Anemia and iron deficiency in gastrointestinal and liver conditions

Jürgen Stein, Susan Connor, Garth Virgin, David Eng Hui Ong, Lisandro Pereyra, Jürgen Stein, Susan Connor, Garth Virgin, David Eng Hui Ong, Lisandro Pereyra

Abstract

Iron deficiency anemia (IDA) is associated with a number of pathological gastrointestinal conditions other than inflammatory bowel disease, and also with liver disorders. Different factors such as chronic bleeding, malabsorption and inflammation may contribute to IDA. Although patients with symptoms of anemia are frequently referred to gastroenterologists, the approach to diagnosis and selection of treatment as well as follow-up measures is not standardized and suboptimal. Iron deficiency, even without anemia, can substantially impact physical and cognitive function and reduce quality of life. Therefore, regular iron status assessment and awareness of the clinical consequences of impaired iron status are critical. While the range of options for treatment of IDA is increasing due to the availability of effective and well-tolerated parenteral iron preparations, a comprehensive overview of IDA and its therapy in patients with gastrointestinal conditions is currently lacking. Furthermore, definitions and assessment of iron status lack harmonization and there is a paucity of expert guidelines on this topic. This review summarizes current thinking concerning IDA as a common co-morbidity in specific gastrointestinal and liver disorders, and thus encourages a more unified treatment approach to anemia and iron deficiency, while offering gastroenterologists guidance on treatment options for IDA in everyday clinical practice.

Keywords: Bariatric surgery; Celiac disease; Chronic hepatitis; Gastritis; Gastrointestinal bleeding; Gastrointestinal neoplasm; Infection; Iron deficiency anemia; Non-alcoholic fatty liver disease; Nonsteroidal anti-inflammatory drugs.

Conflict of interest statement

Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

Figures

Figure 1
Figure 1
Pathogenic mechanisms proposed to be involved in the association of iron deficiency anemia and Helicobacter pylori infection[63].
Figure 2
Figure 2
Role of iron in essential cellular functions[178].
Figure 3
Figure 3
Suggested approach for the assessment and treatment of iron deficiency/iron deficiency anemia in clinical practice. 1In patients with inflammation, ferritin levels < 100 ng/mL should be considered as iron-deficient; 2Hb increase < 2 g/dL in 4 wk. Stein et al[6]. CHr: Hemoglobin content of reticulocytes; CRP: C-reactive protein; ESA: Erythropoiesis-stimulating agent; Hb: Hemoglobin; %HYPO: Percent hypochromic red blood cells; ID: Iron deficiency; IDA: Iron deficiency anemia; TSAT: Transferrin saturation.

References

    1. Goddard AF, James MW, McIntyre AS, Scott BB. Guidelines for the management of iron deficiency anaemia. Gut. 2011;60:1309–1316.
    1. Luman W, Ng KL. Audit of investigations in patients with iron deficiency anaemia. Singapore Med J. 2003;44:504–510.
    1. Marignani M, Angeletti S, Filippi L, Danieli R, Schillaci O. Occult and obscure bleeding, iron deficiency anemia and other gastrointestinal stories (Review) Int J Mol Med. 2005;15:129–135.
    1. Bayraktar UD, Bayraktar S. Treatment of iron deficiency anemia associated with gastrointestinal tract diseases. World J Gastroenterol. 2010;16:2720–2725.
    1. Zhu A, Kaneshiro M, Kaunitz JD. Evaluation and treatment of iron deficiency anemia: a gastroenterological perspective. Dig Dis Sci. 2010;55:548–559.
    1. Stein J, Hartmann F, Dignass AU. Diagnosis and management of iron deficiency anemia in patients with IBD. Nat Rev Gastroenterol Hepatol. 2010;7:599–610.
    1. Gasche C, Berstad A, Befrits R, Beglinger C, Dignass A, Erichsen K, Gomollon F, Hjortswang H, Koutroubakis I, Kulnigg S, et al. Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Inflamm Bowel Dis. 2007;13:1545–1553.
    1. Dignass AU, Gasche C, Bettenworth D, Birgegård G, Danese S, Gisbert JP, Gomollon F, Iqbal T, Katsanos K, Koutroubakis I, et al. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. J Crohns Colitis. 2015;9:211–222.
    1. Bager P, Dahlerup JF. Randomised clinical trial: oral vs. intravenous iron after upper gastrointestinal haemorrhage--a placebo-controlled study. Aliment Pharmacol Ther. 2014;39:176–187.
    1. Fernández-Bañares F, Monzón H, Forné M. A short review of malabsorption and anemia. World J Gastroenterol. 2009;15:4644–4652.
    1. Gomollón F, Gisbert JP. Anemia and inflammatory bowel diseases. World J Gastroenterol. 2009;15:4659–4665.
    1. Niv E, Elis A, Zissin R, Naftali T, Novis B, Lishner M. Iron deficiency anemia in patients without gastrointestinal symptoms--a prospective study. Fam Pract. 2005;22:58–61.
    1. Patterson RN, Johnston SD. Iron deficiency anaemia: are the British Society of Gastroenterology guidelines being adhered to? Postgrad Med J. 2003;79:226–228.
    1. Busti F, Campostrini N, Martinelli N, Girelli D. Iron deficiency in the elderly population, revisited in the hepcidin era. Front Pharmacol. 2014;5:83.
    1. Dharmarajan TS, Bullecer MLF, Pitchumoni CS. Anemia of gastrointestinal origin in the elderly. Pract Gastroenterol. 2015;26:22–36.
