Why is iron overload a concern in thalassemia?

From the Guidelines

Iron overload is a major concern in thalassemia because it can lead to serious complications, including heart failure, cirrhosis, diabetes, and endocrine dysfunction, ultimately affecting morbidity, mortality, and quality of life. The primary reason for this concern is that patients with thalassemia require frequent blood transfusions to manage their anemia, with each unit of transfused blood containing approximately 200-250 mg of iron that the body cannot eliminate naturally 1. This leads to progressive iron accumulation in vital organs like the heart, liver, and endocrine glands. Additionally, ineffective erythropoiesis in thalassemia increases intestinal iron absorption, further contributing to iron overload 1.

Management of Iron Overload

Management of iron overload in thalassemia requires iron chelation therapy with medications such as deferasirox (Exjade, 20-40 mg/kg/day), deferoxamine (Desferal, 20-60 mg/kg/day via subcutaneous infusion), or deferiprone (Ferriprox, 75-100 mg/kg/day in three divided doses) 1.

• Treatment should begin after approximately 10-20 transfusions or when serum ferritin exceeds 1,000 ng/mL.
• Regular monitoring of iron levels through serum ferritin tests and specialized MRI techniques (T2* MRI) is essential to adjust chelation therapy and prevent organ damage.
• The goal of chelation therapy is to detoxify organs containing excess iron by binding the iron, removing it, and then excreting the compound in urine and bile 1.

Importance of Monitoring and Adjustment

Monitoring and adjusting chelation therapy based on liver iron and serum ferritin levels are crucial to prevent chelator-mediated toxicity and ensure the removal of cardiac iron 1.

• Compliance with iron chelation treatment is essential for long-term survival and prevention of acute cardiac failure.
• Long-term follow-up by a specialist center is necessary to achieve optimal outcomes and adjust treatment as needed 1.

Recent Guidelines and Recommendations

Recent guidelines emphasize the importance of individualized treatment plans, careful monitoring, and adjustment of chelation therapy to prevent iron overload complications in thalassemia patients 1.

• The use of combination therapy with daily subcutaneous deferoxamine and daily oral deferiprone has been suggested for long-term management of patients with impaired left ventricular function without decompensated heart failure.
• Treatment should be monitored by assessing clinical status, left ventricular ejection fraction, cardiac T2*, and ferritin trend 1.

From the FDA Drug Label

In a prospective, planned, pooled analysis of patients with thalassemia syndromes from several studies, the efficacy of deferiprone was assessed in transfusion-dependent iron overload patients in whom previous iron chelation therapy had failed or was considered inadequate due to poor tolerance The main criterion for chelation failure was serum ferritin > 2,500 mcg/L before treatment with deferiprone.

Iron overload in thalassemia is a concern because it can lead to transfusional iron overload, which can cause serious health issues. The fact that deferiprone therapy is used to treat iron overload in patients with thalassemia syndromes, and the main criterion for chelation failure is a serum ferritin level > 2,500 mcg/L, suggests that high iron levels are a significant concern in these patients.

• Key points about iron overload in thalassemia include:
  • Transfusional iron overload can occur in patients with thalassemia syndromes
  • High serum ferritin levels (> 2,500 mcg/L) are a criterion for chelation failure
  • Deferiprone therapy is used to treat iron overload in these patients 2

From the Research

Iron Overload in Thalassemia

Iron overload is a significant concern in thalassemia due to the potential for serious complications. The following points highlight the reasons why iron overload is a concern:

• Iron overload can lead to increased morbidity in both patients with transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) 3.
• The mechanisms driving iron loading include increased iron burden secondary to transfusion therapy in TDT and enhanced intestinal absorption secondary to ineffective erythropoiesis and hepcidin suppression in NTDT 3.
• Different organs are affected differently by iron overload in TDT and NTDT, owing to the underlying iron loading mechanism and rate of iron accumulation 3.

Complications of Iron Overload

The complications of iron overload in thalassemia include:

• End-organ damage, such as heart problems and cirrhosis 4, 5.
• Increased risk of mortality, particularly from heart failure 5.
• Other complications, such as endocrine abnormalities and liver damage 6.

Management of Iron Overload

The management of iron overload in thalassemia involves the use of iron chelators, such as:

• Deferoxamine, which has been the major iron-chelating treatment for transfusional iron overload 5.
• Deferiprone, which has been shown to be effective in reducing serum ferritin levels and decreasing cardiac and liver iron content 7, 6.
• Deferasirox, which offers an important treatment option for people with thalassemia and secondary iron overload 7.
• Combination therapy with multiple iron chelators, which may improve iron chelation and reduce the risk of complications 7, 6.