Sickle cell disease: role of oxidative stress and antioxidant therapy

Sickle cell disease (SCD) is the most common hereditary disorder of hemoglobin (Hb), which affects approximately a million people worldwide. It is characterized by a single nucleotide substitution in the β-globin gene, leading to the production of abnormal sickle hemoglobin (HbS) with multi-system consequences. HbS polymerization is the primary event in SCD. Repeated polymerization and depolymerization of Hb causes oxidative stress that plays a key role in the pathophysiology of hemolysis, vessel occlusion and the following organ damage in sickle cell patients. For this reason, reactive oxidizing species and the (end)-products of their oxidative reactions have been proposed as markers of both tissue pro-oxidant status and disease severity. Although more studies are needed to clarify their role, antioxidant agents have been shown to be effective in reducing pathological consequences of the disease by preventing oxidative damage in SCD, i.e., by decreasing the oxidant formation or repairing the induced damage. An improved understanding of oxidative stress will lead to targeted antioxidant therapies that should prevent or delay the development of organ complications in this patient population

Association of heterocellular HPFH, β+-thalassaemia, and δβ° -thallassaemia: Haematological and molecular aspects

An Italian family in which heterocellular hereditary persistence of fetal haemoglobin (HPFH) interacts with both β+- and δβ-thalassaemia is described. The index case was an 8 year old girl who was presumed to inherit both heterocellular HPFH and β+-thalassaemia from her mother and δβ-thalassaemia from her father. She was healthy and never needed blood transfusions. The possible contribution of heterocellular HPFH to the less severe expression of the compound δβ/β+-thalassaemia heterozygosity is discussed. By DNA analysis the specific δβ-thalassaemia defect on the γδβ globin gene region has been established. In addition, a previously unreported association of a polymorphic restriction site haplotype with a β+-thalassaemia mutation has been observed