    1. Ferguson A, Brydon WG, Brian H, Williams A, Mackie MJ. Use of whole gut perfusion to investigate gastrointestinal blood loss in patients with iron deficiency anaemia. Gut. 1996;38:120–124.
    1. Stein J, Dignass AU. Anaemia in the Elderly IBD Patient. Curr Treat Options Gastroenterol. 2015;13:308–318.
    1. Geisel T, Martin J, Schulze B, Schaefer R, Bach M, Virgin G, Stein J. An etiologic profile of anemia in 405 geriatric patients. Anemia. 2014;2014:932486.
    1. Gomollón F, Gisbert JP, García-Erce JA. Intravenous iron in digestive diseases: a clinical (re)view. Ther Adv Chronic Dis. 2010;1:67–75.
    1. Koch TA, Myers J, Goodnough LT. Intravenous Iron Therapy in Patients with Iron Deficiency Anemia: Dosing Considerations. Anemia. 2015;2015:763576.
    1. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372:1832–1843.
    1. Lopez A, Cacoub P, Macdougall IC, Peyrin-Biroulet L. Iron deficiency anaemia. Lancet. 2016;387:907–916.
    1. Cameron AJ. Incidence of iron deficiency anemia in patients with large diaphragmatic hernia. A controlled study. Mayo Clin Proc. 1976;51:767–769.
    1. Cameron AJ, Higgins JA. Linear gastric erosion. A lesion associated with large diaphragmatic hernia and chronic blood loss anemia. Gastroenterology. 1986;91:338–342.
    1. Carrott PW, Markar SR, Hong J, Kuppusamy MK, Koehler RP, Low DE. Iron-deficiency anemia is a common presenting issue with giant paraesophageal hernia and resolves following repair. J Gastrointest Surg. 2013;17:858–862.
    1. Panzuto F, Di Giulio E, Capurso G, Baccini F, D’Ambra G, Delle Fave G, Annibale B. Large hiatal hernia in patients with iron deficiency anaemia: a prospective study on prevalence and treatment. Aliment Pharmacol Ther. 2004;19:663–670.
    1. Ruhl CE, Everhart JE. Relationship of iron-deficiency anemia with esophagitis and hiatal hernia: hospital findings from a prospective, population-based study. Am J Gastroenterol. 2001;96:322–326.
    1. Crooks CJ, West J, Card TR. Upper gastrointestinal haemorrhage and deprivation: a nationwide cohort study of health inequality in hospital admissions. Gut. 2012;61:514–520.
    1. Gralnek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. N Engl J Med. 2008;359:928–937.
    1. Jairath V, Kahan BC, Logan RF, Hearnshaw SA, Travis SP, Murphy MF, Palmer KR. Mortality from acute upper gastrointestinal bleeding in the United kingdom: does it display a “weekend effect”? Am J Gastroenterol. 2011;106:1621–1628.
    1. Barkun AN, Bardou M, Kuipers EJ, Sung J, Hunt RH, Martel M, Sinclair P. International consensus recommendations on the management of patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med. 2010;152:101–113.
    1. British Society of Gastroenterology Endoscopy Committee. Non-variceal upper gastrointestinal haemorrhage: guidelines. Gut. 2002;51 Suppl 4:iv1–iv6.
    1. Bager P, Dahlerup JF. Lack of follow-up of anaemia after discharge from an upper gastrointestinal bleeding centre. Dan Med J. 2013;60:A4583.
    1. Rockall TA, Logan RF, Devlin HB, Northfield TC. Risk assessment after acute upper gastrointestinal haemorrhage. Gut. 1996;38:316–321.
    1. Jairath V, Kahan BC, Gray A, Doré CJ, Mora A, James MW, Stanley AJ, Everett SM, Bailey AA, Dallal H, et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386:137–144.
    1. Villanueva C. Gastrointestinal bleeding: Blood transfusion for acute upper gastrointestinal bleeding. Nat Rev Gastroenterol Hepatol. 2015;12:432–434.
    1. Fortun PJ, Hawkey CJ. Nonsteroidal antiinflammatory drugs and the small intestine. Curr Opin Gastroenterol. 2007;23:134–141.
    1. Hernández-Díaz S, Rodríguez LA. Association between nonsteroidal anti-inflammatory drugs and upper gastrointestinal tract bleeding/perforation: an overview of epidemiologic studies published in the 1990s. Arch Intern Med. 2000;160:2093–2099.
    1. Laine L, Smith R, Min K, Chen C, Dubois RW. Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther. 2006;24:751–767.
    1. Graham DY, Opekun AR, Willingham FF, Qureshi WA. Visible small-intestinal mucosal injury in chronic NSAID users. Clin Gastroenterol Hepatol. 2005;3:55–59.
    1. Maiden L, Thjodleifsson B, Theodors A, Gonzalez J, Bjarnason I. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005;128:1172–1178.
    1. Moore RA, Derry S, McQuay HJ. Faecal blood loss with aspirin, nonsteroidal anti-inflammatory drugs and cyclo-oxygenase-2 selective inhibitors: systematic review of randomized trials using autologous chromium-labelled erythrocytes. Arthritis Res Ther. 2008;10:R7.
    1. Lanas A, García-Rodríguez LA, Arroyo MT, Gomollón F, Feu F, González-Pérez A, Zapata E, Bástida G, Rodrigo L, Santolaria S, et al. Risk of upper gastrointestinal ulcer bleeding associated with selective cyclo-oxygenase-2 inhibitors, traditional non-aspirin non-steroidal anti-inflammatory drugs, aspirin and combinations. Gut. 2006;55:1731–1738.
