Iron deficiency anaemia: A review of diagnosis, investigation and management

European Journal of Gastroenterology and Hepatology

Volumn 24, Issue 2, 2012, Pages 109-116

  Liu, Ken ^a   Kaffes, Arthur J ^b  

^a University of Sydney   (Australia)

^b ROYAL PRINCE ALFRED HOSPITAL   (Australia)

Author keywords

anaemia; colonoscopy; endoscopy; gastrointestinal bleeding; gastroscopy; iron deficiency; iron replacement; malignancy; obscure gastrointestinal bleeding; parenteral iron

Indexed keywords

ANTACID AGENT; ASCORBIC ACID; FERRIC CARBOXYMALTOSE; FERRIC GLUCONATE; FERRIC HYDROXIDE SUCROSE; FERRIC POLYMALTOSE; FERRITIN; FERUMOXYTOL; HISTAMINE H2 RECEPTOR ANTAGONIST; IRON; IRON DEXTRAN; IRON ISOMALTOSE; IRON POLYMALTOSE; PHOSPHATE; PHYTATE; PROTON PUMP INHIBITOR; TANNIN; UNCLASSIFIED DRUG;

ANAPHYLAXIS; ARTHRALGIA; ATROPHIC GASTRITIS; CAPSULE ENDOSCOPY; CELIAC DISEASE; DIARRHEA; DIFFERENTIAL DIAGNOSIS; DIGESTIVE SYSTEM INJURY; DOUBLE BALLOON ENTEROSCOPY; DRUG COST; DRUG HYPERSENSITIVITY; DRUG TREATMENT FAILURE; EPIGASTRIC DISCOMFORT; GASTROINTESTINAL HEMORRHAGE; GASTROINTESTINAL TUMOR; HELICOBACTER INFECTION; HUMAN; HYPOTENSION; IRON ABSORPTION; IRON DEFICIENCY ANEMIA; IRON THERAPY; NAUSEA; PARTIAL GASTRECTOMY; PATIENT COMPLIANCE; POSTOPERATIVE COMPLICATION; PREMENOPAUSE; PRIORITY JOURNAL; REVIEW; STOMACH BYPASS; VOMITING;

ANEMIA, IRON-DEFICIENCY; ENDOSCOPY, GASTROINTESTINAL; GASTROINTESTINAL HEMORRHAGE; HUMANS; IRON;

EID: 84855897978     PISSN: 0954691X     EISSN: 14735687     Source Type: Journal    
DOI: 10.1097/MEG.0b013e32834f3140     Document Type: Review

References (87)

