Questions and answers on iron deficiency treatment selection and the use of intravenous iron in routine clinical practice

References

• Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372:1832–1843.
   PubMed Web of Science ®Google Scholar
• Cheong Y, Cameron IT, Critchley HOD. Abnormal uterine bleeding. Br Med Bull. 2019;131:119.
   PubMed Web of Science ®Google Scholar
• Forbes A, Escher J, Hébuterne X, et al. ESPEN guideline: clinical nutrition in inflammatory bowel disease. Clin Nutr. 2017;36:321–347.
   PubMed Web of Science ®Google Scholar
• Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Int (Suppl). 2012;2:279–335.
   Web of Science ®Google Scholar
• Ponikowski P, Voors AA, Anker SD, Bueno H, et al., ESC Scientific Document Group. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37:2129–2200.
   PubMed Web of Science ®Google Scholar
• Cappellini MD, Musallam KM, Taher AT. Iron deficiency anaemia revisited. J Intern Med. 2020;287:153–170.
   PubMed Web of Science ®Google Scholar
• Auerbach M, Gafter-Gvili A, Macdougall IC. Intravenous iron: a framework for changing the management of iron deficiency. Lancet Haematol. 2020;7:e342–e50.
   PubMed Web of Science ®Google Scholar
• Muckenthaler MU, Rivella S, Hentze MW, et al. A red carpet for iron metabolism. Cell. 2017;168:344–361.
   PubMed Web of Science ®Google Scholar
• Oexle H, Gnaiger E, Weiss G. Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation. Biochim Biophys Acta. 1999;1413:99–107.
   PubMed Web of Science ®Google Scholar
• Beard JL. Iron biology in immune function, muscle metabolism and neuronal functioning. J Nutr. 2001;131:568S–579S. discussion 80S.
   PubMed Web of Science ®Google Scholar
• Camaschella C. Iron deficiency. Blood. 2019;133:30–39.
   PubMed Web of Science ®Google Scholar
• Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood. 2019;133:40–50.
   PubMed Web of Science ®Google Scholar
• Goddard AF, James MW, McIntyre AS, et al., British Society of Gastroenterology. Guidelines for the management of iron deficiency anaemia. Gut. 2011;60:1309–1316.
   PubMed Web of Science ®Google Scholar
• Ganz T, Nemeth E. Iron balance and the role of hepcidin in chronic kidney disease. Semin Nephrol. 2016;36:87–93.
   PubMed Web of Science ®Google Scholar
• Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010;116:4754–4761.
   PubMed Web of Science ®Google Scholar
• Weiss G. Anemia of chronic disorders: new diagnostic tools and new treatment strategies. Semin Hematol. 2015;52:313–320.
   PubMed Web of Science ®Google Scholar
• Girelli D, Nemeth E, Swinkels DW. Hepcidin in the diagnosis of iron disorders. Blood. 2016;127:2809–2813.
   PubMed Web of Science ®Google Scholar
• Cook JD, Reddy MB. Efficacy of weekly compared with daily iron supplementation. Am J Clin Nutr. 1995;62:117–120.
   PubMed Web of Science ®Google Scholar
• Bhandari S, Pereira DIA, Chappell HF, et al. Intravenous irons: from basic science to clinical practice. Pharmaceuticals (Basel. ). 2018;11:82.
   PubMedGoogle Scholar
• Sangkhae V, Nemeth E. Regulation of the iron homeostatic hormone hepcidin. Adv Nutr. 2017;8:126–136.
   PubMed Web of Science ®Google Scholar
• Camaschella C, Pagani A. Advances in understanding iron metabolism and its crosstalk with erythropoiesis. Br J Haematol. 2018;182:481–494.
   PubMed Web of Science ®Google Scholar
• Dibb M, Subramanian S. Anaemia in inflammatory bowel disease. Frontline Gastroenterol. 2014;5:190–196.
   PubMedGoogle Scholar
• Dignass AU, Gasche C, Bettenworth D, European Crohn’s and Colitis Organisation [ECCO], 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.
   PubMed Web of Science ®Google Scholar
• Stoffel NU, Zeder C, Brittenham GM, et al. Iron absorption from supplements is greater with alternate day than with consecutive day dosing in iron-deficient anemic women. Haematologica. 2020;105:1232–1239.
   PubMed Web of Science ®Google Scholar
• Macdougall IC, Bock AH, Carrera F, on behalf of the FIND-CKD Study Investigators, et al. FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transplant. 2014;29:2075–2084.
   PubMed Web of Science ®Google Scholar
• Richardson D, Bartlett C, Jolly H, et al. Intravenous iron for CAPD populations: proactive or reactive strategies? Nephrol Dial Transplant. 2001;16:115–119.
   PubMed Web of Science ®Google Scholar
• Roger SD, Tio M, Park HC, et al. Intravenous iron and erythropoiesis-stimulating agents in haemodialysis: a systematic review and meta-analysis. Nephrology (Carlton). 2017;22:969–976.
   PubMed Web of Science ®Google Scholar
• Macdougall IC, White C, Anker SD, et al. Intravenous iron in patients undergoing maintenance hemodialysis. N Engl J Med. 2019;380:447–458.
   PubMed Web of Science ®Google Scholar
• Ganz T, Aronoff GR, Gaillard CAJM, et al. Iron administration, infection, and anemia management in CKD: Untangling the effects of intravenous iron therapy on immunity and infection risk. Kidney Med. 2020;2:341–353.
   PubMedGoogle Scholar
• Wish JB, Aronoff GR, Bacon BR, et al. Positive iron balance in chronic kidney disease: How much is too much and how to tell? Am J Nephrol. 2018;47:72–83.