    1. Mamdani M, Rochon PA, Juurlink DN, Kopp A, Anderson GM, Naglie G, Austin PC, Laupacis A. Observational study of upper gastrointestinal haemorrhage in elderly patients given selective cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs. BMJ. 2002;325:624.
    1. Toyoda H, Tanabe N, Toyoda M, Toyoda N, Takei Y. Effect of the misoprostol-rebamipide combination on iron deficiency anemia in patients under long-term cyclooxygenase-2 selective inhibitor treatment for small bowel ulcers. Clin J Gastroenterol. 2012;5:155–157.
    1. Goldstein JL, Eisen GM, Lewis B, Gralnek IM, Zlotnick S, Fort JG. Video capsule endoscopy to prospectively assess small bowel injury with celecoxib, naproxen plus omeprazole, and placebo. Clin Gastroenterol Hepatol. 2005;3:133–141.
    1. Selinger CP, Ang YS. Gastric antral vascular ectasia (GAVE): an update on clinical presentation, pathophysiology and treatment. Digestion. 2008;77:131–137.
    1. Nguyen H, Le C, Nguyen H. Gastric antral vascular ectasia (watermelon stomach)-an enigmatic and often-overlooked cause of gastrointestinal bleeding in the elderly. Perm J. 2009;13:46–49.
    1. Johnson J, Derk CT. Gastric antral vascular ectasia in systemic sclerosis. Int J Rheumatol. 2011;2011:305238.
    1. Schouten JN, Verheij J, Seijo S. Idiopathic non-cirrhotic portal hypertension: a review. Orphanet J Rare Dis. 2015;10:67.
    1. Patwardhan VR, Cardenas A. Review article: the management of portal hypertensive gastropathy and gastric antral vascular ectasia in cirrhosis. Aliment Pharmacol Ther. 2014;40:354–362.
    1. Ripoll C, Garcia-Tsao G. Management of gastropathy and gastric vascular ectasia in portal hypertension. Clin Liver Dis. 2010;14:281–295.
    1. Ripoll C, Garcia-Tsao G. The management of portal hypertensive gastropathy and gastric antral vascular ectasia. Dig Liver Dis. 2011;43:345–351.
    1. RIDER JA, KLOTZ AP, KIRSNER JB. Gastritis with veno-capillary ectasia as a source of massive gastric hemorrhage. Gastroenterology. 1953;24:118–123.
    1. Ghrénassia E, Avouac J, Khanna D, Derk CT, Distler O, Suliman YA, Airo P, Carreira PE, Foti R, Granel B, et al. Prevalence, correlates and outcomes of gastric antral vascular ectasia in systemic sclerosis: a EUSTAR case-control study. J Rheumatol. 2014;41:99–105.
    1. Dulai GS, Jensen DM, Kovacs TO, Gralnek IM, Jutabha R. Endoscopic treatment outcomes in watermelon stomach patients with and without portal hypertension. Endoscopy. 2004;36:68–72.
    1. Hershko C, Camaschella C. How I treat unexplained refractory iron deficiency anemia. Blood. 2014;123:326–333.
    1. Dickey W, Kenny BD, McMillan SA, Porter KG, McConnell JB. Gastric as well as duodenal biopsies may be useful in the investigation of iron deficiency anaemia. Scand J Gastroenterol. 1997;32:469–472.
    1. Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis--pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10:529–541.
    1. Betesh AL, Santa Ana CA, Cole JA, Fordtran JS. Is achlorhydria a cause of iron deficiency anemia? Am J Clin Nutr. 2015;102:9–19.
    1. Hershko C, Ronson A, Souroujon M, Maschler I, Heyd J, Patz J. Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. Blood. 2006;107:1673–1679.
    1. Hershko C, Ronson A. Iron deficiency, Helicobacter infection and gastritis. Acta Haematol. 2009;122:97–102.
    1. Franceschi F, Zuccalà G, Roccarina D, Gasbarrini A. Clinical effects of Helicobacter pylori outside the stomach. Nat Rev Gastroenterol Hepatol. 2014;11:234–242.
    1. Muhsen K, Cohen D. Helicobacter pylori infection and iron stores: a systematic review and meta-analysis. Helicobacter. 2008;13:323–340.
    1. Yuan W, Li Yumin D, Yang L. Iron deficiency anemia in Helicobacter pylori infection: meta-analysis of randomized controlled trials. Scand J Gastroenterol. 2010;45:665–676.
    1. Malfertheiner P, Megraud F, O’Morain CA, Atherton J, Axon AT, Bazzoli F, Gensini GF, Gisbert JP, Graham DY, Rokkas T, et al. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut. 2012;61:646–664.
    1. Asaka M, Kato M, Takahashi S, Fukuda Y, Sugiyama T, Ota H, Uemura N, Murakami K, Satoh K, Sugano K. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter. 2010;15:1–20.
    1. Fischbach W, Malfertheiner P, Hoffmann JC, Bolten W, Bornschein J, Götze O, Höhne W, Kist M, Koletzko S, Labenz J, et al. S3-guideline “helicobacter pylori and gastroduodenal ulcer disease” of the German society for digestive and metabolic diseases (DGVS) in cooperation with the German society for hygiene and microbiology, society for pediatric gastroenterology and nutrition e. V., German society for rheumatology, AWMF-registration-no. 021 / 001. Z Gastroenterol. 2009;47:1230–1263.
    1. Fock KM, Talley N, Moayyedi P, Hunt R, Azuma T, Sugano K, Xiao SD, Lam SK, Goh KL, Chiba T, et al. Asia-Pacific consensus guidelines on gastric cancer prevention. J Gastroenterol Hepatol. 2008;23:351–365.
