While megaloblastosis is directly defined by its morphology, the mechanism of the anemia is complex. In general, anemia due to excessive destruction of red cells is characteristically associated with a cellular marrow and a high output of reticu-locytes, whereas anemia due to decreased production of red cells is characteristically associated with hypocellular marrow and a low output of reticulocytes. In megaloblastic anemia, the marrow is hypercellular, often to an extreme degree, but the output of reticulocytes is low. This contrast is the pathophysiological hallmark of megaloblastic anemia, and it signifies that a large proportion of megaloblasts fail to mature into viable red cells; in other words, there is a vast component of ineffective erythropoiesis.
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