Novel Approach to Reactive Oxygen Species in Nontransfusion-Dependent Thalassemia

Abstract

The term Nontransfusion dependent thalassaemia (NTDT) was suggested to describe patients who had clinical manifestations that are too severe to be termed minor yet too mild to be termed major. Those patients are not entirely dependent on transfusions for survival. If left untreated, three main factors are responsible for the clinical sequelae of NTDT: ineffective erythropoiesis, chronic hemolytic anemia, and iron overload. Reactive oxygen species (ROS) generation in NTDT patients is caused by 2 major mechanisms. The first one is chronic hypoxia resulting from chronic anemia and ineffective erythropoiesis leading to mitochondrial damage and the second is iron overload also due to chronic anemia and tissue hypoxia leading to increase intestinal iron absorption in thalassemic patients. Oxidative damage by reactive oxygen species (generated by free globin chains and labile plasma iron) is believed to be one of the main contributors to cell injury, tissue damage, and hypercoagulability in patients with thalassemia. Independently increased ROS has been linked to a myriad of pathological outcomes such as leg ulcers, decreased wound healing, pulmonary hypertension, silent brain infarcts, and increased thrombosis to count a few. Interestingly many of those complications overlap with those found in NTDT patients.

Mean Platelet Volume in Heterozygous Beta Thalassaemia

“…As the factor causing coagulation activation in HBT is mild haemolysis, it could be that this is overcome by congenital or acquired platelet dysfunction, and thrombotic events may occur less frequently in patients with HBT compared to in the general population [2,14,26]. These pathophysiologic mechanisms are very likely also applicable for increased incidence of thrombosis in beta thalassaemia intermedia [28,29]. Despite the platelet dysfunction observed in patients with sickle-cell anaemia by Gruppo et al [13], the paradoxically increased thrombosis in these patients may be explained by the abovementioned mechanisms [30,31].…”

Protective effects of GABA against metabolic and reproductive disturbances in letrozole induced polycystic ovarian syndrome in rats

“…Glutathione reductase (GSR) activity was determined by the method of [ 19 ]. Reactive oxygen species (ROS) activity was determined by following method of [ 20 ]. Reduced glutathione (GSH) activity was determined by following method of [ 21 ] with some modifications by utilizing Ellman’s reagent (DTNB).…”

Elevations of Thrombotic Biomarkers in Hemoglobin H Disease

“…This destroys membrane rigidity easily by the reticuloendothelial system. Degraded RBCs release ferric ion and non-transferrin-bound iron, which can react with oxygen atoms to generate reactive oxygen species (ROS) [22]. ROS can oxidize endothelium and red cell membranes that expose PS from inner to outer cells followed by triggered blood coagulation.…”

“…Increased ICAM-1 levels, a marker of endothelial injury, were generated by ROS from free β-globlin chains or labile plasma iron [22, 25]. Serum ferritin level >1,000 μg/L is a biomarker for monitoring iron overload [26].…”