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. 1978 Apr;128(4):294–304.

The Laboratory Diagnosis of Megaloblastic Anemias

Ralph Carmel 1
PMCID: PMC1238100  PMID: 351964

Abstract

The diagnostic approach to megaloblastic anemia involves four usually sequential steps. The first step, recognition of megaloblastosis, requires attention to altered blood cell size and morphology. These changes may sometimes be subtle or masked. The cornerstone of the second step, identification of the specific vitamin deficiency, is assay of serum vitamin B12 and folic acid levels, although they may occasionally be misleading. The third step, identification of the specific disease entity responsible for the vitamin deficiency, generally revolves around tests of absorption and gastric function. The fourth step, reevaluation after replacement therapy, is often not thought of as a diagnostic step but carries important diagnostic implications and is sometimes the only way in which coexisting abnormalities can be unmasked and identified.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARDEMAN S., CHANARIN I., FRANKLAND A. W. THE PELGER-HUUET ANOMALY AND MEGALOBLASTIC ANEMIA. Blood. 1963 Oct;22:472–476. [PubMed] [Google Scholar]
  2. Alter H. J., Zvaifler N. J., Rath C. E. Interrelationship of rheumatoid arthritis, folic acid, and aspirin. Blood. 1971 Oct;38(4):405–416. [PubMed] [Google Scholar]
  3. Arakawa T. Congenital defects in folate utilization. Am J Med. 1970 May;48(5):594–598. doi: 10.1016/0002-9343(70)90009-4. [DOI] [PubMed] [Google Scholar]
  4. Ardeman S., Chanarin I., Krafchik B., Singer W. Addisonian pernicious anaemia and intrinsic factor antibodies in thyroid disorders. Q J Med. 1966 Jul;35(139):421–431. [PubMed] [Google Scholar]
  5. Ardeman S., Chanarin I. Steroids and addisonian pernicious anemia. N Engl J Med. 1965 Dec 16;273(25):1352–1355. doi: 10.1056/NEJM196512162732502. [DOI] [PubMed] [Google Scholar]
  6. Armstrong B. K., Davis R. E., Nicol D. J., van Merwyk A. J., Larwood C. J. Hematological, vitamin B 12, and folate studies on Seventh-day Adventist vegetarians. Am J Clin Nutr. 1974 Jul;27(7):712–718. doi: 10.1093/ajcn/27.7.712. [DOI] [PubMed] [Google Scholar]
  7. BARBIER F. Un cas particulier d'hypersegmentation constitutionnelle des noyaux des neutrophiles chez l'homme. Acta Haematol. 1958 Feb;19(2):121–125. doi: 10.1159/000205421. [DOI] [PubMed] [Google Scholar]
  8. BIGGS J. C., MASON L. A., SPRAY G. H. VITAMIN-B12 ACTIVITY IN RED CELLS. Br J Haematol. 1964 Jan;10:36–42. doi: 10.1111/j.1365-2141.1964.tb00675.x. [DOI] [PubMed] [Google Scholar]
  9. BOK J., FABER J. G., DE VRIES J. A., KROESE W. F. S., NIEWEG H. O. The effect of pteroylglutamic acid administration on the serum vitamin B12 concentration in pernicious anemia in relapse. J Lab Clin Med. 1958 May;51(5):667–671. [PubMed] [Google Scholar]
  10. BOOTH C. C., MOLLIN D. L. Plasma, tissue and urinary radioactivity after oral administration of 56Co-labelled vitamin B12. Br J Haematol. 1956 Jul;2(3):223–236. doi: 10.1111/j.1365-2141.1956.tb06695.x. [DOI] [PubMed] [Google Scholar]
  11. Bashir H. V., Hinterberger H., Jones B. P. Methylmalonic acid excretion in vitamin B12 defciency. Br J Haematol. 1966 Nov;12(6):704–711. doi: 10.1111/j.1365-2141.1966.tb00156.x. [DOI] [PubMed] [Google Scholar]
  12. Bate J., Cole A. J. Rifampicin and the assay of folate and vitamin B12. Med Lab Technol. 1974 Jul;31(3):199–203. [PubMed] [Google Scholar]
  13. Beard M. E., Allen D. M. Effect of antimicrobial agents on the Lactobacillus casei folate assay. Am J Clin Pathol. 1967 Oct;48(4):401–404. doi: 10.1093/ajcp/48.4.401. [DOI] [PubMed] [Google Scholar]