1. WHO. Worldwide prevalence of anaemia 1993-2005: WHO global database on anaemia. Geneva: World Health Organization; 2008.
2. WHO. Iron deficiency anaemia: Assessment, prevention, and control A guide for programme managers. Geneva: World Health Organisation; 2001.
3. Looker AC, Dallman PR, Carroll MD, Gunter MW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA 1997; 277:973-976. (Pubitemid 27142364)
4. McIntyre AS, Long RG. Prospective survey of investigations in outpatients referred with iron deficiency anaemia. Gut 1993; 34:1103-1107.
5. Rockey DC. Occult gastrointestinal bleeding.N Engl JMed 1999; 341:38-46. (Pubitemid 29293719)
6. Rockey DC, Cello JP. Evaluation of gastrointestinal tract in patients with irondeficiency anemia. N Engl J Med 1993; 329:1691-1695. (Pubitemid 23346919)
7. Kepczyk T, Kadakia SC. Prospective evaluation of gastrointestinal tract in patients with iron-deficiency anemia. Dig Dis Sci 1995; 40:1283-1289.
8. Ioannou GN, Spector J, Rockey DC. Predictors of endoscopic and laboratory evaluation of iron deficiency anemia in hospitalized patients. Southern Med J 2007; 100:976-984. (Pubitemid 47537881)
9. Park JS, Park DI, Park SK, Choi JS, Kim YH, Chang DK, et al. Endoscopic evaluation of significant gastrointestinal lesions in patients with iron deficiency with and without anaemia: A Korean Association for the Study of Intestinal Disease Study. Internal Med J 2009; 39:441-446.
10. Cook IJ, Pavli P, Riley JW, Goulston KJ, Dent OF. Gastrointestinal investigation of iron deficiency anaemia. BMJ 1986; 292:1380-1382. (Pubitemid 16081823)
11. Fleming RE, Bacon BR. Orchestration of iron homeostasis. N Engl J Med 2005; 352:1741-1744. (Pubitemid 40570920)
12. Andrews NC. Disorders of iron metabolism. N Engl J Med 1999; 341:1986-1995. (Pubitemid 30010408)
13. Ahlquist DA. Approach to the patient with occult gastrointestinal bleeding. In: Yamada T, editor. Textbook of gastroenterology. 2nd ed. Philadelphia: J. B. Lippincott; 1995. pp. 699-717.
14. Hardwick RH, Armstrong CP. Synchronous upper and lower gastrointestinal endoscopy is an effective method of investigating iron-deficiency anaemia. Br J Surg 1997; 84:1725-1728. (Pubitemid 27519606)
15. Niv E, Elis A, Zissin R, Naftali T, Novis B, Lishner M. Iron deficiency anemia in patients without gastrointestinal symptoms: A prospective study. Family Practice 2005; 22:58-61. (Pubitemid 40309606)
16. Ho C, Chau W, Hsu H, Gau J, You J, Chen C. Predictive risk factors and prevalence of malignancy in patients with iron deficiency anemia in Taiwan. Am J Hematol 2005; 78:108-112. (Pubitemid 40194101)
17. James MW, Chen C, Goddard WP, Scott BB, Goddard AF. Risk factors for gastrointestinal malignancy in patients with iron-deficiency anaemia. Eur J Gastroenterol Hepatol 2005; 17:1197-1203. (Pubitemid 41527437)
18. Ioannou GN, Rockey DC, Bryson CL, Weiss NS. Iron deficiency and gastrointestinal malignancy: A population-based cohort study. Am J Med 2002; 113:276-280. (Pubitemid 35287292)
19. Majid S, Salih M,Wasaya R, JafriW. Predictors of gastrointestinal lesions on endoscopy in iron deficiency anemia without gastrointestinal symptoms. BMC Gastroenterol 2008; 8:52.
20. Capurso G, Baccini F, Osborn J, Panzuto F, Guilio ED, Delle Fave G, et al. Can patient characteristics predict the outcome of endoscopic evaluation of iron deficiency anemia: A multiple logistic regression analysis. Gastrointest Endosc 2004; 59:766-771. (Pubitemid 38879302)
21. Annibale B, Capruso G, Chistolini A, D'Ambra G, DiGuilio E, Monarca B, et al. Gastrointestinal causes of refractory iron deficiency anemia in patients without gastrointestinal symptoms. Am J Med 2001; 111:439-445. (Pubitemid 33016414)
22. Corazza GR, Valentini RA, Andreani ML, D'Anchino M, Leva MT, Ginaldi L, et al. Subclinical coeliac disease is a frequent cause of iron deficiency anaemia. Scan J Gastroenterol 1995; 30:153-156.
23. Fine KD. The prevalence of occult gastrointestinal bleeding in celiac sprue. N Engl J Med 1996; 334:1163-1167. (Pubitemid 26137975)
