Megaloblastic anemia

Historically, microscopy has been used to evaluate different forms of anemia, which has led to the development of a classification system based on erythrocyte morphology. This method has produced the categories of microcytic anemia, normocytic anemia and macrocytic anemia. The disorders that lead to macrocytic anemia comprise a heterogeneous group with a variety of known and postulated mechanisms.

Macrocytosis (mean corpuscular volume greater than 100 [mu][m.sup.3] [100 fL][1] is a fairly common finding. Between 1.7 percent and 3.6 percent of automated blood counts reveal macrocytosis. Of this group, up to 40 percent also show anemia.[1] Table 1 lists the common causes of "macrocytosis.

Besides having megaloblastic anemia and low serum [B.sub.12] levels, patients with pernicious anemia may have antibodies to intrinsic factor (in about one-half of cases) and gastroparietal cells.[11] There are two types of intrinsic factor antibody. On blocks vitamin [B.sub.12] binding to intrinsic factor, and the other binds to the intrinsic factor-[B.sub.12] complex, impairing absorption. In advanced cases, the patient may be pancytopenic. The Schilling test is used to document the low oral absorption of [B.sub.12] that is typical of pernicious anemia.[12] Table 5 lists causes of [B.sub.12] deficiency.

REFERENCES

[1.] Lee GR. Megaloblastic and nonmegaloblastic macrocytic anemias. In: Lee GR, Bithell TC, Foerster J, Athens JW, Lukens JN, eds. Wintrobe's Clinical hematology. 9th ed. Philadelphia: Lea & Febiger, 1993:745-90. [2.] Colon-Otero G, Menke D, Hook CC. A practical approach to the differential diagnosis and evaluation of the adult patient with macrocytic anemia. Med Clin North Am 1992;76:581-97. [3.] Taheri MR, Wickremasinghe RG, Jackson BF, Hoffbrand AV. The effect of folate analogues and vitamin [B.sub.12] on provision of thymine nucleotides for DNA synthesis in megaloblastic anemia. Blood 1982;59:634-40. [4.] Bond AN, Harris G, Wickramasinghe SN. DNA chain elongation rates in marrow cells from vitamin [B.sub.12]-deficient patients and methotrexate-treated mice. Br J Haematol 1982;50:299-307. [5.] Wallerstein RO Jr. Laboratory evaluation of anemia. West J Med 1987;146:443-51. [6.] Herbert V. Recommended dietary intakes (RDI) of vitamin [B.sub.12] in humans. Am J Clin Nutr 1987; 45:671-8. [7.] Healton EB, Savage DG, Brust JC, Garrett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency Medicine 1991;70:229-45. [8.] Carmel R, Sinow RM, Karnaze DS. Atypical cobalamin deficiency. Subtle biochemical evidence of deficiency is commonly demonstrable in patients without megaloblastic anemia and is often associated with protein-bound cobalamin malabsorption. J Lab Clin Med 1987;109:454-63. [9.] Lindenbaum J, Healton EB, Savage DG, Brust JC, Garrett TJ, Podell ER, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988; 318;1720-8. [10.] Pruthi RK, Tefferi A. Pernicious anemia revisited. Mayo Clin Proc 1994;69:144-50. [11.] Carmel R. Pernicious anemia. The expected findings of very low serum cobalamin levels, anemia, and macrocytosis are often lacking. Arch Intern Med 1988;148:1712-4. [12.] Nickoloff E. Schilling test: physiologic basis for and use as a diagnostic test. Crit Rev Clin Lab Sci 1988; 26:263-76. [13.] Beck WS. Neuropsychiatric consequences of cobalamin deficiency. Adv Intern Med 1991;36:33-56. [14.] Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc 1992;40:168-72. [15.] Sjoblom SM, Sipponen P, Jarvinen H. Gastroscopic follow up of pernicious anaemia patients. Gut 1993;34:28-32. [16.] Hsing AW, Hansson LE, McLaughlin JK, Nyren O, Blot WJ, Ekbom A, et al. Pernicious anemia and subsequent cancer. A population-based cohort study. Cancer 1993;71:745-50. [17.] Talley NJ, Chute CG, Larson DE, Epstein R, Lydick EG, Melton LJ 3d. Risk for colorectal adenocarcinoma in pernicious anemia. A population-based cohort study. Ann Intern Med 1989;111:738-42. [18.] Brinton LA, Gridley G, Hrubec Z, Hoover R, Fraumeni JF Jr. Cancer risk following pernicious anaemia. Br J Cancer 1989;59:810-3. [19.] Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin [B.sub.12] without intrinsic factor. Acta Med Scand 1968; 184:247-58. [20.] Waife SO, Jansen CJ Jr, Crabtree RE, Grinnan EL, Fouts PJ. Oral vitamin [B.sub.12] without intrinsic factor in the treatment of pernicious anemia. Ann Intern Med 1963;58:810-3. [21.] Savage D, Lindenbaum J. Relapses after interruption of cyanocobalamin therapy in patients with pernicious anemia. Am J Med 1983;74:765-72. [22.] Lindenbaum J. Status of laboratory, testing in the diagnosis of megaloblastic anemia. Blood 1983;61: 624-7. [23.] Waxman S, Corcino JJ, Herbert V Drugs, toxins and dietary, amino acids affecting vitamin [B.sub.12] or folic acid absorption or utilization. Am J Med 1970;48: 599-608. [24.] Fone DJ, et al. CO [B.sub.12] absorption after gastrectomy, ileal resection and in coeliac disorders. Gut 1961;2: 218-22. [25.] Toskes PP, Hansell J, Cerda J, Deren JJ. Vitamin [B.sub.12] malabsorption in chronic pancreatic insufficiency. N Engl J Med 1971;284:627-32. [26.] Rostand SG. Vitamin [B.sub.12] levels and nerve conduction velocities in patients undergoing maintenance hemodialysis. Am J Clin Nutr 1976;29:691-7. [27.] Shimoda SS, Saunders DR, Rubin CE. The Zollinger-Ellison syndrome with steatorrhea. II. The mechanism of fat and vitamin [B.sub.12] malabsorption. Gastroenterology 1968;55:705-23. [28.] Lindenbaum J. Folate and vitamin [B.sub.12] deficiencies in alcoholism. Semin Hematol 1980;17:119-29. [29.] Stimmel B, Korts D, Jackson G, Gilbert HS. Failure of mean red cell volume to serve as a biologic marker for alcoholism in narcotic dependence. A randomized control trial. Am J Med 1983;74:369-74. [30.] Horton L, Coburn RJ, England JM, Himsworth RL. The haematology of hypothyroidism. Q J Med 1976;45:101-23.

The Author

JOHN DAVENPORT, M.D., J.D. is a family physician at Kaiser Permanente Medical Center, Anaheim, Calif. He received his medical degree from the Medical University of South Carolina College of Medicine, Charleston, and his juris doctorate from Western State University of Law of Orange County, Fullerton, Calif. He attended undergraduate school at the Georgia Institute of Technology, Atlanta.

Adress correspondence to John Davenport, M.D., J.D., Kaiser Foundation Research Institute, Department of Medical Editing, 1800 Harrison St., 16th floor, Oakland, CA 94612-3429.

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