Pathogenesis, diagnosis and treatment of anaemia in immune-mediated gastrointestinal disorders
Corresponding Author
Gaetano Bergamaschi
Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
Correspondence: Gaetano Bergamaschi, Department of Internal Medicine, Fondazione I.R.C.C.S. Policlinico San Matteo, Piazzale Golgi, 27100 Pavia, Italy.
E-mail: [email protected]
Search for more papers by this authorAntonio Di Sabatino
Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
University of Pavia, Pavia, Italy
Search for more papers by this authorGino R. Corazza
Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
University of Pavia, Pavia, Italy
Search for more papers by this authorCorresponding Author
Gaetano Bergamaschi
Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
Correspondence: Gaetano Bergamaschi, Department of Internal Medicine, Fondazione I.R.C.C.S. Policlinico San Matteo, Piazzale Golgi, 27100 Pavia, Italy.
E-mail: [email protected]
Search for more papers by this authorAntonio Di Sabatino
Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
University of Pavia, Pavia, Italy
Search for more papers by this authorGino R. Corazza
Fondazione I.R.C.C.S. Policlinico San Matteo, Pavia, Italy
University of Pavia, Pavia, Italy
Search for more papers by this authorSummary
Immune-mediated disorders affecting the gastrointestinal (GI) tract may compromise GI integrity, interfere with the absorption of nutrients and cause bleeding and inflammation. All these features contribute to the pathogenesis of anaemia, the most prevalent extra-intestinal manifestation of immune-mediated GI disorders. Anaemia is most commonly due to iron deficiency and/or inflammation, but vitamin deficiencies and, more infrequently, autoimmune haemolysis or drug-induced myelosuppression can be involved. Here we address several issues related to the differential diagnosis and treatment of anaemia in immune-mediated GI disorders, giving particular relevance to the problem of iron deficiency anaemia associated with inflammation. It is emphasized how, in most cases, anaemias due to iron or vitamin deficiencies are best treated by parenteral administration of the deficient factor(s), and how the available high dose intravenous (IV) iron formulations can reduce ambulatory and social costs of IV iron supplementation, while improving patient's compliance to treatment. Actual and future treatment possibilities for anaemia of inflammation, involving the use of erythropoiesis stimulating agents, biologicals and hepcidin inhibitors are discussed.
References
- Abitbol, V., Borderie, D., Polin, V., Maksimovic, F., Sarfati, G., Esch, A., Tabouret, T., Dhooge, M., Dreanic, J., Perkins, G., Coriat, R. & Chaussade, S. (2015) Diagnosis of iron deficiency in inflammatory bowel disease by transferrin receptor-ferritin index. Medicine, 94, e1011.
- Andrès, E., Fothergill, H. & Mecili, M. (2010) Efficacy of oral cobalamin (vitamin B12) therapy. Expert Opinion on Pharmacotherapy, 11, 249–256.
- Anker, S.D., Comin Colet, J., Filippatos, G., Willenheimer, R., Dickstein, K., Drexler, H., Lüscher, T.F., Bart, B., Banasiak, W., Niegowska, J., Kirwan, B.A., Mori, C., von Eisenhart Rothe, B., Pocock, S.J., Poole-Wilson, P.A. & Ponikowski, P.; FAIR-HF Trial Investigators. (2009) Ferric carboxymaltose in patients with heart failure and iron deficiency. New England Journal of Medicine, 361, 2436–2448.
- Annibale, B., Severi, C., Chistolini, A., Antonelli, G., Lahner, E., Marcheggiano, A., Iannoni, C., Monarca, B. & Delle Fave, G. (2001) Efficacy of gluten-free diet alone on recovery from iron deficiency anemia in adult celiac patients. American Journal of Gastroenterology, 96, 132–137.
- Aslinia, F., Mazza, J.J. & Yale, S.H. (2006) Megaloblastic anemia and other causes of macrocytosis. Clinical Medicine & Research, 4, 236–241.
- Avni, T., Bieber, A., Grossman, A., Green, H., Leibovici, L. & Gafter-Gvili, A. (2015) The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clinic Proceedings, 90, 12–23.
