Haema 2013; 4(1):13-22
by Menelaos Papoutselis, Evdoxia Douvali, Ioannis Kotsianidis
Hematology Department, Democritus University of Thrace School of Medicine, Alexandroupolis, Greece
Macrocytosis of red blood cells is an often encountered laboratory finding which may be accompanied or not from anemia. The prevalence of macrocytosis in the general population ranges from 1.7% to 3.6%, whereas it is significantly higher in older patients. Macrocytic anemias are largely classified as those resulting from disorders of DNA synthesis in the bone marrow erythrocyte progenitors (megaloblastic anemias) or those that are not associated with megaloblastoid abnormalities, which have heterogeneous etiology and are caused primarily by alcoholism, liver disease and hypothyroidism (non- megaloblastic anemias). The evaluation of the patient with macrocytosis requires a systemic approach. A comprehensive history and physical examination followed by appropriate laboratory studies that include a complete blood count, a peripheral blood smear and reticulocyte count are all mandatory. In selected cases, a bone marrow examination and/or specialized hematologic work up may be necessary. Megaloblastic anemias share specific bone marrow and peripheral blood features, such as asynchronous nuclear/cytoplasmic maturation, giant metamyelocytes, hypersegmented neutrophils. The causes of meg- aloblastic anemia include deficiency of vitamin B12 and/or folate, inherited and acquired abnormalities affecting the metabolism of these vitamins, the myelodysplastic syndromes and other defects in DNA synthesis. The clinical features of megaloblastic anemia due to vitamin B12/folate deficiency apart from the general manifestations of anemia include glossitis, angular cheilitis, jaundice and neuropsychiatric disturbances. Typical hematological findings include pancytopenia, accumulation of unconjugated bilirubin in plasma and raised serum lactate dehydrogenase. Treatment is based mainly on cobalamin and folate administration, whereas in the rest cases of megaloblastic anemia the therapeutic strategy is directed towards the primary cause. Non-megaloblastic macrocytic anemias may be accompanied by in- creased reticulocyte counts, e.g. hemolysis, hemorrhage or by normal or decreased reticulocyte counts as occurs in alcoholism, liver disease, hypothyroidism and various bone marrow disorders). The most common form of nonmegaloblastic macrocytic anemia results from alcoholism. Alcohol interferes with lipid metabolism, causing defects in lipid synthesis and affecting the formation of the erythrocyte membrane, while deficiency of either vitamin B12 or folate often coexists.