  14. Beard M. E., Weintraub L. R. Hypersegmented neutrophilic granulocytes in iron deficiency anaemia. Br J Haematol. 1969 Jan-Feb;16(1):161–163. doi: 10.1111/j.1365-2141.1969.tb00388.x. [DOI] [PubMed] [Google Scholar]
  15. Bell T. K., Bridges J. M., Nelson M. G. Simultaneous free and bound radioactive vitamin B-12 urinary excretion test. J Clin Pathol. 1965 Sep;18(5):611–613. doi: 10.1136/jcp.18.5.611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bernhardt H., Burkett L. L., Fields M. L., Killian J. The diagnostic significance of the parietal cell immunofluorescent test. Ann Intern Med. 1965 Oct;63(4):635–641. doi: 10.7326/0003-4819-63-4-635. [DOI] [PubMed] [Google Scholar]
  17. Britt R. P., Rose D. P. Pernicious anemia with a normal serum vitamin B-12 level in a case of chronic granulocytic leukemia. Arch Intern Med. 1966 Jan;117(1):32–33. [PubMed] [Google Scholar]
  18. Brody E. A., Estren S., Herbert V. Coexistent pernicious anemia and malabsorption in four patients: including one whose malabsorption disappeared with vitamin B12 therapy. Ann Intern Med. 1966 Jun;64(6):1246–1251. doi: 10.7326/0003-4819-64-6-1246. [DOI] [PubMed] [Google Scholar]
  19. COX E. V., MEYNELL M. J., GADDIE R., COOKE W. T. Interrelation of vitamin B12 and iron. Lancet. 1959 Dec 5;2(7110):998–1001. doi: 10.1016/s0140-6736(59)91468-0. [DOI] [PubMed] [Google Scholar]
  20. COX E. V., WHITE A. M. Methylmalonic acid excretion: an index of vitamin-B12 deficiency. Lancet. 1962 Oct 27;2(7261):853–856. doi: 10.1016/s0140-6736(62)90631-1. [DOI] [PubMed] [Google Scholar]
  21. Carmel R., Coltman C. A., Jr, Brubaker L. H. Serum vitamin B12- binding proteins in neutropenia. Proc Soc Exp Biol Med. 1975 Apr;148(4):1217–1222. doi: 10.3181/00379727-148-38720. [DOI] [PubMed] [Google Scholar]
  22. Carmel R. Effects of antineoplastic drugs on Lactobacillus casei and radioisotopic assays for serum folate. Am J Clin Pathol. 1978 Feb;69(2):137–139. doi: 10.1093/ajcp/69.2.137. [DOI] [PubMed] [Google Scholar]
  23. Carmel R., Eisenberg L. Serum vitamin B12 and transcobalamin abnormalities in patients with cancer. Cancer. 1977 Sep;40(3):1348–1353. doi: 10.1002/1097-0142(197709)40:3<1348::aid-cncr2820400352>3.0.co;2-q. [DOI] [PubMed] [Google Scholar]
  24. Carmel R., Herbert V. Correctable intestinal defect of vitamin B12 absorption in pernicious anemia. Ann Intern Med. 1967 Dec;67(6):1201–1207. doi: 10.7326/0003-4819-67-6-1201. [DOI] [PubMed] [Google Scholar]
  25. Carmel R., Herbert V. Deficiency of vitamin B12-binding alpha globulin in two brothers. Blood. 1969 Jan;33(1):1–12. [PubMed] [Google Scholar]
  26. Chanarin I., England J. M., Mollin C., Perry J. Methylmalonic acid excretion studies. Br J Haematol. 1973 Jul;25(1):45–53. doi: 10.1111/j.1365-2141.1973.tb01714.x. [DOI] [PubMed] [Google Scholar]
  27. Chanarin I., Waters D. A. Failed Schilling tests. Scand J Haematol. 1974;12(4):245–248. doi: 10.1111/j.1600-0609.1974.tb00205.x. [DOI] [PubMed] [Google Scholar]
  28. Coiner D., Walsh J. R. Comparison of Schilling test and plasma level of cyanocobalamin Co 57. JAMA. 1971 Mar 8;215(10):1642–1645. [PubMed] [Google Scholar]
  29. Corcino J. J., Waxman S., Herbert V. Absorption and malabsorption of vitamin B 12. Am J Med. 1970 May;48(5):562–569. doi: 10.1016/0002-9343(70)90005-7. [DOI] [PubMed] [Google Scholar]
  30. Corcino J. J., Zalusky R., Greenberg M., Herbert V. Coexistence of pernicious anaemia and chronic myeloid leukaemia: an experiment of nature involving vitamin B12 metabolism. Br J Haematol. 1971 May;20(5):511–520. doi: 10.1111/j.1365-2141.1971.tb07066.x. [DOI] [PubMed] [Google Scholar]
