Cardioprotection by Deferiprone[L1] Inspite of Rising Serum Ferritin in Beta Thalassemia Major Patients.
Authors: Pathare Anil , Daar Shahina , Alkindi Salam , Dennison J.David 
Published: April 2020

Abstract
Background: Iron overload is the main cause of morbidity and mortality especially from heart failure in patients with beta thalassemia major (TM). Successful iron chelation is therefore essential for the optimal management of TM. Although desferrioxamine (DFX) has been the major iron-chelating treatment of transfusional iron overload, compliance is a major hindrance in achieving optimal therapeutic results. The availability of oral iron chelation with deferiprone (L1) is useful but shows poor efficacy when used alone as compared to DFX. We observed that inspite of rising serum ferritin, these patients benefit by an improvement in the myocardial performance parameters indicating a cardioprotective effect of L1 inspite of worsening of transfusional iron overload.
Aim: To study the cardioprotective efficacy of L1 in a prospective study over one year in beta thalassemia major patients with transfusional overload by echocardiography.
Methods: We studied 23 patients [M:F;12:11] with beta thalassemia major (Mean age + SD, 19.48 + 5.02; Range 13–32 years) attending the Day Care unit for regular transfusional support. They received packed red cells every 3–4 weeks to maintain pre-transfusion hemoglobin concentration above 9 g/dl. They had been receiving DFX at a daily dose of 40mg/kg/day by subcutaneous infusion for 8–10 hrs on 4–5 nights each week for past several years. However, due to various reasons, they had developed considerable transfusional iron overload and could not continue to use DFX owing to poor compliance. These patients were allocated to prospectively receive therapy with oral iron chelator L1 [Deferiprox-APOTEX] at 75mg/kg body weight in three divided doses with food after informed consent. They were observed and examined regularly at monthly intervals when they came for regular blood transfusions. Cardiac evaluation was performed with a yearly assessment of ECG and echocardiography. Iron overload assessment was performed by serial serum ferritin levels every two months. It being an acute phase reactant, ESR and C-reactive protein were also estimated whenever needed to validate the utility of ferritin levels as a marker of iron overload.
Results: Over the one year study period, the mean serum ferritin rose dramatically from 5209 ng/ml to 6792 ng/ml (p&lt;0.004;paired t test). Interestingly, over the same period there was a significant improvement in the myocardial function as assessed by the Ejection fraction which improved from 68.22% to 73.87% (p&lt;0.0001) and Fractional shortening which also rose from 33.45% to 37.44% (p&lt;0.0001).
Improved myocardial performance inspite of progressive worsening of iron overload with Deferiprone therapy for one year[n=23] SF Pre L 1 SF After one year EF Pre L 1 EF After one year FS Pre L 1 FS After one year SF-Serum Ferritin ng/ml;EF-Ejection Fraction%;FS-Fractional Shortening% Mean 5209 6791 68.22 73.87 33.45 37.45 ±SD 2638 4271 5.3 4.8 4.06 4.42 Range - Min 2006 3395 58 62 25.2 29.9 Range - Max 14000 20000 75 88 42 51.1 Students paired ‘t’ test p&lt;0.004 p&lt;0.0001 p&lt;0.0001
Summary/Conclusion: The study emphasizes that beta thalassemia major patients with transfusional iron overload who receive L1 at 75 mg/kg/day as their main chelation therapy show progressive iron overloading. However, inspite of this there is a silver lining is as much as that this treatment has a significant cardio protective effect as shown by the improvement in the echocardiographic parameters of myocardial performance in these patients under study.