Anemias associated with frank megaloblastic changes in the bone marrow are usually caused by a deficiency of either cyanocobalamin (vitamin B12) or folic acid. The clinical differentiation of these deficiencies is almost entirely circumstantial and often difficult. The presence of cyanocobalamin deficiency is almost certain when a megaloblastic anemia is associated with combined system disease of the spinal cord and is probable when the secretion of gastric intrinsic factor is defective. The latter association may be suspected or established, in order of increasing certainty, by the demonstration of (1) gastric achlorhydria, (2) gastric achylia, (3) failure to absorb oral radioactive cyanocobalamin unless this is accompanied by an intrinsic factor preparation.1 Occasionally the diagnosis of vitamin B12 deficiency is facilitated by obtaining a history of total gastrectomy or, more rarely, of long-standing vegetarianism.2 Circumstantial clinical evidence of folic-acid deficiency is less specific than that of cyanocobalamin deficiency and diagnosis is usually
MARSHALL RA, JANDL JH. Responses to "Physiologic" Doses of Folic Acid in the Megaloblastic Anemias. AMA Arch Intern Med. 1960;105(3):352–360. doi:10.1001/archinte.1960.00270150006002
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