24. Rockey DC. Occult gastrointestinal bleeding. Gastroenterol Clin N Am 2005; 34:699-718. (Pubitemid 41643127)
25. Ciacci C, Sabbatini F, Cavallaro R, Castiglione F, Di Bella S, Iovino P, et al. Helicobacter pylori impairs iron absorption in infected individuals. Dig Liver Dis 2004; 36:455-460. (Pubitemid 41115448)
26. Nahon S, Lahmek P, Massard J, Lesgourgues B, Mariaud de Serre M, Traissac L, et al. Helicobacter pylori-associated chronic gastritis and unexplained iron deficiency anemia: A reliable association? Helicobacter 2003; 8:573-577. (Pubitemid 37553429)
27. Muhsen K, Cohen D. Helicobacter pylori infection and iron stores: A systematic review and meta-analysis. Helicobacter 2008; 13:323-340.
28. Bini EJ. Helicobacter pylori and iron deficiency anemia: guilty as charged? Am J Med 2001; 111:495-497. (Pubitemid 33016425)
29. Mizon C, Ruz M, Csendes A, Carrasco F, Rebolledo A, Codoceo J, et al. Persistent anemia after Roux-en-Ygastric bypass. Nutrition 2007; 23:277-280.
30. Geokas MC, McKenna RD. Iron-deficiency anemia after partial gastrectomy. Can Med Assoc J 1967; 96:411-417.
31. Tovey FI, Godfrey JE, Lewin MR. A gastrectomy population: 25-30 years on. Postgrad Med J 1990; 66:450-456. (Pubitemid 20187961)
32. Finberg KE, Heeney MM, Campagna DR, Aydinok Y, Pearson HA, Hartman KR, et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 2008; 40:569-571. (Pubitemid 351601217)
33. Reynolds RD, Binder HJ, Miller MB, Chang WW, Horan S. Pagophagia and iron deficiency anemia. Ann Intern Med 1968; 69:435-440.
34. Goddard AF, James MW, McIntyre AS, Scott BB. Guidelines for the management of iron deficiency anaemia. British Society of Gastroenterology. Gut 2000; 46 (Suppl 3-4):IV1-IV5. (Pubitemid 30441235)
35. Beutler E, Hoffbrand AV, Cook JD. Iron deficiency and overload. Haematology (Am Soc Hematol Educ Program) 2003;40-61.
36. Mazza J, Barr RM, McDonald JWD, Valberg LS. Usefulness of the serum ferritin concentration in the detection of iron deficiency in a general hospital. Can Med Assoc J 1978; 119:884-886. (Pubitemid 9056946)
37. Guyatt GH, Oxman AD, Ali M,Willan A, McIlroy W, Patterson C. Laboratory diagnosis of iron-deficiency anemia: An overview. J Gen Intern Med 1992; 7:145-153.
38. Finch CA, Bellotti V, Stray S, Lipschitz DA, Cook JD, Pippard MJ, et al. Plasma ferritin determination as a diagnostic tool. West J Med 1986; 145:657-663. (Pubitemid 17196113)
39. Mast AE, Blinder MA, Gronowski AM, Chumley C, Scott MG. Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clin Chem 1998; 44:45-51. (Pubitemid 28042465)
40. Hansen TM, Hansen NE. Serum ferritin as indicator of iron responsive anaemia in patients with rheumatoid arthritis. Ann Rheum Dis 1986; 45:596-602. (Pubitemid 16066086)
41. Witte DL, Kraemer DF, Johnson GF, Dick FR, Hamilton H. Prediction of bone marrow iron findings from tests performed on peripheral blood. Am J Clin Pathol 1986; 82:202-206. (Pubitemid 16167120)
42. Witte DL, Angstadt DS, Davis SH, Schrantz RD. Predicting bone marrow iron stores in anemic patients in a community hospital using ferritin and erythrocyte sedimentation rate. Am J Clin Pathol 1988; 90:85-87.
43. Coenen JLLM, Van Dieijen-Visser MP, Van Pelt K, Van Deursen CTBM, Fickers MMF, VanWersch JWJ, et al. Measurements of serum ferritin used to predict concentrations of iron in bone marrow in anemia of chronic disease. Clin Chem 1991; 37:560-563. (Pubitemid 21892692)
44. Kurer SB, Seifert B, Michel B, Ruegg R, Fehr J. Prediction of iron deficiency in chronic inflammatory rheumatic disease anaemia. Br J Haematol 1995; 91:820-826.
45. Punnonen K, Irjala K, Rajamaki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood 1997; 89:1052-1057. (Pubitemid 27121300)
46. Junca J, Fernandez-Aviles F, Oriol A, Navarro JT, Milla F, Sancho JM, et al. The usefulness of the serum transferrin receptor in detecting iron deficiency in the anemia of chronic disorders. Haematologica 1998; 83:676-680. (Pubitemid 28492146)
