Iron Overload and Chelation Therapy in Non-Transfusion Dependent Thalassemia

Abstract

Iron overload (IOL) due to increased intestinal iron absorption constitutes a major clinical problem in patients with non-transfusion-dependent thalassemia (NTDT), which is a cumulative process with advancing age. Current models for iron metabolism in patients with NTDT suggest that suppression of serum hepcidin leads to an increase in iron absorption and subsequent release of iron from the reticuloendothelial system, leading to depletion of macrophage iron, relatively low levels of serum ferritin, and liver iron loading. The consequences of IOL in patients with NTDT are multiple and multifactorial. Accurate and reliable methods of diagnosis and monitoring of body iron levels are essential, and the method of choice for measuring iron accumulation will depend on the patient’s needs and on the available facilities. Iron chelation therapy (ICT) remains the backbone of NTDT management and is one of the most effective and practical ways of decreasing morbidity and mortality. The aim of this review is to describe the mechanism of IOL in NTDT, and the clinical complications that can develop as a result, in addition to the current and future therapeutic options available for the management of IOL in NTDT.

Thalassemias: An Overview

“…Chronic anemia and ineffective erythropoiesis persist despite a relatively steady hemoglobin level with the result of increasing iron absorption from the gut through hepcidin suppression. This causes iron toxicity mainly to the liver while the heart remains relatively free of iron-related damage [ 35 , 36 , 37 ]. Iron overload with the increased circulation of NTBI leads to hepatocyte damage which progresses to fibrosis, presumably due to longer duration of exposure [ 38 ] and to hepatocellular carcinoma, which is more frequent in NTDT.…”

Bone marrow stromal cells from β-thalassemia patients have impaired hematopoietic supportive capacity

“…Mutations in the gene encoding for the human β-globin gene result in a reduction in or absence of the beta-globin chains, leading to the accumulation of unstable α-hemoglobin, which is responsible for the pathophysiology of the disorder (3–5). Conventional treatment of BT relies on chronic and regular blood transfusions in association with iron-chelation therapy (6, 7). However, complications caused by iron accumulation and hepcidin dysregulation due to expanded ineffective erythropoiesis still affect quality of life and represent a cause of death (8–12).…”

Quality of life in patients with β‐thalassemia: A prospective study of transfusion‐dependent and non‐transfusion‐dependent patients in Greece, Italy, Lebanon, and Thailand

“…3 The NTDT patients also experience significant impacts on their QoL due to their disease, often associated with iron overload and the difficulty of adhering to ICT. 4 As a result, health-related QoL has emerged as a key focus of comprehensive clinical care in patients with β-thalassemia. Understanding the degree of patient-perceived health impairment is essential to determine the burden of illness of β-thalassemia and to recommend suitable therapy.…”