Chapter 100. Megaloblastic Anemias (Part 15)

Folinic Acid (5-Formyl-Thf) This is a stable form of fully reduced folate. It is given orally or parenterally to overcome the toxic effects of methotrexate or other DHF reductase inhibitors.Prophylactic Folic AcidIn many countries, food is fortified with folic acid (in grain or flour) to prevent neural tube defects. It is also used in chronic dialysis patients and in parenteral feeds. Prophylactic folic acid has been used to reduce homocysteinelevels to prevent cardiovascular disease, but further data are needed to assess the benefit for this and for cognitive function in the elderly.PregnancyFolic acid, 400 µg daily, should be given...
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Chapter 100. Megaloblastic Anemias (Part 15) Chapter 100. Megaloblastic Anemias (Part 15) Folinic Acid (5-Formyl-Thf) This is a stable form of fully reduced folate. It is given orally orparenterally to overcome the toxic effects of methotrexate or other DHF reductaseinhibitors. Prophylactic Folic Acid In many countries, food is fortified with folic acid (in grain or flour) toprevent neural tube defects. It is also used in chronic dialysis patients and inparenteral feeds. Prophylactic folic acid has been used to reduce homocysteinelevels to prevent cardiovascular disease, but further data are needed to assess thebenefit for this and for cognitive function in the elderly. Pregnancy Folic acid, 400 µg daily, should be given as a supplement before andthroughout pregnancy. In women who have had a previous fetus with a neural tubedefect, 5 mg daily is recommended when pregnancy is contemplated andthroughout the subsequent pregnancy. Infancy and Childhood The incidence of folate deficiency is so high in the smallest prematurebabies during the first 6 weeks of life that folic acid (e.g., 1 mg daily) should begiven routinely to those weighing Megaloblastic Anemia Not Due to Cobalamin or Folate Deficiency orAltered Metabolism This may occur with many antimetabolic drugs (e.g.,. hydroxyurea,cytosine arabinoside, 6-mercaptopurine) that inhibit DNA replication. Antiviralnucleoside analogues used in treatment of HIV infection may also causemacrocytosis and megaloblastic marrow changes. In the rare disease oroticaciduria, two consecutive enzymes in purine synthesis are defective. The conditionresponds to therapy with uridine, which by-passes the block. In thiamine-responsive megaloblastic anemia, there is a genetic defect in the high-affinitythiamine transport (SLC19A2) gene. This causes defective RNA ribose synthesisthrough impaired activity of transketolase, a thiamine-dependent enzyme in thepentose cycle. This leads to reduced nucleic acid production. It may be associatedwith diabetes mellitus and deafness and the presence of many ringed sideroblastsin the marrow. The explanation is unclear for megaloblastic changes in themarrow in some patients with acute myeloid leukemia and myelodysplasia. Further Readings Bazzano LA et al: Effect of folic acid supplementation on risk ofcardiovascular diseases. JAMA 296:2720, 2006 [PMID: 17164458] Bønaa KH et al: Homocysteine lowering and cardiovascular events afteracute myocardial infarction. N Engl J Med 354:1578, 2006 [PMID: 18008384] Chan JCW et al: Pernicious anemia in Chinese: A study of 181 patients in aHong Kong Hospital. Medicine 85:129, 2006 Durga J et al: Effect of 3-year folic acid supplementation on cognitivefunction in older adults in the FACIT trial: A randomized double-blind, controlledtrial. Lancet 369:208, 2007 [PMID: 17240287] Hershko C et al: Variable hematologic presentation of autoimmunegastritis: Age-related progression from iron deficiency to cobalamin depletion.Blood 107:1673, 2006 [PMID: 16239424] Lonn E et al: Homocysteine lowering with folic acid and B vitamins invascular disease. N Engl J Med 354:1567, 2006 [PMID: 16531613] McMahon JA et al: A controlled trial of homocysteine lowering andcognitive performance. N Engl J Med 354:2764, 2006 [PMID: 16807413] Mills JL et al: Low vitamin B12 concentrations in patients without anemia:The effect of folic acid fortification of grain. Am J Clin Nutr 77:1474, 2003[PMID: 12791626] Rothenberg SP et al: Autoantibodies against folate receptors in women witha pregnancy complicated by a neural tube defect. N Engl J Med 350:134, 2004[PMID: 14711912] Sazawal S et al: Effects of routine prophylactic supplementation with ironand folic acid on admission to hospital and mortality in preschool child mortalityin Southern Nepal: Community-based, cluster-randomized, placebo-controlledtrial. Lancet 367:144, 2006 Bibliography Chanarin I, Metz J: Diagnosis of cobalamin deficiency: The old and thenew. Br J Haematol 97:695, 1997 [PMID: 9217166] Halfdanason TR et al: Hematologic manifestations of celiac disease. Blood109:412, 2007 He Q et al: Amnionles function is required for cubilin brush-borderexpression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo. Blood106:1447, 2005 [PMID: 15845892] Hershko C et al: Role of autoimmune gastritis, Helicobacter pylori andceliac disease in refractory or unexplained iron deficiency anemia. Haematologica90:585, 2005 [PMID: 15921373] Solomon LR: Cobalamin-responsive disorders in the ambulatory casesetting: Unreliability of cobalamin, methylmalonic acid a ...