    1. Emiralioglu N, Yenicesu I, Sari S, Egritas O, Poyraz A, Pasaoglu OT, Celik B, Dalgic B. An insight into the relationships between prohepcidin, iron deficiency anemia, and interleukin-6 values in pediatric Helicobacter pylori gastritis. Eur J Pediatr. 2015;174:903–910.
    1. Sato Y, Yoneyama O, Azumaya M, Takeuchi M, Sasaki SY, Yokoyama J, Shioji K, Kawauchi Y, Hashimoto S, Nishigaki Y, et al. The relationship between iron deficiency in patients with Helicobacter pylori-infected nodular gastritis and the serum prohepcidin level. Helicobacter. 2015;20:11–18.
    1. Azab SF, Esh AM. Serum hepcidin levels in Helicobacter pylori-infected children with iron-deficiency anemia: a case-control study. Ann Hematol. 2013;92:1477–1483.
    1. Yokota S, Konno M, Mino E, Sato K, Takahashi M, Fujii N. Enhanced Fe ion-uptake activity in Helicobacter pylori strains isolated from patients with iron-deficiency anemia. Clin Infect Dis. 2008;46:e31–e33.
    1. Noto JM, Gaddy JA, Lee JY, Piazuelo MB, Friedman DB, Colvin DC, Romero-Gallo J, Suarez G, Loh J, Slaughter JC, et al. Iron deficiency accelerates Helicobacter pylori-induced carcinogenesis in rodents and humans. J Clin Invest. 2013;123:479–492.
    1. Noto JM, Lee JY, Gaddy JA, Cover TL, Amieva MR, Peek RM. Regulation of Helicobacter pylori Virulence Within the Context of Iron Deficiency. J Infect Dis. 2015;211:1790–1794.
    1. Yamaoka Y. Mechanisms of disease: Helicobacter pylori virulence factors. Nat Rev Gastroenterol Hepatol. 2010;7:629–641.
    1. Stein J, Stier C, Raab H, Weiner R. Review article: The nutritional and pharmacological consequences of obesity surgery. Aliment Pharmacol Ther. 2014;40:582–609.
    1. Aills L, Blankenship J, Buffington C, Furtado M, Parrott J. ASMBS Allied Health Nutritional Guidelines for the Surgical Weight Loss Patient. Surg Obes Relat Dis. 2008;4:S73–108.
    1. Love AL, Billett HH. Obesity, bariatric surgery, and iron deficiency: true, true, true and related. Am J Hematol. 2008;83:403–409.
    1. ten Broeke R, Bravenboer B, Smulders FJ. Iron deficiency before and after bariatric surgery: the need for iron supplementation. Neth J Med. 2013;71:412–417.
    1. Obinwanne KM, Fredrickson KA, Mathiason MA, Kallies KJ, Farnen JP, Kothari SN. Incidence, treatment, and outcomes of iron deficiency after laparoscopic Roux-en-Y gastric bypass: a 10-year analysis. J Am Coll Surg. 2014;218:246–252.
    1. Alexandrou A, Armeni E, Kouskouni E, Tsoka E, Diamantis T, Lambrinoudaki I. Cross-sectional long-term micronutrient deficiencies after sleeve gastrectomy versus Roux-en-Y gastric bypass: a pilot study. Surg Obes Relat Dis. 2014;10:262–268.
    1. Apovian CM, Cummings S, Anderson W, Borud L, Boyer K, Day K, Hatchigian E, Hodges B, Patti ME, Pettus M, et al. Best practice updates for multidisciplinary care in weight loss surgery. Obesity (Silver Spring) 2009;17:871–879.
    1. Malone M, Barish C, He A, Bregman D. Comparative review of the safety and efficacy of ferric carboxymaltose versus standard medical care for the treatment of iron deficiency anemia in bariatric and gastric surgery patients. Obes Surg. 2013;23:1413–1420.
    1. Godfrey JD, Brantner TL, Brinjikji W, Christensen KN, Brogan DL, Van Dyke CT, Lahr BD, Larson JJ, Rubio-Tapia A, Melton LJ, et al. Morbidity and mortality among older individuals with undiagnosed celiac disease. Gastroenterology. 2010;139:763–769.
    1. Çekın AH, Çekın Y, Sezer C. Celiac disease prevalence in patients with iron deficiency anemia. Turk J Gastroenterol. 2012;23:490–495.
    1. Unsworth DJ, Lock FJ, Harvey RF. Iron-deficiency anaemia in premenopausal women. Lancet. 1999;353:1100.
    1. Volta U, Caio G, Stanghellini V, De Giorgio R. The changing clinical profile of celiac disease: a 15-year experience (1998-2012) in an Italian referral center. BMC Gastroenterol. 2014;14:194.
    1. Wierdsma NJ, van Bokhorst-de van der Schueren MA, Berkenpas M, Mulder CJ, van Bodegraven AA. Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients. Nutrients. 2013;5:3975–3992.
    1. Corazza GR, Valentini RA, Andreani ML, D’Anchino M, Leva MT, Ginaldi L, De Feudis L, Quaglino D, Gasbarrini G. Subclinical coeliac disease is a frequent cause of iron-deficiency anaemia. Scand J Gastroenterol. 1995;30:153–156.
    1. Howard MR, Turnbull AJ, Morley P, Hollier P, Webb R, Clarke A. A prospective study of the prevalence of undiagnosed coeliac disease in laboratory defined iron and folate deficiency. J Clin Pathol. 2002;55:754–757.