  31. Corcino J., Waxman S., Herbert V. Mechanism of triamterene-induced megaloblastosis. Ann Intern Med. 1970 Sep;73(3):419–424. doi: 10.7326/0003-4819-73-3-419. [DOI] [PubMed] [Google Scholar]
  32. Cottrall M. F., Wells D. G., Trott N. G., Richardson N. E. Radioactive vitamin B12 absorption studies: comparison of the whole-body retention, urinary excretion, and eight-hour plasma levels of radioactive vitamin B12. Blood. 1971 Nov;38(5):604–613. [PubMed] [Google Scholar]
  33. DELLER D. J., GERMAR H., WITTS L. J. Effect of food on absorption of radioactive vitamin B12. Lancet. 1961 Mar 18;1(7177):574–577. doi: 10.1016/s0140-6736(61)92246-2. [DOI] [PubMed] [Google Scholar]
  34. Desai H. G., Zaveri M. P., Antia F. P. Letter: Increased vitamin B12 absorption after ingestion of coffee. Gastroenterology. 1973 Oct;65(4):694–695. [PubMed] [Google Scholar]
  35. Doscherholmen A., McMahon J., Ripley D. Inhibitory effect of eggs on vitamin B12 absorption: description of a simple ovalbumin 57Co-vitamin B12 absorption test. Br J Haematol. 1976 Jun;33(2):261–272. doi: 10.1111/j.1365-2141.1976.tb03537.x. [DOI] [PubMed] [Google Scholar]
  36. Eichner E. R., Hillman R. S. Effect of alcohol on serum folate level. J Clin Invest. 1973 Mar;52(3):584–591. doi: 10.1172/JCI107219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Eichner E. R., Paine C. J., Dickson V. L., Hargrove M. D., Jr Clinical and laboratory observations on serum folate-binding protein. Blood. 1975 Oct;46(4):599–609. [PubMed] [Google Scholar]
  38. Eichner E. R., Pierce H. I., Hillman R. S. Folate balance in dietary-induced megaloblastic anemia. N Engl J Med. 1971 Apr 29;284(17):933–938. doi: 10.1056/NEJM197104292841702. [DOI] [PubMed] [Google Scholar]
  39. FROST J. W., GOLDWEIN M. I. Observations on vitamin B12 absorption in primary pernicious anemia during administration of adrenocortical steroids. N Engl J Med. 1958 May 29;258(22):1096–1098. doi: 10.1056/NEJM195805292582207. [DOI] [PubMed] [Google Scholar]
  40. FUDENBERG H., ESTREN S. Non-Addisonian megaloblastic anemia; the intermediate megaloblast in the differential diagnosis of pernicious and related anemias. Am J Med. 1958 Aug;25(2):198–209. doi: 10.1016/0002-9343(58)90026-3. [DOI] [PubMed] [Google Scholar]
  41. Forshaw J., Harwood L. Diagnostic value of the serum folate assay. J Clin Pathol. 1971 Apr;24(3):244–249. doi: 10.1136/jcp.24.3.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. GLASS G. B. J., BOYD L. J., GELLIN G. A., STEPHANSON L. Uptake of radioactive vitamin B12 by the liver in humans: test for measurement of intestinal absorption of vitamin B12 and intrinsic factor activity. Arch Biochem Biophys. 1954 Jul;51(1):251–257. doi: 10.1016/0003-9861(54)90472-5. [DOI] [PubMed] [Google Scholar]
  43. GOTTLIEBLAU K. S., WASSERMAN L. R., HERBERT V. RAPID CHARCOAL ASSAY FOR INTRINSIC FACTOR (IF), GASTRIC JUICE UNSATURATED B12 BINDING CAPACITY, ANTIBODY TO IF, AND SERUM UNSATURATED B12 BINDING CAPACITY. Blood. 1965 Jun;25:875–884. [PubMed] [Google Scholar]
  44. Giorgio A. J., Trowbridge M., Boone A. W., Patten R. S. Methylmalonic aciduria without vitamin B12 deficiency in an adult sibship. N Engl J Med. 1976 Aug 5;295(6):310–313. doi: 10.1056/NEJM197608052950604. [DOI] [PubMed] [Google Scholar]
  45. Gompertz D., Jones J. H., Knowles J. P. Metabolic precursors of methylmalonic acid in vitamin-B12 deficiency. Lancet. 1967 Feb 25;1(7487):424–425. doi: 10.1016/s0140-6736(67)91181-6. [DOI] [PubMed] [Google Scholar]
  46. HEINIVAARA O., PALVA I. P. MALABSORPTION AND DEFICIENCY OF VITAMIN B 12 CAUSED BY TREATMENT WITH PARA-AMINOSALICYLIC ACID. Acta Med Scand. 1965 Mar;177:337–341. [PubMed] [Google Scholar]
