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 Fe 2+ concentrations, we investigated the impact of Fe 2+ on platelet function by introducing varying concentrations of Fe 2+ . To probe the underlying mechanism, we simultaneously examined the dynamics of calcium in the cytosol, and integrin αIIbβ3 activation in Fe 2+ -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. Fe 2+ concentration-dependently facilitated platelet activation and function in vitro. Mechanistically, Fe 2+ promoted calcium mobilization, integrin αIIbβ3 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 Fe 2+ contribute to platelet activation and function by promoting calcium mobilization, αIIbβ3 activation, and ferroptosis.