    1. Hershko C, Patz J. Ironing out the mechanism of anemia in celiac disease. Haematologica. 2008;93:1761–1765.
    1. Fine KD. The prevalence of occult gastrointestinal bleeding in celiac sprue. N Engl J Med. 1996;334:1163–1167.
    1. Martin J, Geisel T, Maresch C, Krieger K, Stein J. Inadequate nutrient intake in patients with celiac disease: results from a German dietary survey. Digestion. 2013;87:240–246.
    1. Harper JW, Holleran SF, Ramakrishnan R, Bhagat G, Green PH. Anemia in celiac disease is multifactorial in etiology. Am J Hematol. 2007;82:996–1000.
    1. Maslovsky I. Intravenous iron in a primary-care clinic. Am J Hematol. 2005;78:261–264.
    1. Annibale B, Severi C, Chistolini A, Antonelli G, Lahner E, Marcheggiano A, Iannoni C, Monarca B, Delle FG. Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients. Am J Gastroenterol. 2001;96:132–137.
    1. Vici G, Belli L, Biondi M, Polzonetti V. Gluten free diet and nutrient deficiencies: A review. Clin Nutr. 2016 Epub ahead of print.
    1. Pironi L, Arends J, Baxter J, Bozzetti F, Peláez RB, Cuerda C, Forbes A, Gabe S, Gillanders L, Holst M, et al. ESPEN endorsed recommendations. Definition and classification of intestinal failure in adults. Clin Nutr. 2015;34:171–180.
    1. Kelly DA. Intestinal failure-associated liver disease: what do we know today? Gastroenterology. 2006;130:S70–S77.
    1. Ubesie AC, Kocoshis SA, Mezoff AG, Henderson CJ, Helmrath MA, Cole CR. Multiple micronutrient deficiencies among patients with intestinal failure during and after transition to enteral nutrition. J Pediatr. 2013;163:1692–1696.
    1. Yang CF, Duro D, Zurakowski D, Lee M, Jaksic T, Duggan C. High prevalence of multiple micronutrient deficiencies in children with intestinal failure: a longitudinal study. J Pediatr. 2011;159:39–44.e1.
    1. Khaodhiar L, Keane-Ellison M, Tawa NE, Thibault A, Burke PA, Bistrian BR. Iron deficiency anemia in patients receiving home total parenteral nutrition. JPEN J Parenter Enteral Nutr. 2002;26:114–119.
    1. Hwa YL, Rashtak S, Kelly DG, Murray JA. Iron Deficiency in Long-Term Parenteral Nutrition Therapy. JPEN J Parenter Enteral Nutr. 2016;40:869–876.
    1. Allwood MC, Martin H, Greenwood M, Maunder M. Precipitation of trace elements in parenteral nutrition mixtures. Clin Nutr. 1998;17:223–226.
    1. Robinson CA, Sawyer JE. Y-site compatibility of medications with parenteral nutrition. J Pediatr Pharmacol Ther. 2009;14:48–56.
    1. Beale AL, Penney MD, Allison MC. The prevalence of iron deficiency among patients presenting with colorectal cancer. Colorectal Dis. 2005;7:398–402.
    1. Ho CH, Yu YB, Wu PH. The prevalence of iron deficiency anemia and its clinical implications in patients with colorectal carcinoma. J Chin Med Assoc. 2008;71:119–122.
    1. Edna TH, Karlsen V, Jullumstrø E, Lydersen S. Prevalence of anaemia at diagnosis of colorectal cancer: assessment of associated risk factors. Hepatogastroenterology. 2012;59:713–716.
    1. Khanbhai M, Shah M, Cantanhede G, Ilyas S, Richards T. The problem of anaemia in patients with colorectal cancer. ISRN Hematol. 2014;2014:547914.
    1. Ludwig H, Müldür E, Endler G, Hübl W. Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol. 2013;24:1886–1892.
    1. Del Giudice ME, Vella ET, Hey A, Simunovic M, Harris W, Levitt C. Systematic review of clinical features of suspected colorectal cancer in primary care. Can Fam Physician. 2014;60:e405–e415.
    1. Wilkins T, Baird C, Pearson AN, Schade RR. Diverticular bleeding. Am Fam Physician. 2009;80:977–983.
    1. Cappell MS. The pathophysiology, clinical presentation, and diagnosis of colon cancer and adenomatous polyps. Med Clin North Am. 2005;89:1–42, vii.
    1. Judson I, Demetri G. Advances in the treatment of gastrointestinal stromal tumours. Ann Oncol. 2007;18 Suppl 10:x20–x24.
    1. Miettinen M, Lasota J. Gastrointestinal stromal tumors: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006;130:1466–1478.
    1. Kaemmer DA, Otto J, Lassay L, Steinau G, Klink C, Junge K, Klinge U, Schumpelick V. The Gist of literature on pediatric GIST: review of clinical presentation. J Pediatr Hematol Oncol. 2009;31:108–112.
    1. Duffaud F, Even C, Ray-Coquard I, Bompas E, Khoa-Huynh T, Salas S, Cassier P, Dufresne A, Bonvalot S, Ducimetiere F, et al. Recombinant erythropoietin for the anaemia of patients with advanced Gastrointestinal Stromal Tumours (GIST) receiving imatinib: an active agent only in non progressive patients. Clin Sarcoma Res. 2012;2:11.
    1. Sodergren SC, White A, Efficace F, Sprangers M, Fitzsimmons D, Bottomley A, Johnson CD. Systematic review of the side effects associated with tyrosine kinase inhibitors used in the treatment of gastrointestinal stromal tumours on behalf of the EORTC Quality of Life Group. Crit Rev Oncol Hematol. 2014;91:35–46.
