufficiency, they should be hospitalized and placed on bed rest until improvement of their anemia can be accomplished by transfusion of packed RBCs. Obviously, such decisions must be made on an individual basis and will depend on the severity of the anemia and the comorbid conditions.

March hemoglobinuria can produce iron deficiency, and its treatment requires modification of activity. Cessation of jogging or wearing sneakers while running usually diminishes the hemoglobinuria.

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Prevention

Certain populations are at sufficiently high risk for iron deficiency to warrant consideration for prophylactic iron therapy. These include pregnant women, women with menorrhagia, [27] consumers of a strict vegetarian diet, infants, [28] adolescent girls, and regular blood donors.

Pregnant women have been given supplemental iron since World War II, often in the form of all-purpose capsules containing vitamins, calcium, and iron. If the patient is anemic (hemoglobin < 11 g/dL), administer the iron at a different time of day than calcium because calcium inhibits iron absorption.

The practice of routinely administering iron to pregnant females in affluent societies has been challenged. Nevertheless, providing prophylactic iron therapy during the last half of pregnancy continues to be advisable, except in settings where careful follow-up for anemia and methods for measurement of serum iron and ferritin are readily available.

Iron supplementation of the diet of infants is advocated. Premature infants require more iron supplementation than term infants. Infants weaned early and fed bovine milk require more iron because the higher concentration of calcium in cow milk inhibits absorption of iron. Usually, infants receive iron from fortified cereal. Additional iron is present in commercial milk formulas.

Iron supplementation in populations living on a largely vegetarian diet is advisable because of the lower bioavailability of inorganic iron than heme iron.

The addition of iron to basic foodstuffs in affluent nations where meat is an important part of the diet is of questionable value and may be harmful. The gene for familial hemochromatosis (HFe gene) is prevalent (8% of the US white population). Excess body iron is postulated to be important in the etiology of coronary artery disease, strokes, certain carcinomas, and neurodegenerative disorders because iron is important in free radical formation.

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Consultations

Surgical consultation often is needed for the control of hemorrhage and treatment of the underlying disorder. In the investigation of a source of bleeding, consultation with certain medical specialties may be useful to identify the source of bleeding and to provide control.

Among the medical specialties, gastroenterology is the most frequently sought consultation. Endoscopy has become a highly effective tool in identifying and controlling GI bleeding. If bleeding is brisk, angiographic techniques may be useful in identifying the bleeding site and controlling the hemorrhage. Radioactive technetium labeling of autologous erythrocytes also is used to identify the site of bleeding. Unfortunately, these radiographic techniques do not detect bleeding at rates less than 1 mL/min and may miss lesions that bleed only intermittently.

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Long-Term Monitoring

Monitor patients with iron deficiency anemia on an outpatient basis to ensure that there is an adequate response to iron therapy and that iron therapy is continued until after correction of the anemia to replenish body iron stores. Follow-up also may be important to treat any underlying cause of the iron deficiency.

Response to iron therapy can be documented by an increase in reticulocytes 5-10 days after the initiation of iron therapy. The hemoglobin concentration increases by about 1 g/dL weekly until normal values are restored. These responses are blunted in the presence of sustained blood loss or coexistent factors that impair hemoglobin synthesis.

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