Iron Overload: Too Much of a Good Thing

A Review of Iron Overload From Multiple Transfusions

Women Receiving a Blood Transfusion
Women Receiving a Blood Transfusion. Patrick Foto/Creative RF/Getty Images

Iron overload is a condition where there is more iron in the body than can be removed by the body. The technical term for iron overload is hemochromatosis. There are two major reasons for iron overload - 1) hereditary hemochromatosis or 2) transfusional hemochromatosis. Hereditary hemochromatosis is a condition passed down in families. Transfusional hemochromatosis occurs when a person requires multiple red blood cell (RBC) transfusions.

Iron is found inside hemoglobin, a protein inside of the RBC. The iron's job to help transport oxygen to all the tissues. Normally the body absorbs just enough iron from your diet to keep up with RBC production. If you don't eat enough foods with iron, your iron levels become low resulting in iron deficiency anemia. When RBCs get to the end of their life, the iron inside them is recycled to be used in new RBCs being produced.  

Why Do Multiple RBC Transfusions Cause Iron Overload?

Iron is found inside all of the RBCs in the unit of blood transfused. So every RBC transfusion a person receives is essentially an intravenous (IV) infusion of iron. The problem is that the body is limited in its ability to get rid of this excessive iron. Additionally, people with thalassemia absorb more iron than they need from their diet worsening the problem. 

Who Is at Risk for Transfusional Iron Overload?

Anyone who receives multiple RBC transfusions is at risk, but people who are dependent on transfusions are at highest risk.

This would include people with sickle cell disease who have had a stroke (or are at high risk for stroke), beta thalassemia major, Diamond Blackfan Anemiaaplastic anemia, and myelodysplastic syndrome among others. People with cancer who need multiple transfusions during treatment with chemotherapy or bone marrow transplantation are also at risk for transfusional iron overload.

 

How Does My Physician Monitor for Iron Overload?

People who are going to need lifelong transfusions are generally monitored closely for iron overload. In these patients, iron overload can be seen after 12 to 15 RBC transfusions. Iron overload is typically monitored with a blood test called ferritin initially. Ferritin represents the total amount of iron stored in your body. Ferritin is typically drawn on a schedule, every one to three months, so that your physician can see how it is trending (that is, is the value increasing?). Chelation, the term of medications used to remove iron, is typically started after the ferritin is greater than 1000 ng/mL. Unfortunately, ferritin levels are affected by things other than iron overload. Elevated ferritin levels can be seen during illness and inflammation. 

Because of the limitations with ferritin, other methods to assess iron overload were developed. Previously, iron overload was monitored with liver biopsies where a small piece of liver was removed and assessed for iron.

Currently, most people can be monitored with magnetic resonance imaging (MRI) of the liver and/or heart. The MRI can calculate a liver iron content (LIC) similar to the results of a liver biopsy.  Chelation is started when the LIC is greater than 3 mg per gram dry weight liver. Similarly, a MRI of the heart can measure the amount of iron located in the heart muscle.

What Complications Can Occur With Iron Overload?

Once all of the typical locations to store iron are no longer available, iron can then be stored in the liver, heart, pancreas, and endocrine organs (generally called glands). When iron is stored in these locations, it damages the organ. This can result in fibrosis or scarring of the liver, cardiomyopathy (disease of the heart muscle), diabetes mellitus (due to iron in the pancreas), hypothyroidism (low thyroid hormone levels) and hypogonadism (causing decreased libido and impotence in men and lack of menstrual cycles in women).  To prevent these serious and potentially life-threatening complications, iron overload is treated aggressively.  

How Is Transfusional Iron Overload Treated?

Iron overload from transfusions is treated with chelation therapy, medication given to remove iron from the body. There are three medications available.

  1. Deferoxamine (Desferal)
  2. Deferasirox (Jadenu or Exjade)
  3. Deferiprone (Ferriprox)

Therapeutic phlebotomy: If at some point you are able to discontinue transfusions, iron overload can be treated with serial phlebotomy.  Phlebotomy is a similar to blood donation where a large amount of blood is removed from the body.  Within the RBCs removed is iron and when these are replaced by the bone marrow it will use the excess iron stored in your body.  

Sources:

Schrier SL and Bacon BR. Chelation therapy for thalassemia and other iron overload states.  and Iron overload syndromes other than hereditary hemochromatosis. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA.

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