An Overview of Iron Overload

Iron overload is an excess storage of iron in the body. It can occur for a few different reasons. Primary iron overload is caused by hemochromatosis, an inherited condition. But it may also develop secondary to multiple blood transfusions, which may be needed by those with types of blood cancer. Iron overload can damage the heart, liver, and other organs if untreated.

Symptoms

In 75% of the cases, a person with iron overload will have no symptoms, although feelings of fatigue may begin early in the course of the condition.

However, once iron has built up in various organs, you may begin to experience more prominent symptoms. These can include:

• Joint pain (when in the knuckles, this is called "iron fist")
• Abdominal pain
• Loss of sex drive
• Skin colored gray or bronze

Untreated, the accumulation of iron can lead to:

• Heart failure
• Infertility
• Diabetes
• Cirrhosis of the liver
• Arthritis
• Hypothyroidism (under-active thyroid)
• Impaired growth
• Erectile dysfunction
• Cancer
• Depression

Some evidence also suggests bacterial infection may be one of the consequences of iron overload, as iron buildup in the white blood cells impairs their ability to fight invading organisms.

Causes

Iron has a very important role in your body. It plays a part in many biological processes, including the synthesis of DNA when cells divide and the transportation of oxygen from the lungs to cells and tissues.

Iron that you take in through food generally binds to a protein called transferrin and circulates around in your blood plasma. For the most part, this iron is used to form hemoglobin, the substance in red blood cells that transports the oxygen you breathe into your tissues. Leftover iron is stored in the liver for future use.

The human body does not have the ability to purposefully remove or excrete excess iron, although some iron is lost in normal processes such as the shedding of skin cells. Once the body’s maximum iron storage capacity is reached, iron begins to build up in other parts of the body, leading to iron overload.

When iron has overwhelmed the body’s ability to safely store it, it can cause harm in a number of ways:

• When there is more iron in the body than transferrin for it to bind to, it circulates around by itself as non-transferrin-bound iron (NTBI). This form of iron is toxic to the body and causes damage to tissues and organs at a cellular level.
• Excessive iron accumulates in the heart, lungs, brain, endocrine glands, liver, and even the bone marrow.

Hemochromatosis

Hemochromatosis is a common hereditary disorder seen in as many as 1 in 300 individuals. It is caused by mutations in genes that increase the absorption of iron from the diet.

There are several variations, with some being inherited in an autosomal recessive manner. In this case, the condition only becomes apparent if an individual receives the mutation from both parents, who may be asymptomatic carriers.

Transfusion-Related Iron Overload

In healthy individuals, only about 1 to 2 milligrams (mg) of iron is turned over in a given day—that is, iron that’s taken in from the diet and lost through the shedding of skin cells and gastrointestinal cells, for instance.

Red blood cell transfusions deliver a very large amount of iron, which can be a concern. A single unit of packed red blood cells (PRBCs) contains about 200 to 250 mg of iron. Most often, patients receive two units each time they are transfused, so that’s an extra 500 mg of iron in just one day.

Multiple blood transfusions are a fact of life for some patients with leukemia, lymphoma, and myeloma. Transfusions are used to improve blood cell counts and to treat the signs and symptoms of anemia, such as fatigue, foggy thinking, shortness of breath and weakness. And while the decision to administer these transfusions means the pros outweigh the cons in these patients, multiple blood transfusions over time can potentially cause iron overload.

Patients with blood and marrow cancers, such as leukemia and lymphoma, usually require a greater number of transfusions after chemotherapy, after radiotherapy to their pelvic region, or following stem cell transplantation.

Patients with myelodysplastic syndromes (MDS) often have a persistently low hemoglobin and many are transfusion-dependent, putting them at high risk for iron overload. MDS with sideroblastic anemia may also cause patients to absorb an excessive amount of iron from their food, making the problem even worse.

Diagnosis

Iron overload occurs over time, and often patients will not show any signs. It is more likely that iron overload will be detected by laboratory results before the person has symptoms.

The most common test to assess iron saturation is called serum ferritin level. This is a blood test that may be done on a regular basis for high-risk individuals.