47. North M, Dallalio G, Donath AS, Metlink R, Means RT Jr. Serum transferring receptor levels in patients undergoing evaluation of iron stores: correlation with other parameters and observed versus predicted results. Clin Lab Haem 1997; 19:93-97. (Pubitemid 27286909)
48. American Gastroenterological Association. AGA medical position statement: evaluation and management of occult and obscure gastrointestinal bleeding. Gastroenterology 2000; 118:197-200.
49. Zukerman G, Benitez J. A prospective study of bidirectional endoscopy (colonoscopy and upper endoscopy) in the evaluation of patients with occult gastrointestinal bleeding. Am J Gastroenterol 1992; 87:62-66.
50. Hopper AD, Leeds JS, Hurlstone DP, Hadjivassiliou M, Drew K, Sanders DS. Are lower gastrointestinal investigations necessary in patients with celiac disease? Eur J Gastroenterol Hepatol 2005; 17:617-621. (Pubitemid 40733808)
51. Green BT, Rockey DC. Gastrointestinal endoscopic evaluation of premenopausal women with iron deficiency anemia. J Clin Gastroenterol 2004; 38:104-109. (Pubitemid 38134146)
52. Carter D, Maor Y, Bar-Meir S, Avidan B. Prevalence and predictive signs for gastrointestinal lesions in premenopausal women with iron deficiency anemia. Dig Dis Sci 2008; 53:3138-3144.
53. Park DI, Ryu SH, Oh SJ, Yoo TW, Kim HJ, Cho YK, et al. Significance of endoscopy in asymptomatic premenopausal women with iron deficiency anemia. Dig Dis Sci 2006; 51:2372-2376.
54. Bini EJ, Micale PL, Weinshel EH. Evaluation of the gastrointestinal tract in premenopausal women with iron deficiency anemia. Am J Med 1998; 105:281-286. (Pubitemid 28487535)
55. Powell N, NcNair A. Gastrointestinal evaluation of anaemic patients without evidence of iron deficiency. Eur J Gastroenterol Hepatol 2008; 20:1094-1100.
56. Sawhney MS, Lipato T, Nelson DB, Lederle FA, Rector TS, Bond JH. Should patients with anemia and low normal or normal serum ferritin undergo colonoscopy? Am J Gastroenterol 2007; 102:82-88. (Pubitemid 46072046)
57. Wang SA, Fadare O, Nagar A, Shafi NQ, Rose MG. Gastrointestinal endoscopic findings in men with unexplained anemia and low normal ferritin values. Am J Hematol 2006; 81:324-327.
58. Raju GS, Gerson L, Das A, Lewis B. American gastroenterological association (AGA) institute technical review on obscure gastrointestinal bleeding. Gastroenterology 2007; 133:1697-1717. (Pubitemid 350029731)
59. Liao Z, Gao R, Xu C, Li ZS. Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: A systematic review. Gastrointest Endosc 2010; 71:280-286.
60. Fireman Z, Kopelman Y. The role of video capsule endoscopy in the evaluation of iron deficiency anaemia. Dig Liver Dis 2004; 36:97-102. (Pubitemid 41115500)
61. Mazzarolo S, Brady P. Small bowel capsule endoscopy: A systematic review. Southern Med J 2007; 100:274-280. (Pubitemid 46673428)
62. Treister SL, Leighton JA, Leontiadis GI, Fleischer DE, Hara AK, Heigh RI, et al. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with obscure gastrointestinal bleeding. Am J Gastroenterol 2005; 100:2407-2418.
63. Lewis BS, Eisen GM, Friedman S. A pooled analysis to evaluate results of capsule endoscopy trials. Endoscopy 2005; 37:960-965 (Pubitemid 41489265)
64. Pasha SF, Leighton JA, Leontiadis GI, Das A, Harrison ME, Decker G, et al. Double-balloon enteroscopy and capsule endoscopy have comparable diagnostic yield in small-bowel disease: A meta-analysis. Clin Gastroenterol Hepatol 2008; 6:671-676.
65. Arakawa D, Ohmiya N, Nakamura M, Honda W, Shirai O, Itoh A, et al. Outcome after enteroscopy for patients with obscure GI bleeding: diagnostic comparison between double-balloon endoscopy and videocapsule endoscopy. Gastrointest Endosc 2009; 69:866-874.
66. Li X, Dai J, Lu H, Gao Y, Chen H, Ge Z. A prospective study on evaluating the diagnostic yield of video capsule endoscopy followed by directed double-balloon enteroscopy in patients with obscure gastrointestinal bleeding. Dig Dis Sci 2010; 55:1704-1710.
67. Nakamura M, Niwa Y, Ohmiya N, Miyahara R, Ohashi A, Itoh A, et al. Preliminary comparison of capsule endoscopy and double-balloon enteroscopy in patients with suspected small-bowel bleeding. Endoscopy 2006; 38:59-66. (Pubitemid 43092705)