- Baumgart, D.C. & Sandborn, W.J. (2012) Crohn's disease. Lancet, 380, 1590–1605.
- Bergamaschi, G., Markopoulos, K., Albertini, R., Di Sabatino, A., Biagi, F., Ciccocioppo, R., Arbustini, E. & Corazza, G.R. (2008) Anemia of chronic disease and defective erythropoietin production in patients with celiac disease. Haematologica, 93, 1785–1791.
- Bergamaschi, G., Di Sabatino, A., Albertini, R., Ardizzone, S., Biancheri, P., Bonetti, E., Cassinotti, A., Cazzola, P., Markopoulos, K., Massari, A., Rosti, V., Porro, G.B. & Corazza, G.R. (2010) Prevalence and pathogenesis of anemia in inflammatory bowel disease. Influence of anti-tumor necrosis factor-alpha treatment. Haematologica, 95, 199–205.
- Bergamaschi, G., Di Sabatino, A., Albertini, R., Costanzo, F., Guerci, M., Masotti, M., Pasini, A., Massari, A., Campostrini, N., Corbella, M., Girelli, D. & Corazza, G.R. (2013) Serum hepcidin in inflammatory bowel diseases: biological and clinical significance. Inflammatory Bowel Diseases, 19, 2166–2172.
- Bergamaschi, G., Di Sabatino, A., Pasini, A., Ubezio, C., Costanzo, F., Grataroli, D., Masotti, M., Alvisi, C. & Corazza, G.R. (2017) Intestinal expression of genes implicated in iron absorption and their regulation by hepcidin. Clinical Nutrition, 36, 1427–1433.
- Biagi, F., Marchese, A., Ferretti, F., Ciccocioppo, R., Schiepatti, A., Volta, U., Caio, G., Ciacci, C., Zingone, F., D'Odorico, A., Carroccio, A., Ambrosiano, G., Mansueto, P., Gasbarrini, A., Piscaglia, A.C., Andrealli, A., Astegiano, M., Segato, S., Neri, M., Meggio, A., de Pretis, G., De Vitis, I., Gobbi, P. & Corazza, G.R. (2014) A multicentre case control study on complicated coeliac diasease: two different patterns of natural history, two different prognoses. BMC Gastrenterology, 14, 139.
- Birgegård, G., Henry, D., Glaspy, J., Chopra, R., Thomsen, L.L. & Auerbach, M. (2016) A Randomized Noninferiority trial of intravenous iron isomaltoside versus oral iron sulfate in patients with nonmyeloid malignancies and anemia receiving chemotherapy: the PROFOUND trial. Pharmacotherapy, 36, 402–414.
- Bottaro, G., Cataldo, F., Rotolo, N., Spin, A.M. & Corazza, G.R. (1999) The clinical pattern of subclinical/silent celiac disease: an analysis on 1026 consecutive cases. American Journal of Gastroenterology, 94, 691–696.
- Brugnara, C. (2003) Iron deficiency and erythropoiesis: new diagnostic approaches. Clinical Chemistry, 49, 1573–1578.
- Camaschella, C. (2015) Iron-deficiency anemia. New England Journal of Medicine, 327, 1832–1843.
- Carson, J.L., Guyatt, G., Heddle, N.M., Grossman, B.J., Cohn, C.S., Fung, M.K., Gernsheimer, T., Holcomb, J.B., Kaplan, L.J., Katz, L.M., Peterson, N., Ramsey, G., Rao, S.V., Roback, J.D., Shander, A. & Tobian, A.A. (2016) Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA, 316, 2025–2035.
- Centers for Disease Control and Prevention (1998) Recommendations to prevent and control iron deficiency in the United States. MMWR Recommendations and Reports, 47, 1–29.
- Choi, J.S., Choi, S.J., Lee, K.J., Kim, A., Yoo, J.K., Yang, H.R., Moon, J.S., Chang, J.Y., Ko, J.S. & Kang, G.H. (2015) Clinical manifestations and treatment outcomes of eosinophilic gastroenteritis in children. Pediatric Gastroenterology, Hepatology & Nutrition, 18, 253–260.
