Abstract
Ferroptosis, an iron-dependent form of cell death, has emerged as clinically relevant in various settings. This chapter focuses on the current landscape of ferroptosis in the context of hemolytic disorders and the iron overload that can occur due to heightened erythropoietic drive and/or transfusions of red blood cells (RBCs). In hemolytic disorders, RBCs are typically destroyed at a faster rate than new RBCs can be generated by the bone marrow. Examples include various instances of anemia, hemoglobinuria, and methemoglobinemia. During active, ongoing hemolysis, iron is processed and recycled at a much higher rate than under normal conditions, creating opportunities to generate destructive free radicals and lipid peroxidation. Thus far, in the context of hemolysis and iron overload, ferroptosis has been studied in the settings of transfusions of storage-damaged RBCs, hemochromatosis, acute kidney injury, and hemorrhagic stroke. Given their clinical significance, continued research in hemolytic disorders has the potential to offer tremendous insight in terms of both understanding these disorders and developing potential therapies.
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This work was funded, in part, by NIH T32 AI106711 and F31 HL134284 (to LAY) and by NIH R01 HL115557 and R01 HL133049 (to SLS). The figures in this chapter were created using BioRender. LAY has no conflicts to report. SLS is on the Scientific Advisory Board of Hemanext, Inc. and is a Consultant to Tioma, Inc., neither role is relevant to the current contribution.
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Youssef, L.A., Spitalnik, S.L. (2019). Ferroptosis in Hemolytic Disorders. In: Tang, D. (eds) Ferroptosis in Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-030-26780-3_15
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