Mechanisms by which normal erythropoiesis would fail. Because EBIs contain both DBA and normal erythroid cells, the high heme export from DBA CFU-E/proerythroblasts to the central macrophage might saturate its uptake mechanism and/or its processing abilities (eg, HMOX1). This could then inhibit further heme export from both DBA and normal CFU-E/proerythroblasts that share this EBI, and both die of resulting heme toxicities. An alternative possibility is that the excessive heme disrupts central macrophage transcription, translation, or hemoprotein formation and thus disrupts its “nurse cell” function, impairing the differentiation of all (ie, DBA and normal) adherent red cell precursors.