Treating thalassemia major-related iron overload: the role of deferiprone

Abstract

Over the last 20 years, management for thalassemia major has improved to the point where we predict that patients’ life expectancy will approach that of the normal population. These outcomes result from safer blood transfusions, the availability of three iron chelators, new imaging techniques that allow specific organ assessment of the degree of iron overload, and improvement in the treatment of hepatitis. In October 2011, the Food and Drug Administration licensed deferiprone, further increasing the available choices for iron chelation in the US. The ability to prescribe any of the three chelators as well as their combinations has led to more effective reduction of total body iron. The ability to determine the amount of iron in the liver and heart by magnetic resonance imaging allows the prescription of the most appropriate chelation regime for patients and to reconsider what our aims with respect to total body iron should be. Recent evidence from Europe has shown that by normalizing iron stores not only are new morbidities prevented but also reversal of many complications such as cardiac failure, hypothyroidism, hypogonadism, impaired glucose tolerance, and type 2 diabetes can occur, improving survival and patients’ quality of life. The most effective way to achieve normal iron stores seems to be with the combination of deferoxamine and deferiprone. Furthermore, outcomes should continue to improve in the future. Starting relative intensive chelation in younger children may prevent short stature and abnormal pubertal maturation as well as other iron-related morbidities. Also, further information should become available on the use of other combinations in chelation treatment, some of which have been used only in a very limited fashion to date. All these advances in management require absolute cooperation and understanding of parents, children, and, subsequently, the patients themselves. Only with such cooperation can normal long-term survival be achieved, as adherence to treatment is now likely the primary barrier to longevity.

Biochemical and histopathological effects of green tea nanoparticles in ironized mouse model

“…The short half-time of DFO reduces the effectiveness of the chemical agent(20). This medication binds iron with a ratio of 1:1 and is excreted through urine and feces(21). DFO will bind non transferrin binding iron (NTBI), which in turn would reduce ROS production due to reduced NTBI circulating in the blood(22).…”

Dual T‐type and L‐type calcium channel blocker exerts beneficial effects in attenuating cardiovascular dysfunction in iron‐overloaded thalassaemic mice

“…Group III (FE/DFX) mice were fed with deferasirox (DFX, Novartis Pharma Stein AG, Stein, Switzerland; 30 mg kg −1 day −1 ) in NSS via gavage feeding daily (Pennell et al 2010). Group IV (FE/DFP) mice were fed with deferiprone (DFP, ApoPharma USA, Inc, Rockville, MD, USA; 75 mg kg −1 day −1 ) in NSS via gavage feeding twice daily (Berdoukas et al 2012). Group V (FE/Efo) mice were injected S.C. with the dual TTCC and LTCC blocker efonidipine (Sigma-Aldrich, St. Louis, MO, USA; 4 mg kg −1 day −1 ) in 0.5% DMSO daily (Matsumura et al 1995).…”

Physiology and pathophysiology of iron in hemoglobin-associated diseases

“…The ability to noninvasively measure tissue iron in humans by magnetic resonance imaging (MRI), major breakthroughs in our understanding of the molecular physiology of iron regulation, and the availability of new iron chelating agents have resulted in a dramatic improvement in the survival of patients with severe iron overload [1, 2]. …”