From the Guidelines
Iron overload in patients is most commonly caused by hereditary hemochromatosis, multiple blood transfusions, chronic liver diseases, and excessive iron supplementation or consumption. The body's inability to efficiently eliminate excess iron leads to its accumulation in tissues over time, potentially damaging organs like the liver, heart, and pancreas.
Causes of Iron Overload
- Hereditary hemochromatosis, a genetic disorder that increases iron absorption from food 1
- Multiple blood transfusions, which directly add iron to the body 1
- Chronic liver diseases such as alcoholic liver disease and hepatitis C 1
- Certain anemias like thalassemia and sideroblastic anemia, where ineffective red blood cell production leads to increased iron absorption 1
- Excessive iron supplementation or consumption 1
- Rare conditions like African iron overload, caused by consuming food or beverages prepared in iron cookware 1
Diagnosis and Treatment
Diagnosis of iron overload involves assessing the magnitude of iron accumulation, which can be done through serum ferritin level tests, liver iron concentration measurements, and non-invasive MRI techniques 1. Treatment typically involves phlebotomy (blood removal) for hemochromatosis patients, with sessions removing 500ml of blood weekly until iron levels normalize, then maintenance sessions every 2-4 months 1. For transfusion-dependent patients, iron chelation therapy with medications like deferasirox, deferiprone, or deferoxamine is used to bind and remove excess iron 1. According to the most recent guideline, the ESPEN micronutrient guideline recommends iron removal by blood donation/phlebotomy in the absence of anemia and chelation in transfusion-associated overload in hematologic diseases 1.
From the FDA Drug Label
Deferasirox tablets are an iron chelator indicated for the treatment of chronic iron overload due to blood transfusions in patients 2 years of age and older. The patient may have iron overload due to blood transfusions.
- Chronic iron overload can occur in patients who receive frequent blood transfusions, leading to an accumulation of excess iron in the body. 2
From the Research
Causes of Iron Overload
Iron overload in a patient can occur due to various reasons, including:
- Genetic causes, such as hereditary hemochromatosis, which is an autosomal recessive disorder that disrupts iron homeostasis, resulting in systemic iron overload 3
- Secondary causes, such as frequent blood transfusions, exogenous iron intake, or certain hematological diseases like dyserythropoietic syndrome or chronic hemolytic anemia 4
- Inherited iron overload disorders, which include several disorders characterized by iron accumulation in tissues, organs, or even single cells or subcellular compartments, determined by mutations in genes directly involved in hepcidin regulation, cellular iron uptake, management and export, iron transport and storage 5
Types of Iron Overload Disorders
There are several types of iron overload disorders, including:
- Hemochromatosis, which includes five different genetic forms, all characterized by high transferrin saturation and serum ferritin, but with different penetrance and expression 5
- Ferroportin disease, which is due to loss-of-function mutation of SLC40A1 that impairs the iron export efficiency of ferroportin, causing iron retention in reticuloendothelial cell and hyperferritinemia with normal transferrin saturation 5
- Aceruloplasminemia, which is caused by defective iron release from storage and leads to mild microcytic anemia, low serum iron, and iron retention in several organs, including the brain, causing severe neurological manifestations 5
Diagnosis and Treatment
Diagnosis of iron overload disorders involves a sequential strategy that combines clinical, imaging, biochemical, and genetic data 5. Treatment of iron overload relies on two main therapies: blood removal and iron chelators 5. Phlebotomy is the mainstay of treatment for hereditary hemochromatosis and can help improve heart function, reduce abnormal skin pigmentation, and lessen the risk of liver complications 3. Iron chelators, such as deferasirox, can also be effective in reducing iron burden in patients with hereditary hemochromatosis 6.