Healthy men usually have a serum ferritin of 24 to 336 micrograms per liter (mcg/L); healthy women's results are usually 12 to 307 mcg/L. Serum ferritin levels increase as the amount of NTBI increases in the blood, and results that are greater than 1,000 mcg/L indicate iron overload.

Other diseases and conditions can also cause large amounts of ferritin to be released in the circulation, however, which can make a single elevated reading unreliable. This is why testing on a regular basis is the norm.

Genetic testing may be done to confirm hereditary hemochromatosis. This is a blood test looking for the HFE gene defect. This may also be done as a screening test to detect the defect before it becomes symptomatic and damage has occurred.

Imaging studies can also reveal findings suggestive of iron overload. Magnetic resonance imaging (MRI) may be used to detect iron accumulation in the liver and the heart. However, iron deposition is not reliably predicted by MRI in some instances, such as when iron deposition occurs in the pancreas.

MRI may be used together with a liver biopsy to diagnose iron overload or these can be done independently. A liver biopsy can check iron concentration. While this test may give slightly more accurate results than serum ferritin levels, it requires a fairly invasive procedure that can lead to complications, such as infection and bleeding.

Treatment

There are two main ways that iron overload is treated—therapeutic phlebotomy and iron chelation therapy.

Therapeutic Phlebotomy

Therapeutic phlebotomy is the quickest and most effective way to get iron levels down in a patient. Unfortunately, it cannot be used on patients that remain anemic. Therefore, it is typically reserved for people with hemochromatosis or people whose leukemia or lymphoma is in remission.

During a therapeutic phlebotomy, a nurse or healthcare provider will insert a large needle into your vein, usually in your arm. They will then remove about 500 milliliters (ml) of blood from your body over about 15 to 30 minutes. If you have ever donated blood, the process is similar.

This amount of blood contains about 250 mg of iron. As this iron is removed through your blood, your liver releases some of its stores and eventually the amount of circulating iron can be returned to normal ranges.

Phlebotomy may be done once or twice a week as necessary to reach the goal of serum ferritin levels of 50 to 100 mcg/L.

Iron Chelation Therapy

Iron chelation therapy uses medications that bind, or chelate, iron and facilitate its removal from the body. The goal of this type of therapy is to remove excess iron from the blood and organ tissues. Although this therapy works well on plasma iron and liver deposits, it is not as effective in removing iron deposits from the heart.

Iron chelator medications—Exjade (deferasirox) and Ferriprox (deferiprone)—are effective at reducing NTBI levels, but these levels rebound quickly if the therapy is discontinued. Therefore, these medications must be taken exactly as directed for them to work properly. This can be a big commitment for some patients.

Iron chelators are also not without side effects, and the risks and benefits of iron chelation need to be weighed carefully.

Diet

In addition to these therapies, your healthcare provider may make recommendations to lower the amount of iron you absorb through your food as well.

Coping

For those with hereditary hemochromatosis and iron overload, regular phlebotomy and testing of iron and ferritin levels will be necessary throughout life. You should avoid iron-fortified foods and iron-containing vitamins and supplements.

If you require blood transfusions for blood cancer or other disorders, there are things that you can do to ensure that your iron levels are monitored properly. Inform your current healthcare team of your past blood transfusion history. You may have received PRBCs years ago for a completely unrelated condition, but your healthcare provider needs to know about that now.

You should also try to keep track of each transfusion you receive. This may not be easy, and there may be times in your therapy when it seems like all you do is get transfused, but it will be important later on.

Your healthcare team should begin to monitor your serum ferritin levels once you have received about 20 lifetime units of blood. If you usually get two units at a time, this may only be 10 transfusions. If they do not automatically order it, you should request it.

A Word From Verywell

Iron overload can come as a surprise for people with hereditary hemochromatosis who have no symptoms. It may also be an anticipated consequence of multiple blood transfusions in those who require them, especially people with blood or marrow cancer. If untreated, iron overload can lead to serious organ damage and even death, but effective treatments are available.