    1. Vannella L, Lahner E, Osborn J, Annibale B. Systematic review: gastric cancer incidence in pernicious anaemia. Aliment Pharmacol Ther. 2013;37:375–382.
    1. Nakatani M, Fujiwara Y, Nagami Y, Sugimori S, Kameda N, Machida H, Okazaki H, Yamagami H, Tanigawa T, Watanabe K, et al. The usefulness of double-balloon enteroscopy in gastrointestinal stromal tumors of the small bowel with obscure gastrointestinal bleeding. Intern Med. 2012;51:2675–2682.
    1. Rosenberg PS, Alter BP, Ebell W. Cancer risks in Fanconi anemia: findings from the German Fanconi Anemia Registry. Haematologica. 2008;93:511–517.
    1. 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.
    1. Schmoll HJ, Van Cutsem E, Stein A, Valentini V, Glimelius B, Haustermans K, Nordlinger B, van de Velde CJ, Balmana J, Regula J, et al. ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. Ann Oncol. 2012;23:2479–2516.
    1. Association of Coloproctology of Great Britain and Ireland. Guidelines for the Management of Colorectal Cancer. [last accessed 15 Feb 2015] Available from:
    1. Scottish Intercollegiate Guidelines Network (SIGN) Diagnosis and management of colorectal cancer. Available from: .
    1. National Comprehensive Cancer Network Inc. NCCN Practice Guidelines in Oncology; Cancer and Chemotherapy-Induced Anemia - v.2.2015. Available from: .
    1. Edwards TJ, Noble EJ, Durran A, Mellor N, Hosie KB. Randomized clinical trial of preoperative intravenous iron sucrose to reduce blood transfusion in anaemic patients after colorectal cancer surgery. Br J Surg. 2009;96:1122–1128.
    1. Muñoz M, Gómez-Ramírez S, Martín-Montañez E, Auerbach M. Perioperative anemia management in colorectal cancer patients: a pragmatic approach. World J Gastroenterol. 2014;20:1972–1985.
    1. Amato A, Pescatori M. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane Database Syst Rev. 2006;(1):CD005033.
    1. Houbiers JG, van de Velde CJ, van de Watering LM, Hermans J, Schreuder S, Bijnen AB, Pahlplatz P, Schattenkerk ME, Wobbes T, de Vries JE, et al. Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: a prospective study. Transfusion. 1997;37:126–134.
    1. Schiergens TS, Rentsch M, Kasparek MS, Frenes K, Jauch KW, Thasler WE. Impact of perioperative allogeneic red blood cell transfusion on recurrence and overall survival after resection of colorectal liver metastases. Dis Colon Rectum. 2015;58:74–82.
    1. Shander A, Hofmann A, Ozawa S, Theusinger OM, Gombotz H, Spahn DR. Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion. 2010;50:753–765.
    1. Keeler BD, Simpson JA, Ng S, Tselepis C, Iqbal T, Brookes MJ, Acheson AG. The feasibility and clinical efficacy of intravenous iron administration for preoperative anaemia in patients with colorectal cancer. Colorectal Dis. 2014;16:794–800.
    1. Borstlap WA, Buskens CJ, Tytgat KM, Tuynman JB, Consten EC, Tolboom RC, Heuff G, van Geloven AA, van Wagensveld BA, C A Wientjes CA, et al. Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients. BMC Surg. 2015;15:78.
    1. Ranganathan P, Pramesh CS. Letter 1: Randomized clinical trial of preoperative intravenous iron sucrose to reduce blood transfusion in anaemic patients after colorectal cancer surgery (Br J Surg 2009; 96: 1122-1128) Br J Surg. 2010;97:297–298; author reply 299.
    1. Leal-Noval SR, Muñoz M, Asuero M, Contreras E, García-Erce JA, Llau JV, Moral V, Páramo JA, Quintana M. Spanish Consensus Statement on alternatives to allogeneic blood transfusion: the 2013 update of the “Seville Document”. Blood Transfus. 2013;11:585–610.
    1. Hallet J, Hanif A, Callum J, Pronina I, Wallace D, Yohanathan L, McLeod R, Coburn N. The impact of perioperative iron on the use of red blood cell transfusions in gastrointestinal surgery: a systematic review and meta-analysis. Transfus Med Rev. 2014;28:205–211.
    1. Azzam N, Aljebreen AM, Alharbi O, Almadi MA. Prevalence and clinical features of colonic diverticulosis in a Middle Eastern population. World J Gastrointest Endosc. 2013;5:391–397.
    1. World Gastroenterology Organisation. World Gastroenterology Organisation Practice Guidelines: Diverticular Disease. Available from: .
    1. Baxter NN. Emergency management of diverticulitis. Clin Colon Rectal Surg. 2004;17:177–182.
    1. Al-Onaizi I, Al-Awadi F, Al-Dawood AL. Iron deficiency anaemia: an unusual complication of Meckel’s diverticulum. Med Princ Pract. 2002;11:214–217.
    1. Sagar J, Kumar V, Shah DK. Meckel’s diverticulum: a systematic review. J R Soc Med. 2006;99:501–505.
    1. Kubo A, Kagaya T, Nakagawa H. Studies on complications of diverticular disease of the colon. Jpn J Med. 1985;24:39–43.
    1. Starke RD, Ferraro F, Paschalaki KE, Dryden NH, McKinnon TA, Sutton RE, Payne EM, Haskard DO, Hughes AD, Cutler DF, et al. Endothelial von Willebrand factor regulates angiogenesis. Blood. 2011;117:1071–1080.
