A 7-year-old boy from Tamil Nadu with β-thalassemia major presents with severe anemia (Hb 5.2 g/dL) and hepatosplenomegaly. He has received multiple transfusions over the past 3 years. Which drug is the first-line choice to prevent iron overload complications in this patient?

Explanation

## Iron Chelation Therapy in Thalassemia Major **Key Point:** Deferasirox is the first-line iron chelator in thalassemia major due to superior efficacy, oral bioavailability, and patient compliance compared to older agents. ### Mechanism of Action Deferasirox is an oral tridentate iron chelator that binds ferric iron (Fe³⁺) with high affinity and allows urinary excretion. It achieves rapid and sustained reduction in labile plasma iron (LPI) and tissue iron burden. ### Comparison of Iron Chelators | Agent | Route | Onset | Efficacy | Compliance | Monitoring | |-------|-------|-------|----------|-----------|------------| | **Deferasirox** | Oral | Rapid (days) | Excellent | High | Renal function, LFTs | | Desferrioxamine | IV/SC | Slow (weeks) | Good | Poor (infusions) | Auditory, visual | | Deferriprone | Oral | Moderate | Good | Moderate | Agranulocytosis risk | | Penicillamine | Oral | Slow | Poor | Moderate | Multiple toxicities | **High-Yield:** Deferasirox is preferred as **first-line** in newly transfused thalassemia patients because: - Once-daily oral dosing (500–2000 mg) - Rapid reduction in serum ferritin - No need for infusion pumps or injections - Better long-term cardiac and hepatic outcomes ### Clinical Pearl Iron overload in thalassemia leads to: 1. **Cardiac:** arrhythmias, dilated cardiomyopathy (leading cause of death) 2. **Hepatic:** cirrhosis, HCC 3. **Endocrine:** diabetes, hypogonadism, hypothyroidism 4. **Pituitary:** growth hormone deficiency Chelation should begin after 10–20 transfusions or when serum ferritin exceeds 1000 ng/mL. ### Dosing & Monitoring - **Initial dose:** 20–30 mg/kg once daily - **Adjust:** based on serum ferritin trend - **Monitor:** serum creatinine, eGFR, LFTs, auditory/visual function (less common than with desferrioxamine) **Tip:** Deferasirox can be combined with deferriprone in severe iron overload, but deferasirox monotherapy is standard first-line. [cite:Robbins 10e Ch 14]