  47. HEINLE R. W., WELCH A. D., SCHARF V., MEACHAM G. C., PRUSOFF W. H. Studies of excretion (and absorption) of Co60 labeled vitamin B12 in pernicious anemia. Trans Assoc Am Physicians. 1952;65:214–222. [PubMed] [Google Scholar]
  48. HERBERT V. Current concepts in therapy. Megaloblastic anemia. N Engl J Med. 1963 Feb 14;268:368–concl. doi: 10.1056/NEJM196302142680709. [DOI] [PubMed] [Google Scholar]
  49. HERBERT V. Experimental nutritional folate deficiency in man. Trans Assoc Am Physicians. 1962;75:307–320. [PubMed] [Google Scholar]
  50. HERBERT V. STUDIES OF FOLATE DEFICIENCY IN MAN. Proc R Soc Med. 1964 May;57:377–384. [PMC free article] [PubMed] [Google Scholar]
  51. HERBERT V., ZALUSKY R. Interrelations of vitamin B12 and folic acid metabolism: folic acid clearance studies. J Clin Invest. 1962 Jun;41:1263–1276. doi: 10.1172/JCI104589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Hakami N., Neiman P. E., Canellos G. P., Lazerson J. Neonatal megaloblastic anemia due to inherited transcobalamin II deficiency in two siblings. N Engl J Med. 1971 Nov 18;285(21):1163–1170. doi: 10.1056/NEJM197111182852103. [DOI] [PubMed] [Google Scholar]
  53. Hall C. A., Bardwell S. A., Allen E. S., Rappazzo M. E. Variation in plasma folate levels among groups of healthy persons. Am J Clin Nutr. 1975 Aug;28(8):854–857. doi: 10.1093/ajcn/28.8.854. [DOI] [PubMed] [Google Scholar]
  54. Hall C. A. Letters: Importance of red cell B12 and folate levels after partial gastrectomy. Am J Clin Nutr. 1974 Sep;27(9):899–900. doi: 10.1093/ajcn/27.8.899. [DOI] [PubMed] [Google Scholar]
  55. Hall C. A. Reliability of radioisotope-dilution kits for vitamin B. Lancet. 1977 Jun 11;1(8024):1255–1256. doi: 10.1016/s0140-6736(77)92457-6. [DOI] [PubMed] [Google Scholar]
  56. Halsted C. H., McIntyre P. A. Intestinal malabsorption caused by aminosalicylic acid therapy. Arch Intern Med. 1972 Dec;130(6):935–939. [PubMed] [Google Scholar]
  57. Harrison R. J. Vitamin B 12 levels in erythrocytes in hypochromic anaemia. J Clin Pathol. 1971 Nov;24(8):698–700. doi: 10.1136/jcp.24.8.698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Harrison R. J. Vitamin B12 levels in erythrocytes in anaemia due to folate deficiency. Br J Haematol. 1971 Jun;20(6):623–628. doi: 10.1111/j.1365-2141.1971.tb00800.x. [DOI] [PubMed] [Google Scholar]
  59. Henderson J. T., Simpson J. D., Warwick R. R., Shearman D. J. Does malabsorption of vitamin B 12 occur in chronic pancreatitis? Lancet. 1972 Aug 5;2(7771):241–243. doi: 10.1016/s0140-6736(72)91684-4. [DOI] [PubMed] [Google Scholar]
  60. Herbert V. Aseptic addition method for Lactobacillus casei assay of folate activity in human serum. J Clin Pathol. 1966 Jan;19(1):12–16. doi: 10.1136/jcp.19.1.12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Herbert V., Colman N., Spivack M., Ocasio E., Ghanta V., Kimmel K., Brenner L., Freundlich J., Scott J. Folic acid deficiency in the United States: folate assays in a prenatal clinic. Am J Obstet Gynecol. 1975 Sep 15;123(2):175–179. doi: 10.1016/0002-9378(75)90523-2. [DOI] [PubMed] [Google Scholar]
  62. Herbert V. Transient (reversible) malabsorption of vitamin B12. Br J Haematol. 1969 Sep;17(3):213–219. doi: 10.1111/j.1365-2141.1969.tb01364.x. [DOI] [PubMed] [Google Scholar]
  63. Hippe E., Hansen O. P., Drivsholm A. Decreased serum cobalamin in multiple myeloma without signs of vitamin B12 deficiency. A preliminary report. Scand J Gastroenterol Suppl. 1974;29:85–87. [PubMed] [Google Scholar]
  64. Hitzig W. H., Dohmann U., Pluss H. J., Vischer D. Hereditary transcobalamin II deficiency: clinical findings in a new family. J Pediatr. 1974 Nov;85(5):622–628. doi: 10.1016/s0022-3476(74)80503-2. [DOI] [PubMed] [Google Scholar]
