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J KMA Special Issue Deficiency Anemia Deog Yeon Jo, MD Department of Internal Medicine, Chungnam National University College of Medicine E mail : deogyeon@cnu.ac.kr J Korean Med Assoc 2006; 49(10): 874-84 Abstract Iron deficiency anemia (IDA) and megaloblastic anemia due to vitamin B12 deficiency are well characterized prototypes of anemia. There is no doubt that IDA is the most common hematologic disorder in Korea and worldwide as well. The diagnosis and treatment of IDA is not a difficult practice usually, however, a caution is required in detecting early stage iron deficiency and in distinguishing IDA from anemia of chronic disorders such as chronic inflammatory disease, malignancies, chronic liver disease, and chronic renal disease. Administration of a standard iron preparation at a proper dosage over an adequate period is a prerequisite for the successful treatment of IDA, which is sometimes overlooked by both physicians and patients. Early detection and treatment as well as prevention of iron deficiency per se are also required. Pernicious anemia is the most common cause of vitamin B12 deficiency in Western populations. By contrast, the disorder is rare in Korea, although the number of cases seems to be increasing these days. The majority of patients with megaloblastic anemia reveal a history of gastrectomy. Thus, it should be reminded that vitamin B12 supplementation is important to prevent the development of overt deficiency or anemia in these susceptible individuals, since a delay in the treatment of vitamin B12 deficiency may result in an irreversible neurologic deficit. Keywords : Iron deficiency anemia; Serum transferrin receptor; Vitamin B12; Megaloblastic anemia; Pernicious anemia 874

Deficiency Anemia 875

Jo DY Etiology of iron deficiency anemia Increased iron requirement Immaturity, infants, adolescents Pregnancy and parturition Erythropoietin therapy Increased iron loss Neonates: feto maternal hemorrhage, twin to twin hemorrhage, bleeding during delivery Chronic gastrointestinal blood loss Menstruation (especially hypermenorrhea) Frequent blood donation Long term hemodialysis Dietary iron deficiency: unsupplemented milk diets in infants, vegetarian Malabsorption of iron: chronic diarrhea, gastrectomy 876

Deficiency Anemia 877

Jo DY 878

Deficiency Anemia 879

Jo DY 880

Deficiency Anemia 881

Jo DY 1. Lichtman MA, Beutler E, Kipps TJ, Seligsohn U, Kaushansky K, Prchal J, eds. Williams Hematology. 7th ed. New York: Mc- Graw Hill Medical, 2006: 511-53 2.,,,.. 2002; 45: 362-9 3. Cook JD. Newer aspects of the diagnosis and treatment of iron deficiency. Hematology 2003; 53-7 4. Thomas C, Thomas L. Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem 2002; 48: 1066-76 5. Labbe RF, Vreman HJ, Stevenson DK. Zinc protoporphyrin. A metablolite with a mission. Clin Chem 1999; 45: 2060-72 6. Huebers HA, Beguin Y, Pootrakul P, Einspahr D, Finch CA. Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood 1990; 75: 102-7 7. Beguin Y. Soluble transferrin receptor for the evaluation of erythropoiesis and iron status. Clin Chim Acta 2003; 329: 9-22 8. Skikne BS, Flowers CH, Cook JD. Serum transferrin receptor: a quantitative measure of tissue iron deficiency. Blood 1990; 75: 1870-6 882

Deficiency Anemia 9. Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood 2003; 101: 3359-63 10. Guyatt GH, Patterson C, Ali M, Singer J, Levine M, Turpie I, et al. Diagnosis of iron deficiency anemia in the elderly. Am J Med 1990; 88: 205-9 11. Guyatt GH, Oxman AD, Ali M, Willan A, Mcilory W, Patterson C. Laboratory diagnosis of iron deficiency anemia; an overview. J Gen Intern Med 1992; 7: 145-53 12. Intragumtornchai T, Ronjukkarin P, Swaskikul D, Israsena S. The role of serum ferritin in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis. J Intern Med 1998; 243: 233-41 13. Ferguson BJ, Skikne BS, Simpson KM, Baynes RD, Cook JD. Serum transferrin receptor distinguishes the anemia of chronic disease from iron deficiency anemia. J Lab Clin Med 1992; 119: 385-590 14. Fishbane S. Intravenous iron therapy: reweighing risk and reward. Semin Dialysis 1999; 12: 5-8 15. Drueke TB, Barany P, Cazzola M, Eschbach JW, Grutzmacher P, Kaltwasser JP, et al. Management of iron deficiency in renal anemia: guidelines for the optimal therapeutic approach in erythropoietin treated patients. Clin Nephrol 1997; 48: 1-8 16. Besarab A, Frinak S, Yee J. An indistinct balance: the safety and efficacy of parenteral iron therapy. Am J Soc Nephrol 1999; 10: 2029-43 17. Toh BH, van Driel IR, Gleeson PA. Pernicious anemia. N Engl J Med 1997; 337: 1441-8 18. Chun JM, Park NS, Park JH, Yun GW, Yang YJ, Park SE, et al. Pernicous anemia. A retrospective analysis of 22 cases. Kor J Hematol 2005; 40: 219-25 19. Song HH, Kwon JH, Kim JH, Jeong JY, Kim HJ, Lee KS, et al. Causes and clinical features of vitamin B12 deficiency megaloblastic anemia. Kor J Hematol 2004; 39: 243-8 20. Andres E, Loukili NH, Noel E, Kaltenbach G, Abelgheni MB, Perrin AE, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ 2004; 171: 251-9 21. Andres E, Perrin AE, Demangeat C, Kertz JE, Vinzio S, Grunenberger F, et al. The syndrome of food cobalamin malabsorption revisited in a department of internal medicine. A monocentric cohort study of 80 patients. Eur J Intern Med 2003; 14 :221-6 22. Toh BH, Alderuccio F. Pernicious anemia. Autoimmunity 2004; 37: 357-61 23. Perez Perez GI. Role of Helicobacter pylori infection in the development of pernicious anemia. Clin Infect Dis 1997; 25: 1020-2 24. 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 25. Sjoblom SM, Sipponen P, Jarvinen H. Gastroscopic follow up of pernicious anaemia patients. Gut 1993; 34: 28-32 26. Carmel R. Reassessment of the relative prevalence of anti bodies to gastric parietal cell and to intrinsic factor in patients with pernicious anaemia: influence of patient age and race. Clin Exp Immunol 1992; 89: 74-7 27. Doscherholmen A, Hagen PS, Liu M, Olin L. A dual mechanism of vitamin B12 plasma absorption. J Clin Invest 1957; 36: 1551-7 883

Jo DY 28. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral 29. Park MR, Shim H. Oral mecobalamin treatment in cobalamin deficiency. Kor J Hematol 2004; 39: 228-32 cobalamin. Blood 1998; 92: 1191-8 Peer Reviewer Commentary 884