Figure 2.

Scheme of main mechanism involved in oxidative stress and hemolytic clinical manifestations in Sickle Cell Disease, G6PDH deficiency, and PK deficiency. In SCD, highly unstable HbS will be converted in MetHb, favoring band 3 clustering and dissociation from membrane complexes, inducing membrane disorganization and membrane fragility. In G6PD, dramatic reduction of NADPH levels diminishes the antioxidant capacity of RBCs increasing ROS-induced hemolysis. In PKD, diminished ATP levels affect the functioning of membrane proteins such as Na⁺/K⁺ pump or PMCA pump, which will indirectly induce water efflux and RBC dehydration, incrementing RBC fragility and hemolysis.