OBSERVATIONS in man and experimental animals suggest that, in severe hemolytic disease, folic acid stores may be compromised and daily folic acid requirements increased.1-7 In patients with hemolytic anemia, megaloblastic changes in the bone marrow are a recognized complication. Lindenbaum and Klipstein 4 wrote an excellent review of this subject and described a patient of their own, a woman with sickle cell anemia and folic acid deficiency. These authors objected to the majority of previous case reports describing patients with hemolytic disease and megaloblastic bone marrows because direct evidence for vitamin B12 or folic acid deficiency was lacking and because large "pharmacologic" doses of these vitamins were used for treatment.
At the University of Texas Medical Branch, a Negro boy with sickle cell anemia was observed to have a megaloblastic bone marrow during three separate hospitalizations, and each time, appropriate microbiologic assays documented folic acid deficiency. This
Alperin JB. Folic Acid Deficiency Complicating Sickle Cell Anemia: A Study on the Response to Titrated Doses of Folic Acid. Arch Intern Med. 1967;120(3):298–306. doi:10.1001/archinte.1967.00300030040008
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