Iron deficiency anemia and platelet dysfunction: A comprehensive analysis of the underlying mechanisms

Aims: This research aimed to study the changes in platelet function and their underlying mechanisms in iron deficiency anemia. Main methods: Initially, we evaluated platelet function in an IDA mice model. Due to the inability to accurately reduce intracellular Fe2+ concentrations, we investigated the impact of Fe2+ on platelet function by introducing varying concentrations of Fe2+. To probe the underlying mechanism, we simultaneously examined the dynamics of calcium in the cytosol, and integrin alpha IIb beta 3 activation in Fe2+-treated platelets. Ferroptosis inhibitors Lip-1 and Fer-1 were applied to determine whether ferroptosis was involved in this process. Key findings: Our study revealed that platelet function was suppressed in IDA mice. Fe2+ concentrationdependently facilitated platelet activation and function in vitro. Mechanistically, Fe2+ promoted calcium mobilization, integrin alpha IIb beta 3 activation, and its downstream outside-in signaling. Additionally, we also demonstrated that ferroptosis might play a role in this process. Significance: Our data suggest an association between iron and platelet activation, with iron deficiency resulting in impaired platelet function, while high concentrations of Fe2+ contribute to platelet activation and function by promoting calcium mobilization, alpha IIb beta 3 activation, and ferroptosis.