Molecular Mechanisms of Drug-Induced Hemolysis in G6PD Deficiency: Mechanistic Insights

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a prevalent enzymopathy, predisposes individuals to hemolytic anemia upon exposure to various medications. This literature review explores the molecular underpinnings of drug-induced hemolytic anemia (DIHA) in G6PD-deficient patients, focusing on dapsone, amoxicillin, and primaquine. These drugs are essential for treating infections such as leprosy and malaria. However, they can damage red blood cell (RBC) membranes through complex mechanisms distinct from traditional immune-mediated pathways. Evidence suggests that drug metabolites, such as dapsone hydroxylamine and 5-hydroxyprimaquine, induce oxidative stress and disrupt RBC membrane integrity. The band 3 protein, a critical component of the RBC cytoskeleton, emerges as a key player in this process, undergoing tyrosine phosphorylation and aggregation, leading to membrane remodeling and instability. This review underscores the need for further research to elucidate the precise molecular interactions involved in drug-induced hemolysis in G6PD deficiency. Understanding these mechanisms may pave the way for developing targeted therapies, including adjuvant treatments and novel drug formulations, to mitigate the risk of hemolytic anemia in this vulnerable population.