The anaemia in beta thalassemia major is multifactorial. It is in part due to the defect in globin chain synthesis leading a hypochromic microcytic anemia, in part due to a shortened red cell survival and in part due to ineffective erythropoiesis. Ineffective erythropoiesis is the result of alpha chain deposition in erythroblasts, which leads to apoptosis and ingestion of erythroblasts by macrophages. It is the hyperplastic ineffective erythropoiesis that is responsible for many of the pathological effects of untreated or undertreated thalassemia major.

The bone marrow aspirate films illustrated are from a boy with beta thalassemia major, aged 3 years 6 months, who had been regularly transfused from the age of 6 months. He had been on chelation therapy with subcutaneous deferoxamine (desferrioxamine) 6 nights a week from the age of 18 months with the most recent serum ferritin being 1800 μg/l. Hepatic iron was 4.4 mg/g. The bone marrow aspiration was performed prior to a hemopoietic stem cell transplant.

The May–Grünwald–Giemsa-stained film (left) shows hyperplastic erythropoiesis and two macrophages containing ingested erythroblasts and cellular debris. The Perls-stained film (right) shows iron-laden macrophages containing multiple ingested erythroblasts. The films provide a visual representation of the ineffective erythropoiesis of beta thalassemia major, showing the striking death of bone marrow erythroblasts. The macrophages are their graveyard.