B12 or Folic acid deficiency
The morphologic hallmark of megaloblastic anemias is an enlargement of erythroid precursors (megaloblasts), which gives rise to abnormally large red cells (macrocytes
granulocyte precursors are enlarged (giant metamyelocytes) and yield highly characteristic hypersegmented neutrophils
impairment of DNA synthesis, which results in a delay in nuclear maturation and cell division. Because the synthesis of RNA and cytoplasmic elements proceeds at a normal rate and thus outpaces that of the nucleus, the hematopoietic precursors show nuclear-cytoplasmic asynchrony
undergo apoptosis in the marrow (ineffective hematopoiesis
pancytopenia (anemia, thrombocytopenia, and granulocytopenia
Morphology in megaloblastic anemia:
The bone marrow is markedly hypercellular, as a result of increased numbers of megaloblasts. These cells are larger than normoblasts and have a delicate, finely reticulated nuclear chromatin (suggestive of nuclear immaturity) and an abundant, strikingly basophilic cytoplasm
As the megaloblasts differentiate and begin to acquire hemoglobin, the nucleus retains its finely distributed chromatin and fails to undergo the chromatin clumping typical of an orthochromatic normoblast
Similarly, the granulocytic precursors also demonstrate nuclear-cytoplasmic asynchrony, yielding giant metamyelocytes. Megakaryocytes, too, may be abnormally large and have bizarre multilobed nuclei.
Normally, neutrophils have three or four nuclear lobes, but in megaloblastic anemias neutrophils often have five or more.
The red cells typically include large, egg-shaped macro-ovalocytes; the MCV is often greater than 110 fL
Causes of Megaloblastic Anemia Vitamin B12 Deficiency:
Inadequate diet, vegetarianism
Intrinsic factor deficiency
Diffuse intestinal disease, e.g., lymphoma, systemic sclerosis
Ileal resection, ileitis
Competitive parasitic uptake
Fish tapeworm infestation
Bacterial overgrowth in blind loops and diverticula of bowel
Pregnancy, hyperthyroidism, disseminated cancer.