  65. Hoffbrand A. V., Hobbs J. R., Kremenchuzky S., Mollin D. L. Incidence and pathogenesis of megaloblastic erythropoiesis in multiple myeloma. J Clin Pathol. 1967 Sep;20(5):699–705. doi: 10.1136/jcp.20.5.699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Hoffbrand A. V., Newcombe F. A., Mollin D. L. Method of assay of red cell folate activity and the value of the assay as a test for folate deficiency. J Clin Pathol. 1966 Jan;19(1):17–28. doi: 10.1136/jcp.19.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Inamdar-Deshmurkh A. B., Jathar V. S., Joseph D. A., Satoskar R. S. Erythrocyte vitamin B12 activity in healthy Indian lactovegetarians. Br J Haematol. 1976 Mar;32(3):395–401. doi: 10.1111/j.1365-2141.1976.tb00943.x. [DOI] [PubMed] [Google Scholar]
  68. JACOBSON E. D., CHODOS R. B., FALOON W. W. An experimental malabsorption syndrome induced by neomycin. Am J Med. 1960 Apr;28:524–533. doi: 10.1016/0002-9343(60)90146-7. [DOI] [PubMed] [Google Scholar]
  69. Jeffries G. H., Todd J. E., Sleisenger M. H. The effect of prednisolone on gastric mucosal histology, gastric secretion, and vitamin B 12 absorption in patients with pernicious anemia. J Clin Invest. 1966 May;45(5):803–812. doi: 10.1172/JCI105395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Jounela A. J., Pirttiaho H., Palva I. P. Drug-induced malabsorption of vitamin B12. VI. Malabsorption of vitamin B12 during treatment with phenformin. Acta Med Scand. 1974 Oct;196(4):267–269. doi: 10.1111/j.0954-6820.1974.tb01008.x. [DOI] [PubMed] [Google Scholar]
  71. KILLMANN S. A. EFFECT OF DEOXYURIDINE ON INCORPORATION OF TRITIATED THYMIDINE: DIFFERENCE BETWEEN NORMOBLASTS AND MEGALOBLASTS. Acta Med Scand. 1964 Apr;175:483–488. doi: 10.1111/j.0954-6820.1964.tb00597.x. [DOI] [PubMed] [Google Scholar]
  72. Kampa I. S., Hundertmark J. M. A comparison of results using three commercially available vitamin B-12 radioassay kits. Clin Chim Acta. 1975 Mar 10;59(2):191–194. doi: 10.1016/0009-8981(75)90028-5. [DOI] [PubMed] [Google Scholar]
  73. Kass L. A clockface chromatin pattern in the intermediate megaloblast of vitamin B 12 or folate deficiency. Blood. 1968 Nov;32(5):711–716. [PubMed] [Google Scholar]
  74. Katz M., Lee S. K., Cooper B. A. Vitamin B 12 malabsorption due to a biologically inert intrinsic factor. N Engl J Med. 1972 Aug 31;287(9):425–429. doi: 10.1056/NEJM197208312870902. [DOI] [PubMed] [Google Scholar]
  75. Killander A., Weiner L. Serum B12 determination using the radiosorbent technique and the Euglena gracilis assay. Scand J Gastroenterol Suppl. 1974;29:43–45. [PubMed] [Google Scholar]
  76. Kilpatrick G. S., Withey J. L. The serum vitamin B12 concentration in the general population. Scand J Haematol. 1965;2(3):220–229. doi: 10.1111/j.1600-0609.1965.tb01299.x. [DOI] [PubMed] [Google Scholar]
  77. LEES F. Radioactive vitamin B12 absorption in the megaloblastic anaemia caused by anticonvulsant drugs. Q J Med. 1961 Jul;30:231–248. [PubMed] [Google Scholar]
  78. Lawrence C., Klipstein F. A. Megaloblastic anemia of pregnancy in New York City. Ann Intern Med. 1967 Jan;66(1):25–34. doi: 10.7326/0003-4819-66-1-25. [DOI] [PubMed] [Google Scholar]
  79. Lillibridge C. B., Brandborg L. L., Rubin C. E. Childhood pernicious anemia. Gastrointestinal secretory, histological, and electron microscopic aspects. Gastroenterology. 1967 May;52(5):792–809. [PubMed] [Google Scholar]
  80. Lindemans J., Van Kapel J., Abels J. Evaluation of a radioassay for serum folate and the effects of ascorbate and methotrexate. Clin Chim Acta. 1975 Nov 15;65(1):15–20. doi: 10.1016/0009-8981(75)90329-0. [DOI] [PubMed] [Google Scholar]
