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Secondary Iron Overload

(Secondary Hemochromatosis)

by Candido E. Rivera, MD

Secondary iron overload results from excess absorption of iron, repeated blood transfusions, or excess oral intake, typically in patients with disorders of erythropoiesis. Diagnosis is with serum iron studies. Treatment is usually by iron chelation.

Etiology of Secondary Iron Overload

Secondary iron overload typically occurs in patients who have

  • Hemoglobinopathies (eg, sickle cell disease, thalassemia, sideroblastic anemias)

  • Congenital hemolytic anemias

  • Myelodysplasia

Iron overload results from the following mechanisms:

  • Increased iron absorption

  • Exogenous iron given to treat the anemia

  • Repeated blood transfusions (each unit of blood provides about 250 mg of iron; tissue deposition becomes significant when more than about 40 units of blood are transfused)

Increased iron absorption in patients with ineffective erythropoiesis may be partly due to the secretion, by erythroid precursors, of erythroferrone [ERFE], which suppresses hepcidin (an inhibitor of iron absorption).

Patients with hemoglobinopathies and congenital hemolytic anemias now typically live into adulthood, so complications of iron overload are now common and clinically important. In such patients, iron overload involving the heart, the liver, and endocrine organs has become a common cause of death, but survival can be prolonged by iron removal.

Diagnosis of Secondary Iron Overload

  • Measure serum ferritin and iron and transferrin saturation

Patients with ineffective erythropoiesis should be evaluated for secondary iron overload, which is diagnosed by measuring serum ferritin, serum iron, and transferrin saturation.

Treatment of Secondary Iron Overload

  • Usually iron chelation with deferasirox or deferoxamine, or sometimes deferiprone

Some patients can be treated with phlebotomy and given erythropoietin to maintain erythropoiesis. However, because it worsens anemia, phlebotomy is not recommended for many patients (eg, those with Hb level < 10 g/dL, those who are transfusion dependent, and those who develop symptoms of anemia after phlebotomy). Treatment in these patients is iron chelation. The goal of treatment is a transferrin saturation of < 50%.

Deferoxamine is the drug traditionally used for iron chelation therapy. It is given by a slow subcutaneous infusion overnight through a portable pump for 5 to 7 nights/wk or via 24-h IV infusion. Dose is 1 to 2 g in adults and 20 to 40 mg/kg in children. However, this therapy is complex to administer and requires an unusual time commitment from patients, resulting in a high rate of nonadherence. Important adverse effects include hypotension, GI disturbances, and anaphylaxis (acutely) and vision and hearing loss (with chronic use).

Deferasirox, an oral chelating agent, is an effective and increasingly used alternative to deferoxamine. Deferasirox reduces iron levels and prevents or delays onset of complications of iron overload. Initial dose is 20 mg/kg po once/day. Patients are monitored monthly with dose increases of up to 30 mg/kg once/day. Treatment can be interrupted when serum ferritin is < 500 ng/mL. Adverse effects (which occur in about 10% of patients) can include nausea, abdominal pain, diarrhea, and rash. Liver and kidney function may become abnormal; liver and kidney function tests should be done periodically (eg, monthly, sometimes more frequently for high-risk patients).

Deferiprone, another oral iron chelator, is indicated for the treatment of patients with transfusional iron overload due to thalassemia syndromes when chelation therapy with deferasirox or deferoxamine is inadequate. Initial dose is 25 mg/kg po tid. Maximum dose is 33 mg/kg po tid. Absolute neutrophil counts are obtained weekly to look for neutropenia (precedes agranulocytosis). Serum ferritin is measured every 2 to 3 mo; treatment is temporarily interrupted when levels are consistently < 500 μg/L.

Drugs Mentioned In This Article

  • Drug Name
    Select Trade
  • DESFERAL
  • EXJADE
  • FERRIPROX

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