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Iron Overload

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Aplastic anemia patients who receive repeated blood cell transfussions may develop iron overload. Iron from transfused red cells builds up in the blood and eventually accumulates in the heart, liver, pancreas, and endocrine organs. This excess iron may eventually damage vital organs and cause complications like liver disease, heart disease, and diabetes mellitus.

Normal body iron stores are 3-4 grams. Each unit of transfused red cells contains 200-250 mg of iron. Thus, a patient who receives 2 units of blood each month would accumulate approximately 5-6 g of extra iron in one year. Without treatment to remove excess iron, damage to the heart and other organs occurs in patients who have received as few as 100 units of blood, or 20 grams of excess iron. Visible signs of iron overload, such as bronze or slate grey skin pigmentation, don't usually appear until enough iron has accumulated to cause tissue damage.

In the United States, the only way to prevent or treat iron overload is with the iron chelating drug deferoxamine (Desferal). Desferal binds excess body iron and promotes its excretion by the kidneys in urine and via the bile in feces. Desferal is administered by subcutaneous or intravenous infusion by a small portable pump about the size of a Walkman. Typically the patient inserts a subcutaneous needle and wears the pump for 9-12 hours each day, usually at night while sleeping. Severely iron overloaded patients may need a continuous infusion through an indwelling central venous catheter. Several studies have demonstrated that regular chelation therapy with Desferal can remove excess body iron, prevent organ damage, and prolong life.

While Desferal is considered quite safe and effective, it has several drawbacks. The drug is expensive and occasionaly has some toxic side effects such a pain and swelling at the injection site, and rarely, impairment of vision and hearing or a general allergic/ anaphylactic reaction. Patients may dislike wearing the pump, and fail to carry out the treatment. A safe and effective oral medication is urgently needed. The oral iron chelator L1 is being studied in Europe, Canada and India; clinical trials will hopefully begin soon in the United States.

Who needs treatment for iron overload? Most hematologists agree that chelation therapy should begin well before organ damage occurs. Some physicians recommend beginning treatment after transfusions of 50 units of blood or when the serum ferritin exceeds 500 ng/ml (normal is 40-160), usually 1-2 years after diagnosis. Other hematologists may use a different cut-off. The important message for transfusion-dependent individuals is to be aware of this potential problem, and discuss monitoring and prevention with their hematologist.

- Jeanne Raisler