- Cianferoni, A. & Spergel, J.M. (2015) Eosinophilic esophagitis and gastroenteritis. Current Allergy and Asthma Reports, 15, 58.
- Cooke, K.S., Hinkle, B., Salimi-Moosavi, H., Foltz, I., King, C., Rathanaswami, P., Winters, A., Steavenson, S., Begley, C.G., Molineux, G. & Sasu, B.J. (2013) A fully human anti-hepcidin antibody modulates iron metabolism in both mice and nonhuman primates. Blood, 122, 3054–3061.
- Corazza, G.R., Valentini, R.A., Andreani, M.L., D'Anchino, M., Leva, M.T., Ginaldi, L., De Feudis, L., Quaglino, D. & Gasbarrini, G. (1995) Subclinical coeliac disease is a frequent cause of iron-deficiency anaemia. Scandinavian Journal of Gastroenterology, 30, 153–156.
- Cotter, T.G. & Pardi, D.S. (2017) Current approach to the evaluation and management of microscopic colitis. Current Gastroenterology Reports, 19, 8–13.
- Dahele, A. & Ghosh, S. (2001) Vitamin B12 deficiency in untreated celiac disease. American Journal of Gastroenterology, 96, 745–750.
- Devalia, V., Hamilton, M.S. & Molloy, A.M.; on behalf of the British Committee for Standards in Haematology. (2014) Guidelines for the diagnosis and treatment of cobalamin and folate disorders. British Journal of Haematology, 166, 496–513.
- Di Sabatino, A. & Corazza, G.R. (2009) Coeliac disease. Lancet, 373, 1480–1493.
- Di Sabatino, A., Biagi, F., Lenzi, M., Frulloni, L., Lenti, M.V., Giuffrida, P. & Corazza, G.R. (2017) Clinical usefulness of serum antibodies as biomarkers of gastrointestinal and liver diseases. Digestive & Liver Disease, 49, 947–956.
- Dickey, W. & Hughes, D.F. (2004) Histology of the terminal ileum in coeliac disease. Scandinavian Journal of Gastroenterology, 39, 665–667.
- Dignass, A.U., Gasche, C., Bettenworth, D., Birgegård, G., Danese, S., Gisbert, J.P., Gomollon, F., Iqbal, T., Katsanos, K., Koutroubakis, I., Magro, F., Savoye, G., Stein, J. & Vavricka, S.; European Crohn's and Colitis Organisation [ECCO]. (2015) European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. Journal of Crohn's and Colitis, 9, 211–222.
- Domènech, E., Mañosa, M., Masnou, H., Navarro, M., Garcia-Planella, E., Bernal, I. & Gassull, M.A. (2005) Infliximab for the treatment of chronic anemia in Crohn's disease. American Journal of Gastroenterology, 100, 496.
- Dufour, C., Brisigotti, M., Fabretti, G., Luxardo, P., Mori, P.G. & Barabino, A. (1993) Helicobacter pylori gastric infection and sideropenic refractory anemia. Journal of Pediatric Gastroenterology and Nutrition, 17, 225–227.
- van Eijk, L.T., John, A.S., Schwoebel, F., Summo, L., Vauléon, S., Zöllner, S., Laarakkers, C.M., Kox, M., van der Hoeven, J.G., Swinkels, D.W., Riecke, K. & Pickkers, P. (2014) Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans. Blood, 124, 2643–2646.
- Evstatiev, R., Marteau, P., Iqbal, T., Khalif, I.L., Stein, J., Bokemeyer, B., Chopey, I.V., Gutzwiller, F.S., Riopel, L. & Gasche, C.; FERGI Study Group. (2011) FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology, 141, 846–853.
