$\beta$-thalassemia major arises from grossly deficient $\beta$-globin chain production. Excess $\alpha$-globin chains have no partner, precipitate, and form toxic inclusions inside developing erythroblasts.
Because these precursors are destroyed within the marrow before maturing, the marrow churns out cells but very few usable red cells survive - the hallmark known as ineffective erythropoiesis. This is the primary lesion and the correct choice.
The cascade that follows: the huge mass of dying erythroid precursors secretes erythroferrone, which switches off hepcidin. Low hepcidin keeps ferroportin open, so dietary iron pours in; combined with lifelong transfusions this produces systemic iron overload. Thus hepcidin is suppressed (not raised), making the "hepcidin increased" option false; the "suppressed hepcidin / iron overload" statement is true but is a downstream effect, not the defining mechanism. The destruction of red cells is mainly intramedullary and splenic (extravascular), not intravascular.
\[\boxed{\text{Ineffective (defective) erythropoiesis is the central mechanism}}\]