Difference between normal and β-thalassemia ineffective erythropoiesis. Erythropoiesis is the pathway producing mature RBCs from hematopoietic stem cells, including several proliferation and differentiation steps. Erythroid differentiation is accompanied by temporally regulated changes in cell surface protein expression, reduction in cell size, progressive hemoglobinization, and nuclear condensation and extrusion. β-thalassemia dyserythropoiesis in human is characterized by expansion of very early erythroid precursors (proerythroblasts and earlier stages) and then ineffective erythropoiesis. Ineffective erythropoiesis defines the suboptimal production of mature erythrocytes from a proliferating pool of immature erythroblasts characterized by (1) accelerated erythroid differentiation, (2) maturation blockade at the polychromatophilic stage, and (3) death of erythroid precursors.