- Filmann, N., Rey, J., Schneeweiss, S., Ardizzone, S., Bager, P., Bergamaschi, G., Koutroubakis, I., Lindgren, S., Morena Fde, L., Moum, B., Vavricka, S.R., Schröder, O., Herrmann, E. & Blumenstein, I. (2014) Prevalence of anemia in inflammatory bowel diseases in european countries: a systematic review and individual patient data meta-analysis. Inflammatory Bowel Diseases, 20, 936–945.
- Fine, K.D. (1996) The prevalence of occult gastrointestinal bleeding in celiac sprue. New England Journal of Medicine, 334, 1163–1167.
- Frank, D.N., Robertson, C.E., Hamm, C.M., Kpadeh, Z., Zhang, T., Chen, H., Zhu, W., Sartor, R.B., Boedeker, E.C., Harpaz, N., Pace, N.R. & Li, E. (2011) Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflammatory Bowel Diseases, 17, 179–184.
- Ganzoni, A.M. (1970) Intravenous iron-dextrans: therapeutic and experimental possibilities. Schweizerische Medizinische Wochenschrift, 100, 301–303.
- Gasché, C., Dejaco, C., Waldhoer, T., Tillinger, W., Reinisch, W., Fueger, G.F., Gangl, A. & Lochs, H. (1997) Intravenous iron and erythropoietin for anemia associated with Crohn disease. A randomized, controlled trial. Annals of Internal Medicine, 126, 782–787.
- Gentile, N.M., Murray, J.A. & Pardi, D.S. (2012) Autoimmune enteropathy: a review and update of clinical management. Current gastroenterology Reports, 14, 380–385.
- Girelli, D., Nemeth, E. & Swinkels, D.W. (2016) Hepcidin in the diagnosis of iron disorders. Blood, 127, 2809–2813.
- Goringe, A., Ellis, R., McDowell, I., Vidal-Alaball, J., Jenkins, C., Butler, C. & Worwood, M. (2006) The limited value of methylmalonic acid, homocysteine and holo-transcobalamin in the diagnosis of early B12 deficiency. Haematologica, 91, 231–234.
- Green, R. (2017) Vitamin B12 from the perspective of a practicing hematologist. Blood, 129, 2603–2611.
- Halfdanarson, T.R., Litzow, M.R. & Murray, J.A. (2007) Hematologic manifestations of celiac disease. Blood, 109, 412–421.
- Hamilton, M.S., Blackmore, S. & Lee, A. (2006) Possible cause of false normal B-12 assays. BMJ, 333, 654–655.
- Harper, J.W., Holleran, S.F., Ramakrishnan, R., Bhagat, G. & Green, P.H. (2007) Anemia in celiac disease is multifactorial in etiology. American Journal of Hematology, 82, 996–1000.
- Hershko, C. & Camaschella, C. (2014) How I treat unexplained refractory iron deficiency anemia. Blood, 123, 326–333.
- Hershko, C., Hoffbrand, A.V., Keret, D., Souroujon, M., Maschler, I., Monselise, Y. & Lahad, A. (2005) Role of autoimmune gastritis, Helicobacter pylori and celiac disease in refractory or unexplained iron deficiency anemia. Haematologica, 90, 585–595.
- Hershko, C., Ronson, A., Souroujon, M., Maschler, I., Heyd, J. & Patz, J. (2006) Variable hematologic presentation of autoimmune gastritis: age-related progression from iron deficiency to cobalamin depletion. Blood, 107, 1673–1679.
- Hvas, A.M. & Nexo, E. (2006) Diagnosis and treatment of vitamin B12 deficiency-an update. Haematologica, 91, 1506–1512.
- Jaeggi, T., Kortman, G.A., Moretti, D., Chassard, C., Holding, P., Dostal, A., Boekhorst, J., Timmerman, H.M., Swinkels, D.W., Tjalsma, H., Njenga, J., Mwangi, A., Kvalsvig, J., Lacroix, C. & Zimmermann, M.B. (2015) Iron fortification adversely affects the gut microbiome, increases pathogen abundance and induces intestinal inflammation in Kenyan infants. Gut, 64, 731–742.