  81. Lindenbaum J., Lieber C. S. Alcohol-induced malabsorption of vitamin B12 in man. Nature. 1969 Nov 22;224(5221):806–806. doi: 10.1038/224806a0. [DOI] [PubMed] [Google Scholar]
  82. Lindenbaum J., Pezzimenti J. F., Shea N. Small-intestinal function in vitamin B 12 deficiency. Ann Intern Med. 1974 Mar;80(3):326–331. doi: 10.7326/0003-4819-80-3-326. [DOI] [PubMed] [Google Scholar]
  83. Lindenbaum J., Whitehead N., Reyner F. Oral contraceptive hormones, folate metabolism, and the cervical epithelium. Am J Clin Nutr. 1975 Apr;28(4):346–353. doi: 10.1093/ajcn/28.4.346. [DOI] [PubMed] [Google Scholar]
  84. Longo D. L., Herbert V. Radioassay for serum and red cell folate. J Lab Clin Med. 1976 Jan;87(1):138–151. [PubMed] [Google Scholar]
  85. MCINTYRE O. R., SULLIVAN L. W., JEFFRIES G. H., SILVER R. H. PERNICIOUS ANEMIA IN CHILDHOOD. N Engl J Med. 1965 May 13;272:981–986. doi: 10.1056/NEJM196505132721901. [DOI] [PubMed] [Google Scholar]
  86. MOLLIN D. L., ROSS G. I. M. The vitamin B12 concentrations of serum and urine of normals and of patients with megaloblastic anaemias and other diseases. J Clin Pathol. 1952 May;5(2):129–139. doi: 10.1136/jcp.5.2.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Matuchansky C., Rambaud J. C., Modigliani R., Bernier J. J. Letter: Vitamin B12 malabsorption in chronic pancreatitis. Gastroenterology. 1974 Aug;67(2):406–407. [PubMed] [Google Scholar]
  88. McDonald J. W., Barr R. M., Barton W. B. Spurious Schilling test results obtained with intrinsic factor enclosed in capsules. Ann Intern Med. 1975 Dec;83(6):827–829. doi: 10.7326/0003-4819-83-6-827. [DOI] [PubMed] [Google Scholar]
  89. Metz J., Kelly A., Swett V. C., Waxman S., Herbert V. Deranged DNA synthesis by bone marrow from vitamin B-12-deficient humans. Br J Haematol. 1968 Jun;14(6):575–592. doi: 10.1111/j.1365-2141.1968.tb00364.x. [DOI] [PubMed] [Google Scholar]
  90. NYBERG W. The influence of Diphyllobothrium latum on the vitamin B12-intrinsic factor complex. I. In vivo studies with Schilling test technique. Acta Med Scand. 1960 Jul 1;167:185–187. [PubMed] [Google Scholar]
  91. Nexo E., Olesen H., Norredam K., Schwartz M. A rare case of megaloblastic anaemia caused by disturbances in the plasma cobalamin binding proteins in a patient with hepatocellular carcinoma. Scand J Haematol. 1975 Jun;14(5):320–327. doi: 10.1111/j.1600-0609.1975.tb02703.x. [DOI] [PubMed] [Google Scholar]
  92. OKUDA K., HELLIGER A. E., CHOW B. F. Vitamin B12 serum level and pregnancy. Am J Clin Nutr. 1956 Jul-Aug;4(4):440–443. doi: 10.1093/ajcn/4.4.440. [DOI] [PubMed] [Google Scholar]
  93. OSTERGAARD KRISTENSEN H. P., FRIIS T. The mechanism of the prednisone effect upon B12 absorption in pernicious anaemia. Acta Med Scand. 1960 Dec 20;168:457–459. doi: 10.1111/j.0954-6820.1960.tb06677.x. [DOI] [PubMed] [Google Scholar]
  94. Omer A., Finlayson N. D., Shearman D. J., Samson R. R., Girdwood R. H. Erythrocyte vitamin B12 activity in health, polycythemia, and in deficiency of vitamin B12 and folate. Blood. 1970 Jan;35(1):73–82. [PubMed] [Google Scholar]
  95. Omer A., Finlayson N. D., Shearman D. J., Samson R. R., Girdwood R. H. Plasma and erythrocyte folate in iron deficiency and folate deficiency. Blood. 1970 Jun;35(6):821–828. [PubMed] [Google Scholar]
  96. PEDERSEN J., LUND J., OHLSEN A. S., KRISTENSEN H. P. O. Simultaneous deficiency of iron and vitamin B12. Acta Med Scand. 1959 Mar 4;163(3):235–242. doi: 10.1111/j.0954-6820.1959.tb10403.x. [DOI] [PubMed] [Google Scholar]
  97. Palva I. P., Salokannel S. J., Palva H. L., Rytkönen U., Timonen T. Drug-induced malabsorption of vitamin B12. VII. Malabsorption of B12 treatment with potassium citrate. Acta Med Scand. 1974 Dec;196(6):525–526. doi: 10.1111/j.0954-6820.1974.tb01055.x. [DOI] [PubMed] [Google Scholar]
