Cardiac complications in thalassemia throughout the lifespan: Victories and challenges

Abstract

Thalassemias are among the most common hereditary diseases in the world because heterozygosity offers protection against malarial infection. Affected individuals have variable expression of alpha or beta chains that lead to their unbalanced utilization during hemoglobin formation, oxidative stress, and apoptosis of red cell precursors prior to maturation. Some individuals produce sufficient hemoglobin to survive but suffer the vascular stress imposed by chronic anemia and ineffective erythropoiesis. In other patients, mature red cell formation is insufficient, and chronic transfusions are required—suppressing anemia and ineffective erythropoiesis but at the expense of iron overload. The cardiovascular consequences of thalassemia have changed dramatically over the previous five decades because of evolving treatment practices. This review summarizes this evolution, focusing on complications and management pertinent to modern patient cohorts.

Ferroptosis as an emerging target in sickle cell disease

“…( Schmidt et al, 2021 , Schmidt et al, 2023 ). This is mirrored in conditions like thalassemia and hereditary hemochromatosis ( Wang et al, 2017 , Ginwalla et al, 2018 , Sumneang et al, 2020 , Fujikura et al, 2022 , Wood, 2023 ), as well as in myocardial infarction, reperfusion injuries, and heart failure ( Fang et al, 2023 , Wang et al, 2023a ), highlighting a pattern of cardiac iron toxicity.…”

“…Liver iron concentration (LIC), which closely correlates with total body iron, can be measured through liver biopsy or noninvasive methods like biomagnetometry or superconducting quantum interference device (SQUID) ( Kontoghiorghes, 2023 ), which can be also applied to spleen ( Bruzzese et al, 2023 ). However, these methods, while effective in quantifying hepatic iron overload, do not evaluate liver inflammation or fibrosis ( Wood, 2023 ). Magnetic Resonance Imaging (MRI) on the other hand, offers a non-invasive approach to assess the three-dimensional distribution of excess iron in the body.…”

Oxidative Stress and Antioxidant Status in Adult Patients with Transfusion-Dependent Thalassemia: Correlation with Demographic, Laboratory, and Clinical Biomarkers

“…Despite the advancements in iron chelation, secondary iron overload is still a major issue in β-TDT [17]. Consequently, β-TDT patients may incur in oxidative stress with overproduction of reactive oxygen species (ROS), which can lead to growth lag, delayed sexual development, and adverse consequences also for liver, heart, and endocrine system functioning [18,19]. Moreover, an elevated oxidative stress, which results from a shift in the balance between ROS and the antioxidant defense system, has been demonstrated as a key determinant in the pathogenesis of different chronic-degenerative diseases related to aging, including cardiovascular disease and Type 2 diabetes [20], which represent the more frequent and critical complications in β-TDT patients [21][22][23].…”