- Koutroubakis, I.E., Karmiris, K., Makreas, S., Xidakis, C., Niniraki, M. & Kouroumalis, E.A. (2006) Effectiveness of darbepoetin-alfa in combination with intravenous iron sucrose in patients with inflammatory bowel disease and refractory anaemia: a pilot study. European Journal of Gastroenterology & Hepatology, 18, 421–425.
- Kulnigg, S. & Gasche, C.S. (2006) Systematic review: managing anemia in Crohn's disease. Alimentary Pharmacology & Therapeutics, 24, 1507–1523.
- Lakatos, L., Pandur, T., David, G., Balogh, Z., Kuronya, P., Tollas, A. & Lakatos, P.L. (2003) Association of extraintestinal manifestations of inflammatory bowel disease in a province of western Hungary with disease phenotype: results of a 25-year follow-up study. World Journal of Gastroenterology, 9, 2300–2307.
- Lee, T.W., Kolber, M.R., Fedorak, R.N. & van Zanten, S.V. (2012) Iron replacement therapy in inflammatory bowel disease patients with iron deficiency anemia: a systematic review and meta-analysis. Journal of Crohn's and Colitis, 6, 267–275.
- Leffler, D.A., Green, P.H. & Fasano, A. (2015) Extraintestinal manifestations of coeliac disease. Nature reviews. Gastroenterology & Hepatology, 12, 561–571.
- Leo Carnerero, E., Aoufi, S., Montero Cuadrado, I., Herrera Martin, P. & Herrera Justiniano, J.M. (2009) Autoimmune hemolytic anemia associated with ulcerative colitis: response to infliximab. American Journal of Gastroenterology, 104, 2370–2371.
- Lopez, A., Cacoub, P., Macdougall, I.C. & Peyrin-Biroulet, L. (2016) Iron deficiency anaemia. The Lancet, 387, 907–916.
- Ludvigsson, J.F., Leffler, D.A., Bai, J.C., Biagi, F., Fasano, A., Green, P.H., Hadjivassiliou, M., Kaukinen, K., Kelly, C.P., Leonard, J.N., Lundin, K.E., Murray, J.A., Sanders, D.S., Walker, M.M., Zingone, F. & Ciacci, C. (2013) The Oslo definitions for coeliac disease and related terms. Gut, 62, 43–52.
- Ludvigsson, J.F., Bai, J.C., Biagi, F., Card, T.R., Ciacci, C., Ciclitira, P.J., Green, P.H., Hadjivassiliou, M., Holdoway, A., van Heel, D.A., Kaukinen, K., Leffler, D.A., Leonard, J.N., Lundin, K.E., McGough, N., Davidson, M., Murray, J.A., Swift, G.L., Walker, M.M., Zingone, F. & Sanders, D.S. (2014) Diagnosis and management of adult coeliac disease: guidelines from the British Society of Gastroenterology. Gut, 63, 1210–1228.
- Lundin, K.E. & Alaedini, A. (2012) Non-celiac gluten sensitivity. Gastrointestinal Endoscopy Clinics of North America, 22, 723–734.
- MacDonald, T.T. (2008) The gut is still the biggest lymphoid organ in the body. Mucosal Immunology, 1, 246–247.
- MacDonald, T.T. & Monteleone, G. (2005) Immunity, inflammation, and allergy in the gut. Science, 307, 1920–1925.
- Mafodda, A., Giuffrida, D., Prestifilippo, A., Azzarello, D., Giannicola, R., Mare, M. & Maisano, R. (2017) Oral sucrosomial iron versus intravenous iron in anemic cancer patients without iron deficiency receiving darbepoetin alfa: a pilot study. Supportive Care in Cancer, 25, 2779–2786.
- Mant, M.J., Bain, V.G., Maguire, C.G., Murland, K. & Yacyshyn, B.R. (2006) Prevalence of occult gastrointestinal bleeding in celiac disease. Clinical Gastroenterology and Hepatology, 4, 451–454.
- Martin, J., Geisel, T., Maresch, C., Krieger, K. & Stein, J. (2013) Inadequate nutrient intake in patients with celiac disease: results from a German dietary survey. Digestion, 87, 240–246.
