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 αIIbβ3 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⁺ concentration-dependently facilitated platelet activation and function in vitro. Mechanistically, Fe²⁺ 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 Fe²⁺ contribute to platelet activation and function by promoting calcium mobilization, αIIbβ3 activation, and Ferroptosis.