The Safety of Chelators for Iron Overload in Sickle Cell Disease: A Brief Systematic Review

Basseem Radwan,İ İpek Boşgelmez

doi:10.32552/2019.actamedica.368

Abstract

Sickle cell disease (SCD) is a group of disorders that affects hemoglobin due to a mutation of the hemoglobin beta gene (HBB) on chromosome 11. Patients with SCD have atypical hemoglobin molecules called hemoglobinS (HbS), which distort erythrocytes into a “sickle-shape”. Typical symptoms of SCD include periodic episodes of pain, repeated infections, and anemia. This disorder is abundant in sub-Saharan African countries, the Mediterranean region, and also appears in some southern provinces in Turkey. Because of the high concentration of HbS in patients, a high risk of chronic anemia and vaso-occlusive events, such as stroke may deteriorate suddenly. In these conditions, transfusion of blood, especially erythrocytes, can be life-saving. However, chronic blood transfusions may lead to iron overload in SCD patients. Erythrocyte transfusion is associated with a higher risk in most patients with SCD than in the general population. Therefore, chelation therapy has become an important component of the transfusion program to prevent complications of iron accumulation in organs such as liver and heart. In this study, we sought to conduct a systematic review to assess the safety of iron chelating agents used by SCD patients with iron overload mainly due to necessary blood transfusion regime. Our evaluation revealed that in general iron chelation therapy, either deferasirox, deferoxamine or deferiprone, remains the most effective and safest available method to treat iron overload in SCD. Furthermore, current reports do not reflect any significant safety concerns against the use of available chelators.

Highlights

Sickle cell disease (SCD) is one of the most common serious inherited hemoglobinopathies around the world [1]
SCD can be described as a group of disorders that affects hemoglobin (Hb) because of a point mutation in hemoglobin beta gene (HBB) on chromosome 11 [4]
This change induces the formation of 50 hemoglobin S (HbS) instead of HbA, which causes red blood cell (RBC) to become sickle-shaped paving the way to a group of acute and chronic complications such as vaso-occlusive crisis (VOC), acute chest syndrome, pain episodes, and recurrent infections [5]

Summary

INTRODUCTION

Sickle cell disease (SCD) is one of the most common serious inherited hemoglobinopathies around the world [1]. Blood Transfusion and Iron Overload in SCD Because of high HbS concentrations, SCD patients are at increased risk of exposure to vaso-occlusive events which may suddenly deteriorate In these conditions, blood or especially RBC transfusion can be life-saving [17]. Our aim in the current systematic review was to evaluate the safety profiles of DFO, DFP, and DFX in the treatment of iron overload in SCD To achieve this goal, we searched for relevant clinical studies in databases and reviewed the most appropriate reports in view of adverse reactions, other unwanted or unexpected consequences. Studies that passed the abstract review phase were excluded from this systematic review based on the following exclusion criteria: theoretical papers (n= 9), absence of safety data (n= 7) or lack of Iron Chelation therapy (ICT) data (n= 1), the number of patients with SCD less than 20 (n= 6) or if it focused on hematopoietic stem cell transplant (HSCT) (n= 1). Among the trials included in this review, only one of these was conducted using DFP [30]

Design

Findings

CONCLUSION