Iron Overload in Thalassemia

Mechanisms of Iron Accumulation

The human body lacks a physiological mechanism to excrete excess iron, which accumulates from both regular blood transfusions and increased gastrointestinal absorption due to ineffective erythropoiesis, according to the American College of Cardiology 1
Transfusion-related iron overload occurs as each unit of packed red blood cells contains 200-250 mg of elemental iron that accumulates in the body with no active excretion mechanism, leading to significant iron accumulation over time in transfusion-dependent thalassemia patients, as stated by the American College of Cardiology 1

When iron levels exceed the binding capacity of transferrin, non-transferrin bound iron is released into circulation, as reported by the American College of Cardiology 1
This unbound iron enters cardiac myocytes through L-type calcium channels and can cause significant organ damage, according to the American College of Cardiology 1

Therapeutic intervention is required through iron chelation therapy to bind iron and promote its excretion, as well as phlebotomy in non-anemic patients with hereditary hemochromatosis, as stated by the American College of Cardiology 2
Chelation therapy aims to detoxify organs containing excess iron by binding to it and promoting excretion through urine and bile, according to the American College of Cardiology 2
Available chelators include deferoxamine, deferiprone, and deferasirox, each with different efficacy profiles and side effects, as reported by the American College of Cardiology 2
Phlebotomy is not feasible for thalassemia patients due to their underlying anemia, making chelation therapy the only option, as stated by the American College of Cardiology 2

In transfusion-dependent thalassemia, each unit of blood contains approximately 200 mg of iron, leading to significant iron accumulation over time with regular transfusions, according to the American Heart Association 3
Non-transfusion-dependent thalassemia patients develop iron overload primarily through increased gastrointestinal iron absorption, as stated by the American College of Cardiology 4

Cardiac iron loading is the leading cause of death in transfusion-dependent thalassemia patients, with cardiac complications accounting for approximately 70% of deaths, as reported by the American Heart Association 5, 6
Before the introduction of chelation therapy, patients with transfused but unchelated β-thalassemia typically died by age 10, primarily from cardiac complications, according to the American College of Cardiology 6

In thalassemia intermedia, patients may not initially require transfusions but may need them later in life to prevent complications, which then contributes to iron loading, as stated by the American College of Cardiology 4, 7
The introduction of improved chelation therapy has significantly increased life expectancy in thalassemia major, with median age at death improving to 35 years by 2000 in the UK, as reported by the National Health Service 7
Pregnancy in women with thalassemia requires careful monitoring of iron status and cardiac function, as increased blood consumption during pregnancy combined with interruption of chelation therapy may worsen iron overload, according to the American College of Obstetricians and Gynecologists 8