  98. Pierce H. I., Hillman R. S. The value of the serum vitamin B12 level in diagnosing B12 deficiency. Blood. 1974 Jun;43(6):915–921. [PubMed] [Google Scholar]
  99. REIZENSTEIN P. G., CRONKITE E. P., COHN S. H. Measurement of absorption of vitamin B12 by whole-body gamma spectrometry. Blood. 1961 Jul;18:95–101. [PubMed] [Google Scholar]
  100. Raven J. L., Robson M. B., Morgan J. O., Hoffbrand A. V. Comparison of three methods for measuring vitamin B 12 in serum: radioisotopic, euglena gracilis and Lactobacillus leichmannii. Br J Haematol. 1972 Jan;22(1):21–31. doi: 10.1111/j.1365-2141.1972.tb08783.x. [DOI] [PubMed] [Google Scholar]
  101. Reizenstein P. Errors and artefacts in serum folic-acid assays. Effects of age, food, drugs and radiation. Acta Med Scand. 1965 Aug;178(2):133–139. doi: 10.1111/j.0954-6820.1965.tb04257.x. [DOI] [PubMed] [Google Scholar]
  102. Reynolds E. H., Hallpike J. F., Phillips B. M., Matthews D. M. Reversible absorptive defects in anticonvulsant megaloblastic anaemia. J Clin Pathol. 1965 Sep;18(5):593–598. doi: 10.1136/jcp.18.5.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Rodbro P., Dige-Petersen H., Schwartz M., Dalgaard O. Z. Effect of steroids on gastric mucosal structure and function in pernicious anemia. Acta Med Scand. 1967 Apr;181(4):445–452. doi: 10.1111/j.0954-6820.1967.tb07262.x. [DOI] [PubMed] [Google Scholar]
  104. Rose M. S., Doniach D., Chanarin I., Brostoff J., Ardeman S. Intrinsic-factor antibodies in absence of pernicious anaemia. 3-7 year follow-up. Lancet. 1970 Jul 4;2(7662):9–12. doi: 10.1016/s0140-6736(70)92473-6. [DOI] [PubMed] [Google Scholar]
  105. Rosenberg L. E., Lilljeqvist A., Hsia Y. E. Methylmalonic aciduria: metabolic block localization and vitamin B 12 dependency. Science. 1968 Nov 15;162(3855):805–807. doi: 10.1126/science.162.3855.805. [DOI] [PubMed] [Google Scholar]
  106. Rothenberg S. P., da Costa M., Lawson J., Rosenberg Z. The determination of erythrocyte folate concentration using a two-phase ligand-binding radioassay. Blood. 1974 Mar;43(3):437–443. [PubMed] [Google Scholar]
  107. SCHILLING R. F. Intrinsic factor studies II. The effect of gastric juice on the urinary excretion of radioactivity after the oral administration of radioactive vitamin B12. J Lab Clin Med. 1953 Dec;42(6):860–866. [PubMed] [Google Scholar]
  108. SIURALA M. Gastric lesion in some megaloblastic anemias; results of follow-up examinations. Acta Med Scand. 1956 Jun 9;154(5):337–348. doi: 10.1111/j.0954-6820.1956.tb14329.x. [DOI] [PubMed] [Google Scholar]
  109. SULLIVAN L. W., HERBERT V., CASTLE W. B. IN VITRO ASSAY FOR HUMAN INTRINSIC FACTOR. J Clin Invest. 1963 Sep;42:1443–1458. doi: 10.1172/JCI104829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Sage R. E. Polycythemia rubra vera with pernicious anemia. Some observations on vitamin B 12 metabolism. Blood. 1969 Jul;34(1):14–24. [PubMed] [Google Scholar]
  111. Salokannel S. J., Palva I. P., Takkunen J. T. Malabsorption of vitamin B 12 during treatment with slow-release potassium chloride. Preliminary report. Acta Med Scand. 1970 May;187(5):431–432. doi: 10.1111/j.0954-6820.1970.tb02967.x. [DOI] [PubMed] [Google Scholar]
  112. Samloff I. M., Kleinman M. S., Turner M. D., Sobel M. V., Jeffries G. H. Blocking and binding antibodies to intrinsic factor and parietal call antibody in pernicious anemia. Gastroenterology. 1968 Nov;55(5):575–583. [PubMed] [Google Scholar]
  113. Schreiber C., Waxman S. Measurement of red cell folate levels by 3H-pteroylglutamic acid (3H-PteGlu) radioassay. Br J Haematol. 1974 Aug;27(4):551–558. doi: 10.1111/j.1365-2141.1974.tb06620.x. [DOI] [PubMed] [Google Scholar]
