Overall mechanism
Unbalanced Hb synthesis; low/no B or a-globin chain
B chain has two genes (BB), usually point mutations
a chain has 4 genes (aa/aa), usually deletions
Partner globins precipitate, damage to RBCs, haemolysis
Extramedullary haematoporesis (spleen, liver, bone)
Kept in population due to malaria protection advantage
Disease severity depends on retention of HbF
