Hypoxia Biomarkers, Oxidative Stress, and Circulating Microparticles in Pediatric Patients With Thalassemia in Upper Egypt

Abstract

This study aimed to investigate the oxidative stress, hypoxia biomarkers, and circulating microparticles (MPs) in β thalassemia major. The study included 56 children with thalassemia and 46 healthy controls. Hypoxia biomarkers, oxidative stress biomarkers, and total plasma fragmented DNA (fDNA) were detected by the standard methods. The MPs were assessed by flow cytometry. Hypoxia and oxidative stress biomarkers, fDNA, and MPs were higher and total antioxidant capacity (TAC) was lower in patients with thalassemia than the controls. In splenectomized patients and those who had complications, vascular endothelial growth factor (VEGF), malondialdehyde, fDNA, endothelial, platelet, and activated platelet MP levels were higher while, TAC was lower than the nonsplenectomized patients. In conclusion, the increased tissue hypoxia, oxidative stress in β thalassemia, and its relationship with DNA damage and MPs release could explain many complications of thalassemia and may have therapeutic implications. The VEGF could serve as an important indicator for adequacy of blood transfusion in thalassemia.

Extracellular Vesicle Characteristics in β-thalassemia as Potential Biomarkers for Spleen Functional Status and Ineffective Erythropoiesis

“…RBC in TDT patients are mostly transfused erythrocytes, and RBC MPs originate only in small part from thalassemic erythropoiesis (Agouti et al, 2015). Previous studies in TDT patients have found higher levels of MPs originated from RBC and platelets than in controls (Tantawy et al, 2013; Agouti et al, 2015), most notably in splenectomized patients (Elsayh et al, 2014). The lower amount of RBC EVs found in our study can be explained by the patients’ reduced RBC count, despite receiving regular blood transfusions, and the existence of patients with hypersplenism in the patients’ cohort.…”

“…In line with our results from NTA, the Hy patients had the lowest EV concentrations. Previous studies have demonstrated significantly increased levels of MPs in both NTDT (Pattanapanyasat et al, 2007; Westerman et al, 2008; Chaichompoo et al, 2012) and TDT patients, with higher levels in the splenectomized vs. non-splenectomized patients (Tantawy et al, 2013; Elsayh et al, 2014; Agouti et al, 2015). Only a small fraction, approximately 5% of the large EV population (≥300 nm), can be measured by flow cytometry to identify membrane antigens and external membrane exposure of negatively charged phospholipids, mainly PS.…”

“…After splenectomy, blood cell counts and circulating MPs increase. This has been observed in patients with immune thrombocytopenia (Fontana et al, 2008; Sewify et al, 2013), β-thalassemia intermedia (β-TI) patients (Pattanapanyasat et al, 2007; Habib et al, 2008; Westerman et al, 2008; Klaihmon et al, 2017) and TDT patients; in the latter group, splenectomy has been associated with higher levels of MPs (Tantawy et al, 2013; Elsayh et al, 2014; Agouti et al, 2015) and increased procoagulant activity of platelet MPs (Agouti et al, 2015). However, there have been no studies characterizing EVs in thalassemic patients with hypersplenism.…”

“…Previous studies in patients with β-thalassemia have demonstrated increased levels of MPs in both NTDT (Pattanapanyasat et al, 2007; Westerman et al, 2008; Chaichompoo et al, 2012) and in TDT; in addition with a higher number of MPs originated from RBCs and platelets (Tantawy et al, 2013; Elsayh et al, 2014; Agouti et al, 2015). After splenectomy, blood cell counts and circulating MPs increase.…”

Quantitative proteomics of plasma vesicles identify novel biomarkers for hemoglobin E/β-thalassemic patients

“…Several factors play a role here, such as incomplete (b 1 ) or complete (b 0 ) loss of the b-globin chain, association with hereditary persistence of fetal hemoglobin, the degree of disparity between a-and non-a-globin chains, the starting onset and requirement for blood transfusion therapy, 4 and also extracellular vesicle (EV) production. 5,6 The numbers of EVs observed in the plasma of thalassemic patients are 4 times higher than in healthy controls; these are thought to be generated from the severe oxidative stress exposure of thalassemic red cells 7 and are also derived from platelets. 8 It is well established that these EVs are associated with increased clinically significant procoagulant activity.…”