Oxidation Status of β-Thalassemia Minor and Hb H Disease, and Its Association with Glycerol Lysis Time (GLT₅₀)

Abstract

β-Thalassemia (β-thal), especially β-thalassemia major (β-TM), is reported to be related to reactive oxygen species (ROS) and enhanced oxidation status. It is reflected by increased malondialdehyde (MDA), by membrane lipid peroxidation and decreased by the newly developed total antioxidant capacity (TAC). However, there is less evidence for β-thal minor and Hb H (β4) disease on its association with oxidation status. On the other hand, hemolysis by glycerol lysis time (GLT50) is invariably prolonged in thalassemia. The reason for the prolongation of GLT50 is not well understood. The aim of this study was to investigate the oxidation state in β-thal minor and Hb H disease and to find out the association of the oxidation with the prolongation of GLT50. Blood samples from 39 subjects (33 with β-thal minor, six with Hb H disease) were collected from individuals living in Japan. The clinical screening tests and molecular identification of the thalassemias were performed. Malondialdehyde and TAC were measured using spectrophotometric analyses. In β-thal minor and Hb H disease, the plasma MDA level was significantly elevated and the TAC reduced. A highly reversed correlation between MDA and TAC was noted. Their GLT50 levels were evidently prolonged, and the GLT50 has significant correlations with MDA and TAC. β-Thalassemia minor and mild Hb H disease are evidently in a milieu of reduced redox state, and GLT50 prolongation in β-thal minor and Hb H disease has a close correlation with the oxidation state, possibly by oxidative impairment of the membrane protein of the red cell.

Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor

“… 7 However, there are some reports about elevated oxidative stress in patients with th-minor associated with increased lipid peroxidation and decreased catalase activity. 20 , 21 But in th-minor the ferritin level is within normal limits and the anemia is usually not serious with Hb levels >9 mg/dL. 2 Eventually, the oxidative status is most likely less than th-major in th-minor.…”

Ischemia-modified albumin as a marker of vascular dysfunction and subclinical atherosclerosis in β-thalassemia major

“…It has also been demonstrated that such patients experience decreased antioxidant capacity and increased products of peroxidative damage [4]. Enhanced oxidation status in β-TM is reflected by increased malondialdehyde (MDA), as a result of excess α-chains in erythrocytes and erythroblasts being unstable and prone to denaturation and oxidation, peroxidation of tissues that leak MDA into the blood, as well as depleted antioxidant capacity lowering defense to oxidants [5,6]. Liver lipid peroxidation also increases leakage of ferritin into the circulation.…”

A Coincidental Discovery of a New Stable Variant (Hb Hachioji orHBB: c.187C>T) in a Patient with Chronic Hemolytic Anemia of Unexplained Origin

“…Hb Hachioji was not separated on IEF. In addition, his instability (isopropanol) test was negative, while GLT 50 , which is prolonged by oxidative stress in thalassemia and unstable hemoglobinopathies, was prolonged [10]. At first, it was thought that Hb Hachioji presented as a highly unstable variant, which in erythrocytes prematurely denatured and precipitated, resulting in Heinz body formation with no Hb Hachioji remaining.…”

“…Blood was taken by venipuncture with EDTA as an anticoagulant. The blood was subjected to routine hematological analysis and measurement of half glycerol lysis time GLT 50 [9,10]. Hb F was quantitated by cation exchange HPLC for HbA 1c (HPLC 723 G8 V R ; Tosoh, Tokyo, Japan).…”

“…The product (270 bp) was processed and subjected to sequencing analysis. Furthermore, in order to investigate the presence of glucose-6-phosphate dehydrogenase (G6PD) deficiency and P4.2 abnormalities (P4.2Nippon), the promoter area, 5 0 untranslated region (5 0 UTR), 13 exons, and 3 0 UTR of the G6PD gene and exon 3 of the P4.2 gene were studied by PCR and DNA sequencing using the primers described by Adhiyanto et al [10].…”