The role of anaemia in oxidative and genotoxic damage in transfused β-thalassaemic patients

Objectives: Redox imbalance and genotoxic damage are commonly observed in beta thalassaemic patients. The aim of this study was to assess the role of anaemia in oxidative and genotoxic damage in regularly transfused thalassaemic patients, undergoing iron chelation therapy. Methods: We studied the relationships of haematological, biochemical and clinical parameters with oxidative (reactive oxygen species and 8-oxo-7,8-dihydro-2'-deoxyguanosine) and genotoxic biomarkers (Comet assay and cytokinesis-block micronucleus test) in blood samples from 105 patients. To reduce the early effect of redox-active iron, samples were collected when pharmacokinetics of the iron chelators ensured their maximum effectiveness. The transfusion regimen, cardiac and hepatic magnetic resonance imaging T2* were evaluated to characterize the patient cohort. Labile plasma iron (LPI) was also assayed. Results: Haemoglobin level had a significant effect on ROS, % DNA in the tail and micronuclei-micronucleated cell frequency (p < 0.05). Higher Hb values reduced redox imbalance. LPI, detectable in 50.5% of patients, was related to the number of apoptotic and necrotic lymphocytes (p = 0.03), demonstrating the cytotoxic effect of iron. Discussion: The results highlight that an adequate transfusion regimen is essential to limit oxidative and genotoxic damage in beta-thalassemic patients undergoing chelation therapy. Conclusion: Owing to the higher risk of cancer in the thalassaemic cohorts, specific genotoxicity/oxidative biomarkers should be monitored in order to ameliorate and formulate more personalized disease management.