    1. Holleran G, Hall B, Hussey M, McNamara D. Small bowel angiodysplasia and novel disease associations: a cohort study. Scand J Gastroenterol. 2013;48:433–438.
    1. Massyn MW, Khan SA. Heyde syndrome: a common diagnosis in older patients with severe aortic stenosis. Age Ageing. 2009;38:267–70; discussion 251.
    1. Aktas S, Kiyak M, Ozdil K, Kurtca I, Kibar S, Ahbab S, Karadeniz Y, Saler T. Gastrointestinal Tract Hemorrhage due to Angiodysplasia in Hutchinson Gilfort Progeria Syndrome. J Med Cases. 2013;4:576–578.
    1. Johnson-Wimbley TD, Graham DY. Diagnosis and management of iron deficiency anemia in the 21st century. Therap Adv Gastroenterol. 2011;4:177–184.
    1. Crompton DW, Nesheim MC. Nutritional impact of intestinal helminthiasis during the human life cycle. Annu Rev Nutr. 2002;22:35–59.
    1. Hesham MS, Edariah AB, Norhayati M. Intestinal parasitic infections and micronutrient deficiency: a review. Med J Malaysia. 2004;59:284–293.
    1. Kassebaum NJ, Bertozzi-Villa A, Coggeshall MS, Shackelford KA, Steiner C, Heuton KR, Gonzalez-Medina D, Barber R, Huynh C, Dicker D, et al. Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:980–1004.
    1. M’Koma AE, Wise PE, Schwartz DA, Muldoon RL, Herline AJ. Prevalence and outcome of anemia after restorative proctocolectomy: a clinical literature review. Dis Colon Rectum. 2009;52:726–739.
    1. Coull DB, Tait RC, Anderson JH, McKee RF, Finlay IG. Vitamin B12 deficiency following restorative proctocolectomy. Colorectal Dis. 2007;9:562–566.
    1. Gonzalez-Casas R, Jones EA, Moreno-Otero R. Spectrum of anemia associated with chronic liver disease. World J Gastroenterol. 2009;15:4653–4658.
    1. Hézode C. Management of anaemia and other treatment complications. Dig Liver Dis. 2013;45 Suppl 5:S337–S342.
    1. Ogawa E, Furusyo N, Nakamuta M, Kajiwara E, Nomura H, Dohmen K, Takahashi K, Satoh T, Azuma K, Kawano A, et al. Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy. J Hepatol. 2013;59:667–674.
    1. Zeuzem S, DeMasi R, Baldini A, Coate B, Luo D, Mrus J, Witek J. Risk factors predictive of anemia development during telaprevir plus peginterferon/ribavirin therapy in treatment-experienced patients. J Hepatol. 2014;60:1112–1117.
    1. Bacon BR, Gordon SC, Lawitz E, Marcellin P, Vierling JM, Zeuzem S, Poordad F, Goodman ZD, Sings HL, Boparai N, et al. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011;364:1207–1217.
    1. Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, et al. Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med. 2011;364:2405–2416.
    1. McHutchison JG, Manns MP, Muir AJ, Terrault NA, Jacobson IM, Afdhal NH, Heathcote EJ, Zeuzem S, Reesink HW, Garg J, et al. Telaprevir for previously treated chronic HCV infection. N Engl J Med. 2010;362:1292–1303.
    1. Sulkowski MS, Poordad F, Manns MP, Bronowicki JP, Rajender Reddy K, Harrison SA, Afdhal NH, Sings HL, Pedicone LD, Koury KJ, et al. Anemia during treatment with peginterferon Alfa-2b/ribavirin and boceprevir: Analysis from the serine protease inhibitor therapy 2 (SPRINT-2) trial. Hepatology. 2013;57:974–984.
    1. Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, Younossi Z, Foster GR, Horban A, et al. Telaprevir for retreatment of HCV infection. N Engl J Med. 2011;364:2417–2428.
    1. Mac Nicholas R, Norris S. Review article: optimizing SVR and management of the haematological side effects of peginterferon/ribavirin antiviral therapy for HCV - the role of epoetin, G-CSF and novel agents. Aliment Pharmacol Ther. 2010;31:929–937.
    1. Poordad F, Lawitz E, Reddy KR, Afdhal NH, Hézode C, Zeuzem S, Lee SS, Calleja JL, Brown RS, Craxi A, et al. Effects of ribavirin dose reduction vs erythropoietin for boceprevir-related anemia in patients with chronic hepatitis C virus genotype 1 infection--a randomized trial. Gastroenterology. 2013;145:1035–1044.e5.
    1. Romero-Gómez M, Berenguer M, Molina E, Calleja JL. Management of anemia induced by triple therapy in patients with chronic hepatitis C: challenges, opportunities and recommendations. J Hepatol. 2013;59:1323–1330.
    1. Clark PJ, Aghemo A, Degasperi E, Galmozzi E, Urban TJ, Vock DM, Patel K, Thompson AJ, Rumi MG, D’Ambrosio R, et al. Inosine triphosphatase deficiency helps predict anaemia, anaemia management and response in chronic hepatitis C therapy. J Viral Hepat. 2013;20:858–866.
    1. Jacobson IM, Kowdley KV, Kwo PY. Anemia management in the era of triple combination therapy for chronic HCV. Gastroenterol Hepatol (N Y) 2012;8:1–16.
    1. Maan R, van der Meer AJ, Brouwer WP, Plompen EP, Sonneveld MJ, Roomer R, van der Eijk AA, Groothuismink ZM, Hansen BE, Veldt BJ, et al. ITPA Polymorphisms Are Associated with Hematological Side Effects during Antiviral Therapy for Chronic HCV Infection. PLoS One. 2015;10:e0139317.