  114. Scott R. B., Kammer R. B., Burger W. F., Middleton F. G. Reduced absorption of vitamin B12 in two patients with folic acid deficiency. Ann Intern Med. 1968 Jul;69(1):111–114. doi: 10.7326/0003-4819-69-1-111. [DOI] [PubMed] [Google Scholar]
  115. Shojania A. M., Hornady G. Effect of antimicrobial agents on serum folate assay. Am J Clin Pathol. 1969 Oct;52(4):454–456. doi: 10.1093/ajcp/52.4.454. [DOI] [PubMed] [Google Scholar]
  116. Streeter A. M., O'Neill B. J. Effect of incubation time on the L. casei bioassay of folic acid in serum. Blood. 1969 Aug;34(2):216–221. [PubMed] [Google Scholar]
  117. Streiff R. R. Folic acid deficiency anemia. Semin Hematol. 1970 Jan;7(1):23–39. [PubMed] [Google Scholar]
  118. Sullivan L. W. Differential diagnosis and management of the patient with megaloblastic anemia. Am J Med. 1970 May;48(5):609–617. doi: 10.1016/0002-9343(70)90011-2. [DOI] [PubMed] [Google Scholar]
  119. Tisman G., Herbert V. B 12 dependence of cell uptake of serum folate: an explanation for high serum folate and cell folate depletion in B 12 deficiency. Blood. 1973 Mar;41(3):465–469. [PubMed] [Google Scholar]
  120. Tomkin G. H., Hadden D. R., Weaver J. A., Montgomery D. A. Vitamin-B12 status of patients on long-term metformin therapy. Br Med J. 1971 Jun 19;2(5763):685–687. doi: 10.1136/bmj.2.5763.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Ueda M., Taketa K. Effect of vitamin B12 derivatives on urinary excretion of methylmalonic acid in liver diseases. Acta Med Okayama. 1970 Jun;24(3):365–372. [PubMed] [Google Scholar]
  122. Ungar B., Stocks A. E., Martin F. I., Whittingham S., Mackay I. R. Intrinsic-factor antibody, parietal-cell antibody, and latent pernicious anaemia in diabetes mellitus. Lancet. 1968 Aug 24;2(7565):415–417. doi: 10.1016/s0140-6736(68)90462-5. [DOI] [PubMed] [Google Scholar]
  123. Vaish S. K., Sampathkumar J., Jacob R., Baker S. J. The stomach in tropical sprue. Gut. 1965 Oct;6(5):458–465. doi: 10.1136/gut.6.5.458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  124. Van der Weyden M. B., Rother M., Firkin B. G. The metabolic significance of reduced serum B 12 in folate deficiency. Blood. 1972 Jul;40(1):23–30. [PubMed] [Google Scholar]
  125. Van der Weyden M., Rother M., Firkin B. Megaloblastic maturation masked by iron deficiency: a biochemical basis. Br J Haematol. 1972 Mar;22(3):299–307. doi: 10.1111/j.1365-2141.1972.tb05676.x. [DOI] [PubMed] [Google Scholar]
  126. WHITESIDE M. G., MOLLIN D. L., COGHILL N. F., WILLIAMS A. W., ANDERSON B. THE ABSORPTION OF RADIOACTIVE VITAMIN B12 AND THE SECRETION OF HYDROCHLORIC ACID IN PATIENTS WITH ATROPHIC GASTRITIS. Gut. 1964 Oct;5:385–399. doi: 10.1136/gut.5.5.385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  127. Waters W. E., Withey J. L., Kilpatrick G. S., Wood P. H. Serum vitamin B 12 concentrations in the general population: a ten-year follow-up. Br J Haematol. 1971 May;20(5):521–526. doi: 10.1111/j.1365-2141.1971.tb07067.x. [DOI] [PubMed] [Google Scholar]
  128. Webb D. I., Chodos R. B., Mahar C. Q., Faloon W. W. Mechanism of vitamin B12 malabsorption in patients receiving colchicine. N Engl J Med. 1968 Oct 17;279(16):845–850. doi: 10.1056/NEJM196810172791602. [DOI] [PubMed] [Google Scholar]
  129. Wertalik L. F., Metz E. N., LoBuglio A. F., Balcerzak S. P. Decreased serum B 12 levels with oral contraceptive use. JAMA. 1972 Sep 18;221(12):1371–1374. [PubMed] [Google Scholar]
  130. Wheby M. S., Bayless T. M. Intrinsic factor in tropical sprue. Blood. 1968 Jun;31(6):817–820. [PubMed] [Google Scholar]

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