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Abnormal red blood cell morphological changes in thalassaemia associated with iron overload and oxidative stress
  1. Pornthip Chaichompoo1,
  2. Ariz Qillah1,
  3. Pornpan Sirankapracha2,
  4. Jirada Kaewchuchuen3,
  5. Poramate Rimthong4,
  6. Kittiphong Paiboonsukwong2,
  7. Suthat Fucharoen2,
  8. Saovaros Svasti2,5,
  9. Suchin Worawichawong4
  1. 1 Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand
  2. 2 Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
  3. 3 Department of Pharmacology, Faculty of Science, Mahidol University, Bangkok, Thailand
  4. 4 Electron Microscopy Unit, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
  5. 5 Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok, Thailand
  1. Correspondence to Dr Pornthip Chaichompoo, Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand; pornthip.chh{at}mahidol.ac.th

Abstract

Aims Iron overload is a major factor contributing to the overall pathology of thalassaemia, which is primarily mediated by ineffective erythropoiesis and shorter mature red blood cell (RBC) survival. Iron accumulation in RBCs generates reactive oxygen species (ROS) that cause cellular damage such as lipid peroxidation and RBC membrane deformation. Abnormal RBCs in patients with thalassaemia are commonly known as microcytic hypochromic anaemia with poikilocytosis. However, iron and ROS accumulation in RBCs as related to RBC morphological changes in patients with thalassaemia has not been reported.

Methods Twenty-one patients with thalassaemia, including HbH, HbH with Hb Constant Spring and β-thalassaemia/HbE (splenectomy and non-splenectomy) genotypes, and five normal subjects were recruited. RBC morphology was analysed by light and scanning electron microscopy. Systemic and RBC iron status and oxidative stress were examined.

Results Decreased normocytes were observed in the samples of patients with thalassaemia, with RBC morphological abnormality being related to the type of disease (α-thalassaemia or β-thalassaemia) and splenic status. Target cells and crenated cells were mainly found in splenectomised patients with β-thalassaemia/HbE, while target cells and teardrop cells were found in non-splenectomised patients. Patients with thalassaemia had high levels of serum ferritin, red cell ferritin and ROS in RBCs compared with normal subjects (p<0.05). Negative correlations between the amount of normocytes and serum ferritin (rs=−0.518, p=0.011), red cell ferritin (rs=−0.467, p=0.025) or ROS in RBCs (rs=−0.672, p<0.001) were observed.

Conclusions Iron overload and its consequent intracellular oxidative stress in RBCs were associated with reduce normocytes in patients with thalassaemia.

  • thalassemia
  • red cell morphology
  • iron overload
  • oxidative stress
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Footnotes

  • Handling editor Mary Frances McMullin.

  • Contributors PC was the principal investigator and takes primary responsibility for the concept and design of the project, performed flow cytometry, analysis of data and drafting the manuscript. AQ was responsible for sample preparation and capture of images from the light microscope. AQ and PR performed sample preparation and image capture from the scanning electron microscope. PS performed determination of serum ferritin and red cell ferritin. JK performed determination of plasma isoprostane. KP and SF contributed to specimen collection. SS and SW contributed to the concept of the study, design of the experiments, analysis of the data and drafting the manuscript. All authors reviewed and approved the final version to be published.

  • Funding This work was supported by the Faculty of Science and the Faculty of Medicine Ramathibodi Hospital, Mahidol University; Mahidol University Research Grants and Bilateral Programs; Japan Society for the Promotion of Science (JSPS); and the National Research Council of Thailand (NRCT).

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was performed in accordance with the Helsinki Declaration and was approved by the Mahidol University Central Institutional Review Board (MU-CIRB) (approval number COA.No.2015/076.1906). Written informed consent was obtained from all individual participants included in the study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement No data are available.

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