    1. Suwanthawornkul T, Anothaisintawee T, Sobhonslidsuk A, Thakkinstian A, Teerawattananon Y. Efficacy of Second Generation Direct-Acting Antiviral Agents for Treatment Naïve Hepatitis C Genotype 1: A Systematic Review and Network Meta-Analysis. PLoS One. 2015;10:e0145953.
    1. Siddique A, Nelson JE, Aouizerat B, Yeh MM, Kowdley KV. Iron deficiency in patients with nonalcoholic Fatty liver disease is associated with obesity, female gender, and low serum hepcidin. Clin Gastroenterol Hepatol. 2014;12:1170–1178.
    1. Ruivard M, Lainé F, Ganz T, Olbina G, Westerman M, Nemeth E, Rambeau M, Mazur A, Gerbaud L, Tournilhac V, et al. Iron absorption in dysmetabolic iron overload syndrome is decreased and correlates with increased plasma hepcidin. J Hepatol. 2009;50:1219–1225.
    1. Moya D, Baker SS, Liu W, Garrick M, Kozielski R, Baker RD, Zhu L. Novel pathway for iron deficiency in pediatric non-alcoholic steatohepatitis. Clin Nutr. 2015;34:549–556.
    1. Brownlie T, Utermohlen V, Hinton PS, Haas JD. Tissue iron deficiency without anemia impairs adaptation in endurance capacity after aerobic training in previously untrained women. Am J Clin Nutr. 2004;79:437–443.
    1. Favrat B, Balck K, Breymann C, Hedenus M, Keller T, Mezzacasa A, Gasche C. Evaluation of a single dose of ferric carboxymaltose in fatigued, iron-deficient women--PREFER a randomized, placebo-controlled study. PLoS One. 2014;9:e94217.
    1. Krayenbuehl PA, Battegay E, Breymann C, Furrer J, Schulthess G. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood. 2011;118:3222–3227.
    1. Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr. 2007;85:778–787.
    1. Jankowska EA, Von HS, Anker SD, Macdougall IC, Ponikowski P. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J. 2012;34:816–829.
    1. Evstatiev R, Gasche C. Iron sensing and signalling. Gut. 2012;61:933–952.
    1. Fillet G, Beguin Y, Baldelli L. Model of reticuloendothelial iron metabolism in humans: abnormal behavior in idiopathic hemochromatosis and in inflammation. Blood. 1989;74:844–851.
    1. Wish JB. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin J Am Soc Nephrol. 2006;1 Suppl 1:S4–S8.
    1. Stein J, Bager P, Befrits R, Gasche C, Gudehus M, Lerebours E, Magro F, Mearin F, Mitchell D, Oldenburg B, et al. Anaemia management in patients with inflammatory bowel disease: routine practice across nine European countries. Eur J Gastroenterol Hepatol. 2013;25:1456–1463.
    1. Geisser P, Burckhardt S. The pharmacokinetics and pharmacodynamics of iron preparations. Pharmaceutics. 2011;3:12–33.
    1. Goodnough LT, Maniatis A, Earnshaw P, Benoni G, Beris P, Bisbe E, Fergusson DA, Gombotz H, Habler O, Monk TG, et al. Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines. Br J Anaesth. 2011;106:13–22.
    1. Jumaa AK. Kidney disease: Improving global outcomes (KDIGO) anemia work group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int. 2012;2 Suppl:279–335.
    1. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2012;33:1787–1847.
    1. Qunibi WY. The efficacy and safety of current intravenous iron preparations for the management of iron-deficiency anaemia: a review. Arzneimittelforschung. 2010;60:399–412.
    1. Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmén J. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant. 2006;21:378–382.
    1. Yessayan L, Sandhu A, Besarab A, Yessayan A, Frinak S, Zasuwa G, Yee J. Intravenous iron dextran as a component of anemia management in chronic kidney disease: a report of safety and efficacy. Int J Nephrol. 2013;2013:703038.
    1. European Medicines Agency (EMA) Assessment report for: Iron containing intravenous (IV) medicinal products. Available from: .
    1. Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, Karnafel W, Garcia LC, Sambuelli AM, D’Haens G, Gasche C. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am J Gastroenterol. 2008;103:1182–1192.
    1. Evstatiev R, Marteau P, Iqbal T, Khalif IL, Stein J, Bokemeyer B, Chopey IV, Gutzwiller FS, Riopel L, Gasche C. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology. 2011;141:846–853.e1-2.
    1. Murphy GJ, Reeves BC, Rogers CA, Rizvi SI, Culliford L, Angelini GD. Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery. Circulation. 2007;116:2544–2552.
    1. Spahn DR, Moch H, Hofmann A, Isbister JP. Patient blood management: the pragmatic solution for the problems with blood transfusions. Anesthesiology. 2008;109:951–953.
    1. Taylor RW, O’Brien J, Trottier SJ, Manganaro L, Cytron M, Lesko MF, Arnzen K, Cappadoro C, Fu M, Plisco MS, et al. Red blood cell transfusions and nosocomial infections in critically ill patients. Crit Care Med. 2006;34:2302–238; quiz 2309.
    1. Ruz M, Carrasco F, Rojas P, Codoceo J, Inostroza J, Rebolledo A, Basfi-fer K, Csendes A, Papapietro K, Pizarro F, et al. Iron absorption and iron status are reduced after Roux-en-Y gastric bypass. Am J Clin Nutr. 2009;90:527–532.
    1. Laursen SB. Treatment and prognosis in peptic ulcer bleeding. Dan Med J. 2014;61:B4797.

Source: PubMed

3
Abonner