Introduction

Beta-thalassemia is an autosomal recessive hematological disorder prevalent in the Mediterranean area due to defects in the synthesis of β chains of hemoglobin, caused by a mutation in the HBB gene on chromosome 11 leading from asymptomatic to clinically severe hypochromic microcytic anemia [1].

The types of beta-thalassemia are major, intermedia, and minor depending on hemoglobin type and clinical presentations that include splenomegaly, hemolytic anemia, jaundice, and gallstones, those only seen in major and intermedia types, while in beta-thalassemia minor the clinical presentation is mainly misdiagnosed as iron deficiency anemia that was refractory to iron therapy [2].

Beta-thalassemia minor is treated with folic acid only and rarely needs a blood transfusion, while beta-thalassemia major and intermedia are blood transfusion-dependent types since untreated beta-thalassemia leads to congestive heart failure and eventually death [3]. Repeated blood transfusions lead to iron overload and toxicity causing cardiac siderosis, pulmonary hypertension, and endocrinopathy [4].

Therefore, iron chelating therapy is mandatory to prevent iron overload-induced complications accordingly, iron chelators such as deferoxamine, deferiprone, and deferasirox are used with repeated blood transfusion in the management of anemia in beta-thalassemia major and intermedia [5]. The first iron chelator was deferoxamine derived from Streptomyces pilosus which was introduced in 1960, administrated parenterally (intravenous [IV] or subcutaneous [SC] but not intramuscular) with a short half-life and dose-dependent effect [6].

SC administration of deferoxamine leads to severe pain at the site of injection, while prolonged IV administration leads to noncompliance; also, frequent deferoxamine administration causes growth retardation [7], thus, the necessity for oral iron chelator is required like deferiprone and deferasirox. Deferiprone is the first oral iron chelator, and it is a bidentate hydroxypyridone introduced in the year 1980 for the management of iron overload through binding with iron and the complex will excreted in the urine [8];

Group (A): 42 patients (22 females + 20 males) were treated with blood transfusion plus IV deferoxamine infusion (8 h/day) 30 mg/kg/every 3 days/week. Group (B): 58 patients (30 females + 28 males) were treated with blood transfusion plus oral deferasirox 30 mg/kg/day. Splenectomy had been achieved in 8 patients (5 males + 3 females) and the duration between splenectomy and participation in this study was 2–3 years.

Exclusion criteria included patients with sepsis, heart failure, renal failure, active liver disease and rheumatologic diseases.

Haematological parameters

A fasting blood sample of 10 mL was taken from an antecubital site from each patient and then centrifuged immediately; sera were stored at −80°C until used. Serum ferritin in ng/dL was assessed by a specific ELISA kit (Human Ferritin ELISA Simple Step ab200018).

Serum iron in μg/dL was estimated by a specific ELISA kit (serum iron ELISA Kit. ABIN2105464). Serum total iron binding in μg/dL was assessed by a specific ELISA kit (MBS2601224 Human Total iron-binding capacity ELISA Kit). All ELISA Kit methods were done according to the manufacturer's instructions.

Unsaturated iron-binding capacity (UIBC) which measures levels of free transferrin (not bound to iron), UIBC = Total iron-binding capacity (TIBC) (μg/Dl) − serum iron (μg/dL) [14]. A complete blood picture was prepared by Automated Touch Screen Hematology Analyzer, Hs Code: 90189090, China (WHY 6480).

Statistical analysis

Data were expressed as mean ± standard deviation, number and percentage. The unpaired Student's t-test was used to evaluate the significance of differences between the treated groups in terms of a 95% confidence interval, t value with P< 0.05 as statistically significant. Data analysis was done using SPSS (IBM SPSS Statistics for Windows, Version 26.0., 2023 Armonk, NY: IBM Corp).

Results

A total number of 100 patients with β-thalassemia aged 9.3 ± 2.5 years, female to male ratio was 1.08:1.

Table 2: The differences between the effect of deferoxamine and deferasirox on haematological parameters of blood transfusion-dependent β-thalassemia major or intermedia

*p<0.01, Data expressed as means+ SD, TIBC: Total iron binding capacity, SD: Standard deviation, CI: Confidence interval.

Discussion

This study revealed significant effects of deferasirox in reduction of iron overload in β-thalassemia compared to deferoxamine. In deferasirox-treated patients, serum ferritin levels were low compared to deferoxamine-treated patients due to higher efficacy and compliance of deferasirox [15], since; deferoxamine parenteral administration led to poor compliance and efficacy [16].

These findings correspond with the Vichinskyet al. study that showed higher efficacy of deferasirox compared to deferoxamine in the reduction of iron overload in hemolytic anemia [17]. In addition, animal model studies demonstrated the effectiveness of deferasirox in the reduction of liver and heart iron overloads more than deferiprone and deferoxamine [18].

Regarding patients that are treated with deferasirox, TIBC is improved through the reduction of serum iron and iron burden in transfusion-dependent β-thalassemia, since circulating iron is normally bound to transferrin but in a state of iron overload, the capacity for iron binding will be reduced leading to increase in the nontransferrin bound iron.

Consequently, this will lead to the induction of oxidative stress and reduction in the antioxidant capacity, so a high free iron can be taken by cardiac and hepatic parenchyma independent of transferrin receptors causing parenchymal damage [19].

References