68. Kaffes AJ, Siah C, Koo JH. Clinical outcomes after double-balloon enteroscopy in patients with obscure GI bleeding and a positive capsule endoscopy. Gastrointest Endosc 2007; 66:304-309. (Pubitemid 47069297)
69. Zaman A, Katon RM. Push enteroscopy for obscure gastrointestinal bleeding yields a high incidence of proximal lesions within reach of a standard endoscope. Gastrointest Endosc 1998; 47:372-376. (Pubitemid 28237507)
70. Descamps C, Schmit A, Van Gossum A. "Missed" upper gastrointestinal tract lesions may explain "occult" bleeding. Endoscopy 1999; 31:452-455. (Pubitemid 29412574)
71. Chak A, Cooper GS, Cnato MI, Pollack BJ, Sivak MV Jr. Enteroscopy for the initial evaluation of iron deficiency. Gastrointest Endosc 1998; 47:144-148. (Pubitemid 28096157)
72. Landi B, Tkoub M, Gaudric M, Guimbaud R, Cervoni JP, Chaussade S, et al. Diagnostic yield of push-type enteroscopy in relation to indication. Gut 1998; 42:421-425. (Pubitemid 28197035)
73. Fry LC, Bellutti M, Neumann P, Malfertheiner P, Monkemuller K. Incidence of bleeding lesions within reach of conventional upper and lower endoscopes in patients undergoing double-balloon enteroscopy for obscure gastrointestinal bleeding. Aliment Pharmacol Ther 2009; 29:342-349.
74. Tee HP, Kaffes AJ. Non-small-bowel lesions encountered during doubleballoon enteroscopy performed for obscure gastrointestinal bleeding. World J Gastroenterol 2010; 16:1885-1889.
75. Gilbert D, O'Malley S, Selby W. Are repeat upper gastrointestinal endoscopy and colonoscopy necessary within six months of capsule endoscopy in patients with obscure gastrointestinal bleeding? J Gastroenterol Hepatol 2008; 23:1806-1809.
76. Costamagna G, Shah SK, Riccioni ME, Foschia F, Mutignani M, Perri V, et al. A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease. Gastroenterology 2002; 123:999-1005.
77. Malik A, Lukaszewski K, Caroline D, Parkman H, DeSpiro J, Banson F, et al. A retrospective review of enteroclysis in patients with obscure gastrointestinal bleeding and chronic abdominal pain of undetermined etiology. Dig Dis Sci 2005; 50:649-655. (Pubitemid 40558455)
78. Hallberg L, Brune M, Rossander-Hulthen L. Is there a physiological role of vitamin C in iron absorption? Ann N Y Acad Sci 1987; 498:324-332.
79. Buetler E. Disorders of iron metabolism. In: Lichtman MA, Beutler E, Kaushansky K, Kipps TJ, Seligsohn U, Prchal J, editors. Williams hematology. 7th ed. New York: McGraw-Hill; 2006. pp. 511-553.
80. Rimon E, Kagansky N, Kagansky M, Mechnick L, Mashiah T, Namir M, et al. Are we giving too much iron? Low-dose iron therapy is effective in octogenarians. Am J Med 2005; 118:1142-1147. (Pubitemid 41363767)
81. Zhou SJ, Gibson RA, Crowther CA, Makrides M. Should we lower the dose of iron when treating anaemia in pregnancy? A randomized doseresponse trial. Eur J Clin Nutr 2009; 63:183-190.
82. Walker SE, Paton TW, Cowan DH, Manuel MA, Dranitsaris G. Bioavailability of iron in oral ferrous sulfate preparations in healthy volunteers. Can Med Assoc J 1989; 141:543-547. (Pubitemid 19238992)
83. Brittenham GM. Chapter 36 - Disorders of iron metabolism: iron deficiency and iron overload. In: Hoffman R, Benz E, Shattil S, Furie B, Silberstein L, McGlave P, editors. Hematology: Basic principles and practice. 5th ed. Philadelphia PA: Elsevier; p. 459.
84. Auerbach M, Ballard H. Clinical use of intravenous iron: Administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program 2010; 2010:338-347.
85. Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmen J. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant 2006; 21:378-382. (Pubitemid 43159991)
86. Johnson-Wimbley TD, Graham DY. Diagnosis and management of iron deficiency anemia in the 21st century. Ther Adv Gastroenterol 2011; 4:177-184.
87. Grey DE, Finlayson J. Red cell transfusion for iron-deficiency anaemia: A retrospective audit at a tertiary hospital. Vox Sang 2008; 94:138-142.