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Secondary Iron Overload
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.
Secondary iron overload typically occurs in patients who have
Iron overload results from the following mechanisms:
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.
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.
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