Iron is an essential element and plays a critical role in various metabolic processes in the body, including oxygen transport, energy production, and immune response. In certain disease states, an excess of iron can accumulate in the body. Primary iron overload is often inherited. Secondary iron overload usually arises from indications or causes such as transfusion, hemolysis, or excessive parenteral and/or dietary consumption of iron.* Secondary iron overload typically occurs in patients who have


Excess iron is deposited into organs throughout the body, which can damage the organs. Organs that commonly become damaged due to iron deposition are the liver, heart, and endocrine glands. Liver disease is the most common complication and may progress to cirrhosis. Patients who develop cirrhosis are at increased risk of hepatocellular carcinoma. The liver disease can present insidiously with nonspecific symptoms and signs, such as fatigue, and with right upper quadrant abdominal pain and hepatomegaly. Laboratory abnormalities of iron overload and hepatitis typically will be present well before clinical symptoms develop. Liver disease is the most common cause of death. Cardiomyopathy with heart failure is the 2nd most common fatal complication. Hyperpigmentation (bronze diabetes) and porphyria cutanea tarda are common, as is symptomatic arthropathy.


The treatment for iron overload is reduction therapy. This is most commonly achieved through therapeutic phlebotomy. In patients with an acceptable hemoglobin level, phlebotomy can initially be prescribed every 1 to 2 weeks until serum ferritin is brought within acceptable levels (approximately 50ug/L). Then, a schedule of periodic phlebotomy can be maintained, generally every 2 to 3 months, according to the serum ferritin levels achieved. When serum ferritin remains >1000 ng/ml, the risk of liver damage increases, and life expectancy decreases dramatically.

In patients with hemoglobin levels that do not tolerate therapeutic phlebotomy, iron chelation therapy becomes an option. Potential agents include parental deferoxamine and oral agents deferasirox and deferiprone. Deferoxamine is a parental treatment that requires prolonged infusions of up to 8 to 12 hours with multiple administrations per week to be effective. Subcutaneous infusion is preferred for treating chronic overload, whereas intravenous infusion is reserved for acute toxicity. 

Deferoxamine is the drug traditionally used for iron chelation therapy. 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, gastrointestinal 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. 

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. Deferiprone can also be used in combination with deferasirox because they have different mechanisms of action. 

Patients who are not treated or inadequately treated have lower survival rates than those who are adequately treated. Patients who are inadequately treated develop liver cirrhosis, hepatocellular carcinoma, pancreatic fibrosis, and diabetes at higher rates. Patients with severe liver damage due to inadequately treated hemochromatosis can receive a liver transplant.

MexBrain is developing a new treatment against acute iron toxicity, due mostly to secondary iron overload disorders. Using a dialysis machine and MEX-CD1, the treatment focuses on the free iron chelation from the blood. A first clinical trial is starting soon in France (Lyon) to explore the safety, feasibility and extraction capability of this new treatment in secondary iron overload disorders.  

* From Iron Overload, Lisa A. McDowell; Pujitha Kudaravalli; Richard J. Chen; Kristin L. Sticco