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Transfusion-Dependent Thalassemia: Iron Overload And Organ Dysfunction

Transfusion-Dependent Thalassemia: Iron Overload And Organ Dysfunction

Transfusion-dependent thalassemia (TDT) is an inherited blood disorder found most often in the Middle East and Africa. In places like Iran, beta-thalassemia, a more common type, has major and minor subtypes. The severe form, called Cooley’s anemia, lacks beta protein in hemoglobin, making regular blood transfusions necessary for survival. Complications linked with beta-thalassemia include issues like too much iron in the body, an enlarged spleen, growth problems, immune system troubles, heart and kidney failure, and liver disease.

The big worry for TDT patients is iron overload, which can lead to serious problems like hormone issues, heart troubles, diabetes, hearing problems, fragile bones, and stunted growth. This happens because the body absorbs more iron than it should due to the increased production of red blood cells, leading to a buildup in different organs. TDT patients are especially vulnerable to this, with iron levels in their bodies reaching as high as 200 mg per unit, compared to the annual absorption of about 0.05 g in healthy individuals.

Too much iron messes with the body’s balance, raising the levels of iron outside cells and within them. This excess iron produces harmful substances that damage cells, potentially causing heart and kidney issues, immune system problems, growth challenges, and liver disease. In places with limited resources, treating major thalassemia often involves regular blood transfusions along with iron-chelating medications like Deferoxamine, L1, and Deferasirox (DFX). However, keeping an eye on ferritin levels in the blood is crucial to prevent iron overload and its related complications.

The Study 

Thalassemia syndrome, a widespread hemoglobinopathy observed globally, represents a notable health challenge characterized by abnormalities in the production of hemoglobin. This condition, often requiring regular blood transfusions, is further compounded by the accumulation of excessive iron in the body, adding an additional layer of complexity to its management.

The significance of this health concern becomes even more apparent when considering the potential consequences of elevated ferritin levels in individuals grappling with transfusion-dependent beta-thalassemia. Ferritin, a protein that stores iron, assumes a crucial role in iron regulation. When its levels become heightened, as is often the case in thalassemia patients due to repeated blood transfusions, it sets the stage for severe implications on various organs within the body.

This study, undertaken with the intent of unraveling the intricacies of iron overload in individuals with transfusion-dependent beta-thalassemia, aims to shed light on the adverse effects this condition may have on vital bodily organs. By delving into the intricate interplay between heightened iron levels and the functioning of organs, the research seeks to provide valuable insights into the potential risks and complications associated with thalassemia-related iron overload.

The adverse effects of iron overload are far-reaching, impacting crucial organs such as the heart, liver, and endocrine system. The accumulation of excess iron within these organs can lead to a cascade of complications, ranging from cardiomyopathy and liver dysfunction to endocrine disorders. Understanding the nuanced relationship between iron overload and its consequences is essential for developing targeted interventions and treatment strategies to mitigate the potential harm caused by this intricate interplay.

In essence, this study stands as a pivotal endeavor in the broader context of thalassemia research, aiming not only to deepen our comprehension of the complexities associated with iron overload but also to pave the way for more effective and personalized approaches in the management of transfusion-dependent beta-thalassemia.


A comprehensive study was conducted on 1010 individuals diagnosed with transfusion-dependent beta-thalassemia at medical centers in Tehran, Iran. The primary objective was to investigate the correlation between iron overload and complications in vital organs. Blood samples were randomly collected from the participants, accompanied by a questionnaire to gather demographic and clinical information, including age, gender, thalassemia type, and chelator medication doses.

Various diagnostic procedures were employed, such as audiometric tests, hematologic and blood analyses (complete blood count and ferritin level), echocardiography measuring pulmonary artery pressure (PAP) and ejection fraction (EF), and bone densitometry. Additionally, dynamic MRI was used to measure hepatic and cardiac iron concentrations. The participants were categorized based on age and gender (under 20 years and over 20 years) to explore the effects of iron overload on crucial organs like the heart, liver, and endocrine system. Spleen removal surgery was performed on patients requiring transfusions over 240 mL/kg/year or experiencing hypersplenism.

All examinations adhered to ethical standards, with the study conducted under the ethical code (IR. IUMS. REC. REC.1396.30247) certified by the ethical committee of the Iran University of Medical Sciences. The study spanned from January 2015 to December 2022.


In this comprehensive investigation involving 1010 participants, the demographic composition was diverse, with 497 individuals (49%) being male and 513 (51%) female, representing a broad age range from 5 to 74 years. A noteworthy majority of the participants, constituting 85%, were aged over 20 years, contributing to a robust and varied dataset.

The study meticulously examined the relationship between elevated ferritin levels and various factors. Surprisingly, the analysis indicated that there was no significant correlation between elevated ferritin levels and key parameters such as sex, cholesterol levels, low-density lipoprotein, parathyroid hormone, T4, and aspartate aminotransferase. 

This suggests that the impact of elevated ferritin levels does not exhibit a clear association with these particular factors in the studied population. The findings underscore the complexity of the interplay between ferritin levels and these specific variables, emphasizing the need for further exploration and understanding in this area of research.

However, increasing ferritin levels exhibited notable associations with elevated triglyceride, phosphorus, thyroid-stimulating hormone, alkaline phosphatase, alanine transaminase, and pulmonary artery pressure (PAP) levels, as well as with age, hearing disorders, splenectomy, osteoporosis. Additionally, there were correlations with decreased high-density lipoprotein, body mass index, calcium, and ejection fraction (EF) levels.


Final Thoughts 

The improvements in both survival rates and the overall quality of life for individuals grappling with beta-thalassemia can be directly linked to the adoption of a multidisciplinary care model within a comprehensive healthcare unit. This pioneering approach is marked by continuous follow-up and the proactive identification of potential complications, embodying a commitment to the ongoing well-being of patients.

In this collaborative healthcare paradigm, a diverse team of medical professionals comes together, each contributing their specialized expertise. Hematologists, with their in-depth knowledge of blood disorders, work in tandem with nurses, nutritionists, and other specialists to create a well-rounded support system. This collaborative effort is pivotal in delivering holistic and personalized care tailored to the unique needs of each patient.

The hematologists contribute their expertise in understanding and managing blood disorders, while nurses play a vital role in patient care, ensuring adherence to treatment plans and facilitating communication between patients and the broader healthcare team. Nutritionists bring their insights into dietary considerations, an essential aspect of managing thalassemia effectively. The combined efforts of this multidisciplinary team not only address immediate medical concerns but also focus on the broader aspects of a patient’s life, contributing to an enhanced quality of life and an improved prognosis.

This approach goes beyond treating the symptoms of beta-thalassemia; it embraces a holistic perspective that recognizes the interconnectedness of various aspects of health and well-being. By fostering a collaborative and comprehensive healthcare environment, multidisciplinary care stands as a cornerstone in the ongoing efforts to provide the best possible outcomes for individuals facing the challenges of beta-thalassemia.

Through regular check-ups, proactive monitoring, and the prompt identification of emerging complications, this multidisciplinary care model aims to optimize treatment outcomes, mitigate potential health issues, and contribute to an overall improvement in the well-being of beta-thalassemia patients.

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