Paul Schick, MD, Emeritus Professor, Department of Internal Medicine, Thomas Jefferson University MedicalCollege; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital, Wynnewood, PA
Updated: Aug 26, 2009
Megaloblastic anemias are a heterogeneous group of disorders that share common morphologic characteristics. Erythrocytes are larger and have higher nuclear-to-cytoplasmic ratios comparedto normoblastic cells. Neutrophils can be hypersegmented, and megakaryocytes are abnormal. On the molecular level in megaloblastic cells, the maturation of nuclei is delayed, while cytoplasmicdevelopment is normal.
Megaloblastosis is a generalized disorder because nonhematopoietic cells, such as gastrointestinal and uterine cervical mucosal cells, can also have megaloblastic features. Theetiology of megaloblastic anemias is diverse, but a common basis is impaired DNA synthesis. The most common causes of megaloblastosis are cobalamin (vitamin B-12) and folate deficiencies. The usual causesof cobalamin deficiency are pernicious anemia (PA, see Pernicious Anemia), failure of absorption of cobalamin in the terminal ileum, and the effects of medications. Folate deficiency is usually due tofolate-poor diets but may also occur in patients with tropical sprue, in patients who are pregnant, and in patients on antifolate or other medications. Current routine folate replacement duringpregnancy and folate-containing multivitamin supplementation for elderly persons has led to a decline in the frequency of folate deficiency.
Some patients can be asymptomatic. The development ofmegaloblastic anemia is usually insidious; therefore, patients are often relatively asymptomatic because they have had time to adjust to the marked fall in hemoglobin (Hgb) levels. Patients with cobalamin...