- Mast, A.E., Blinder, M.A., Gronowski, A.M., Chumley, C. & Scott, M.G. (1998) Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations. Clinical Chemistry, 44, 45–51.
- Miceli, E., Lenti, M.V., Padula, D., Luinetti, O., Vattiato, C., Monti, C.M., Di Stefano, M. & Corazza, G.R. (2012) Common features of patients with autoimmune atrophic gastritis. Clinical Gastroenterology and Hepatology, 10, 812–814.
- Mudge, D.W., Tan, K.-S., Miles, R., Johnson, D.W., Badve, S.V., Campbell, S.B., Isbel, N.M., van Eps, C.L. & Hawley, C.M. (2012) A randomized controlled trial of intravenous or oral iron for posttransplant anemia in kidney transplantation. Transplantation, 93, 822–826.
- Negrini, R., Lisato, L., Zanella, I., Cavazzini, L., Gullini, S., Villanacci, V., Poiesi, C., Albertini, A. & Ghielmi, S. (1991) Helicobacter pylori infection induces antibodies cross-reacting with human gastric mucosa. Gastroenterology, 101, 437–445.
- Neumann, W.L., Coss, E., Rugge, M. & Genta, R.M. (2013) Autoimmune atrophic gastritis– pathogenesis, pathology and management. Nature reviews. Gastroenterology & Hepatology, 10, 529–541.
- Okam, M.M., Koch, T.A. & Tran, M.-H. (2017) Iron supplementation, response in iron-deficiency anemia: analysis of five trials. The American Journal of Medicine, 130, 991.e1–991.e8.
- Ordás, I., Eckmann, L., Talamini, M., Baumgart, D.C. & Sandborn, W.J. (2012) Ulcerative colitis. Lancet, 380, 1606–1619.
- Pineton de Chambrun, G., Gonzalez, F., Canva, J.Y., Gonzalez, S., Houssin, L., Desreumaux, P., Cortot, A. & Colombel, J.F. (2011) Natural history of eosinophilic gastroenteritis. Clinical Gastroenterology and Hepatology, 9, 950–956.
- Pisani, A., Riccio, E., Sabbatini, M., Andreucci, M., Del Rio, A. & Visciano, B. (2015) Effect of oral liposomal iron versus intravenous iron for treatment of iron deficiency anaemia in CKD patients: a randomized trial. Nephrology Dialysis Transplantation, 30, 645–652.
- Pizzi, L.T., Weston, C.M., Goldfarb, N.I., Moretti, D., Cobb, N., Howell, J.B., Infantolino, A. & Dimarino, A.J. (2006) Impact of chronic conditions on quality of life in patients with inflammatory bowel disease. Inflamm Bowel Diseases, 12, 47–52.
- Punnonen, K., Irjala, K. & Rajamaki, A. (1997) Serum transferrin receptor ant its ratio to serum ferritin in the diagnosis of iron deficiency. Blood, 89, 1052–1057.
- Qiu, A., Jansen, M., Sakaris, A., Min, S.H., Chattopadhyay, S., Tsai, E., Sandoval, C., Zhao, R., Akabas, M.H. & Goldman, I.D. (2006) Identification of an intestinal folate transporter and the molecular basis for hereditary folate malabsorption. Cell, 127, 917–928.
- Rubio-Tapia, A., Hill, I.D., Kelly, C.P., Calderwood, A.H. & Murray, J.A. (2013) ACG clinical guidelines: diagnosis and management of celiac disease. American Journal of Gastroenterology, 108, 656–676.
- Sassenou, I., Rabhi, M., Berady, S., Hachim, M. & Toloune, F. (2006) Coeliac disease and autoimmunity: about an association with autoimmune haemolytic anaemia. La Revue de Médecine Interne, 27, 75–76.
- Schreiber, S., Howaldt, S., Schnoor, M., Nikolaus, S., Bauditz, J., Gasché, C., Lochs, H. & Raedler, A. (1996) Recombinant erythropoietin for the treatment of anemia in inflammatory bowel disease. New England Journal of Medicine, 334, 619–623.
