Iron Chelation Therapy in Hemoglobin Disorders

Hemoglobin disorders such as β-thalassaemia major and sickle cell disease often necessitate regular red‐cell transfusions to maintain adequate oxygen delivery. Over time, repeated transfusions lead to pathological iron accumulation in vital organs, notably the liver, heart and endocrine glands, driving complications that include cardiomyopathy, hepatic fibrosis and endocrinopathies. Iron chelation therapy aims to mobilise and excrete excess iron while preserving adequate systemic iron for erythropoiesis. Three main chelators—deferoxamine, deferiprone and deferasirox—differ in route of administration, iron‐binding affinity and tissue penetration. Deferoxamine, administered parenterally, remains effective but is limited by poor compliance and local complications. Oral chelators have transformed long-term management by improving adherence and enabling tailored regimens. Combination strategies leverage complementary pharmacodynamics to enhance cardiac iron clearance and reduce organ‐specific toxicity. Non-invasive monitoring using serum ferritin, transferrin saturation and magnetic resonance imaging (T2* measurement) guides dose adjustments and prevents both under- and over-chelation. Emerging approaches focus on early intervention to prevent toxic iron species from forming, and on precision medicine to mitigate adverse events. Despite significant gains in survival and quality of life, challenges persist in optimising chelation across diverse patient populations and healthcare settings.

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Iron Chelation Therapy in Hemoglobin Disorders publication trend

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Technical terms

Serum ferritin: Intracellular protein whose circulating concentration reflects total body iron stores.

Transferrin saturation: Percentage of iron-binding sites on transferrin occupied by iron, indicating circulating iron load.

Non-transferrin-bound iron (NTBI): Labile plasma iron not bound to transferrin, implicated in oxidative tissue damage.

Cardiac T2*: Magnetic resonance measurement inversely related to myocardial iron concentration.

Deferoxamine: Parenteral iron chelator that binds excess iron for renal and faecal excretion.

Deferiprone: Oral chelator capable of shuttling iron to transferrin and penetrating myocardial tissue.

Deferasirox: Once-daily oral chelator that binds ferric iron for elimination primarily via the bile.

References

1. Efficacy and safety of early‐start deferiprone in infants and young children with transfusion‐dependent beta thalassemia: Evidence for iron shuttling to transferrin in a randomized, double‐blind, placebo‐controlled, clinical trial (START). American Journal of Hematology (2023).
2. Case report: Acute liver failure during deferasirox therapy and the potential role of pharmacogenetics. Frontiers in Pharmacology (2024).
3. Iron Chelators in Treatment of Iron Overload. Journal of Toxicology (2022).