Iron Chelation and Sickle Cell Disease

High levels of iron in the body can cause life-threatening conditions, such as liver disease, heart problems, and diabetes. Excessive iron (often called “iron overload”) is caused by some genetic disorders, such as hereditary haemochromatosis. However, it also can happen after high numbers of blood transfusions.

People with sickle cell disease (SCD) can develop iron overload, even when transfusions are only done when needed. Excess iron causes people with SCD to have more painful episodes, more organ failure, and a shorter life expectancy.^1,2

Iron chelation therapy is a common way to reduce iron overload during chronic blood transfusions. Several different medications help remove iron from the body. However, it is still better to prevent iron overload by reducing the need for blood transfusions.

What is iron chelation therapy?

For people who receive multiple blood transfusions, iron chelation therapy is an important part of treatment. This is because some types of transfusions increase your red blood cell count and levels of hemoglobin, which contains iron. Iron chelation therapy uses a medicine that chelates (grabs and binds) iron and helps remove it from the body in urine and feces.³

Another way to remove iron from the body is phlebotomy (blood draw). However, people with SCD usually have a low red blood cell count (anemia) and should not have blood removed. This is why drugs that chelate and remove iron are typically used.^3,4

When possible, it is better to reduce the risk of iron overload than to use iron chelation therapy. Excess iron from transfusions can be minimized by:⁵

• Using transfusions only when appropriate
• Using medicines that reduce the need for transfusions (such as hydroxyurea)
• Using exchange transfusions instead of simple transfusions

How is iron chelation therapy used in sickle cell disease?

Iron chelation therapy results in better overall survival in SCD, especially when it is started early. When you should start chelation therapy depends on:^6,7

• The number and type of transfusions you have had
• The amount of iron in your liver and heart
• The degree of your liver and heart damage

People with SCD may begin iron chelation therapy after 1 to 2 years of transfusions or when iron levels hit a certain level. Doctors may monitor your iron levels by measuring the amount of ferritin (a protein that stores iron) in the blood using a blood draw. Ferritin levels are usually monitored every 3 to 4 months during chronic transfusion therapy and at every transfusion.⁴

Doctors may also measure the amount of iron in your heart and liver. This is typically done using an MRI at the start of chelation therapy and then every 1 to 2 years during chronic transfusion therapy.⁴

What are some iron chelation drugs?

There are 3 drugs used in iron chelation therapy:

• Deferoxamine (Desferal)
• Deferiprone (Ferriprox)
• Deferasirox (Exjade, Jadenu)

Deferoxamine is given by intravenous (into the vein), IM (into the muscle), or subcutaneous (under the skin) infusion. Deferiprone and deferasirox are given orally. Clinical trials have shown that these medications reduce iron levels in the body and decrease the risk of developing liver and heart complications. The type and amount of iron chelation drugs you use depends on your:^4,8,9

• Age
• Weight
• Iron levels
• Frequency of blood transfusions
• Amount of organ damage

Most people require changes in their dosage based on their response to the medicine. In some cases, a combination of 2 chelation drugs may be needed.⁴

What are the side effects of iron chelation therapy?

Side effects of deferoxamine include:^10,11

• Vision and hearing loss
• Abdominal pain
• Diarrhea
• Nausea and vomiting
• Low blood pressure
• Anaphylaxis (severe allergic reaction)

The risk for vision and hearing loss is higher when more deferoxamine is used. Your doctor may adjust your dose of deferoxamine to reduce the risk. Your doctor may monitor your hearing and eyesight every 6 to 12 months. They may also monitor your liver and kidney function every few months.¹²

Side effects of deferiprone include:^8,13

• Liver problems
• Low white blood cell count
• Joint stiffness
• Nausea and abdominal pain

Side effects of deferasirox include:¹⁴

• Kidney and liver damage
• Abdominal pain
• Nausea and vomiting
• Back pain
• Skin rash

If you are taking deferasirox or deferiprone, doctors may monitor your kidney and liver function and complete blood count every month.

These are not all the possible side effects of iron chelation drugs. Talk to your doctor about what to expect or if you experience any changes that worry you.