- Selhub, J., Jacques, P.F., Dallai, G., Choumenkovitch, S. & Rogers, G. (2008) The use of blood concentrations of vitamins and their respective functional indicators to define folate and vitamin B12 status. Food and Nutrition Bulletin, 29, S67–S73.
- Stoffel, N.U., Cercamondi, C.I., Brittenham, G., Zeder, C., Geurts-Moespot, A.J., Swinkels, D.W., Moretti, D. & Zimmermann, M.B. (2017) Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: two open-label, randomised controlled trials. Lancet Haematology, 4, e524–e533.
- Theurl, I., Aigner, E., Theurl, M., Nairz, M., Seifert, M., Schroll, A., Sonnweber, T., Eberwein, L., Witcher, D.R., Murphy, A.T., Wroblewski, V.J., Wurz, E., Datz, C. & Weiss, G. (2009) Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications. Blood, 113, 5277–5286.
- Thompson, T. (2000) Folate, iron, and dietary fiber contents of the gluten-free diet. Journal of the American Dietetic Association, 100, 1389–1396.
- Tien, F.M., Wu, J.F., Jeng, Y.M., Hsu, H.Y., Ni, Y.H., Chang, M.H., Lin, D.T. & Chen, H.L. (2011) Clinical features and treatment responses of children with eosinophilic gastroenteritis. Pediatrics and Neonatology, 52, 272–278.
- Tolkien, Z., Pereira, D.I., Prassmayer, L., Fitt, E., Pot, G., Greenfield, S.M. & Powell, J.J. (2013) Dietary iron does not impact the quality of life of patients with quiescent ulcerative colitis: an observational study. Nutrition Journal, 12, 152.
- U.S. Preventive Services Task Force. (2009) Folic acid for the prevention of neural tube defects: U.S. Preventive Services Task Force recommendation statement. Annals of Internal Medicine, 150, 626–631.
- Uzzan, M., Galicier, L., Gornet, J.M., Oksenhendler, E., Fieschi, C., Allez, M., Bouhnik, Y., Kirchgesner, J., Boutboul, D., Treton, X., Gérard, L., Mahévas, M., Cosnes, J. & Amiot, A. (2017) Autoimmune cytopenias associated with inflammatory bowel diseases: insights from a multicenter retrospective cohort. Digestive and Liver Disease, 249, 397–404.
- Vannella, L., Lahner, E., Osborn, J. & Annibale, B. (2013) Systematic review: gastric cancer incidence in pernicious anemia. Alimentary Pharmacology & Therapeutics, 37, 375–382.
- Volta, U., Bardella, M.T., Calabrò, A., Troncone, R. & Corazza, G.R.; Study Group for Non-Celiac Gluten Sensitivity. (2014) An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC Medicine, 12, 85.
- Wang, C., Graham, D.J., Kane, R.C., Xie, D., Wernecke, M., Levenson, M., MaCurdy, T.E., Houstoun, M., Ryan, Q., Wong, S., Mott, K., Sheu, T.C., Limb, S., Worrall, C., Kelman, J.A. & Reichman, M.E. (2015) Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA, 314, 2062–2068.
- Weiss, G. & Goodnough, L.T. (2005) Anemia of chronic disease. New England Journal of Medicine, 352, 1011–1023.
- Wells, C.W., Lewis, S., Barton, J.R. & Corbett, S. (2006) Effects of changes in hemoglobin level on quality of life and cognitive function in inflammatory bowel disease patients. Inflammatory Bowel Diseases, 12, 123–130.
- WHO. (2011) Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Geneva, Switzerland: World Health Organization.
- WHO. (2012) Serum and red blood cell folate concentrations for assessing folate status in populations. Vitamin and Mineral Nutrition Information System. Geneva, Switzerland: World Health Organization.
- Yuan, L., Geng, L., Ge, L., Yu, P., Duan, X., Chen, J. & Chang, Y. (2013) Effect of iron liposomes on anemia of inflammation. International Journal of Pharmaceutics, 454, 82–89.