   PubMed Web of Science ®Google Scholar
• Jankowska EA, Rozentryt P, Witkowska A, et al. Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J. 2010;31:1872–1880.
   PubMed Web of Science ®Google Scholar
• Rocha BML, Cunha GJL, Menezes Falcão LF. The burden of iron deficiency in Heart Failure: Therapeutic Approach. J Am Coll Cardiol. 2018;71:782–793.
   PubMed Web of Science ®Google Scholar
• Anker SD, Comin Colet J, Filippatos G, et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med. 2009;361:2436–2448.
   PubMed Web of Science ®Google Scholar
• Anker SD, Kirwan BA, van Veldhuisen DJ, et al. Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis. Eur J Heart Fail. 2018;20:125–133.
   PubMed Web of Science ®Google Scholar
• Jankowska EA, Tkaczyszyn M, Suchocki T, et al. Effects of intravenous iron therapy in iron-deficient patients with systolic heart failure: a meta-analysis of randomized controlled trials. Eur J Heart Fail. 2016;18:786–795.
   PubMed Web of Science ®Google Scholar
• Kapoor M, Schleinitz MD, Gemignani A, et al. Outcomes of patients with chronic heart failure and iron deficiency treated with intravenous iron: a meta-analysis. Cardiovasc Hematol Disord Drug Targets. 2013;13:35–44.
   PubMedGoogle Scholar
• Ponikowski P, van Veldhuisen DJ, Comin-Colet J, for the CONFIRM-HF Investigators, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J. 2015;36:657–668.
   PubMed Web of Science ®Google Scholar
• Filippatos G, Farmakis D, Colet JC, et al. Intravenous ferric carboxymaltose in iron-deficient chronic heart failure patients with and without anaemia: a subanalysis of the FAIR-HF trial. Eur J Heart Fail. 2013;15:1267–1276.
   PubMed Web of Science ®Google Scholar
• Ponikowski P, Kirwan BA, Anker SD, et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicentre, double-blind, randomised, controlled trial. Lancet. 2020;396:1895–1904.
   PubMed Web of Science ®Google Scholar
• Lewis GD, Malhotra R, Hernandez AF, et al., for the NHLBI Heart Failure Clinical Research Network. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: The IRONOUT HF randomized clinical trial. JAMA. 2017;317:1958–1966.
   PubMed Web of Science ®Google Scholar
• Kotecha D, Ngo K, Walters JA, et al. Erythropoietin as a treatment of anemia in heart failure: systematic review of randomized trials. Am Heart J. 2011;161:822–831.e2.
   PubMed Web of Science ®Google Scholar
• Swedberg K, Young JB, Anand IS, et al., RED-HF Investigators. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013;368:1210–1219.
   PubMed Web of Science ®Google Scholar
• World Health Organisation. Iron deficiency anaemia: assessment, prevention, and control; 2001. WHO/NHD/01.3.
   Google Scholar
• Crispin P, Stephens B, McArthur E, et al. First trimester ferritin screening for pre-delivery anaemia as a patient blood management strategy. Transfus Apher Sci. 2019;58:50–57.
   PubMed Web of Science ®Google Scholar
• Daru J, Zamora J, Fernandez-Felix BM, et al. Risk of maternal mortality in women with severe anaemia during pregnancy and post partum: a multilevel analysis. Lancet Glob Health. 2018;6:e548–e554.
   PubMed Web of Science ®Google Scholar
• Bergmann RL, Richter R, Bergmann KE, et al. Prevalence and risk factors for early postpartum anemia. Eur J Obstet Gynecol Reprod Biol. 2010;150:126–131.
   PubMed Web of Science ®Google Scholar
• Breymann C, Honegger C, Hosli I, et al. Diagnosis and treatment of iron-deficiency anaemia in pregnancy and postpartum. Arch Gynecol Obstet. 2017;296:1229–1234.
   PubMed Web of Science ®Google Scholar
• Lewkowitz AK, Gupta A, Simon L, et al. Intravenous compared with oral iron for the treatment of iron-deficiency anemia in pregnancy: a systematic review and meta-analysis. J Perinatol. 2019;39:519–532.
   PubMed Web of Science ®Google Scholar
• Sultan P, Bampoe S, Shah R, et al. Oral vs intravenous iron therapy for postpartum anemia: a systematic review and meta-analysis. Am J Obstet Gynecol. 2019;221:19–29.e3.
   PubMed Web of Science ®Google Scholar
• Holm C, Thomsen LL, Norgaard A, et al. Single-dose intravenous iron infusion or oral iron for treatment of fatigue after postpartum haemorrhage: a randomized controlled trial. Vox Sang. 2017;112:219–228.
   PubMed Web of Science ®Google Scholar
• NICE, editor. Heavy menstrual bleeding. London (UK): National Institute for Health and Clinical Excellence; 2007.
   Google Scholar
• National Institute for Health and Care Excellence. Heavy menstrual bleeding: assessment and management. NICE guideline (NG88). London; 2018 March 14, 2018.
   Google Scholar
• Hallberg L, Hogdahl AM, Nilsson L, et al. Menstrual blood loss-a population study. Variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand. 1966;45:320–351.
   PubMed Web of Science ®Google Scholar
• Fraser IS, McCarron G, Markham R. A preliminary study of factors influencing perception of menstrual blood loss volume. Am J Obstet Gynecol. 1984;149:788–793.
   PubMed Web of Science ®Google Scholar
• Liu Z, Doan QV, Blumenthal P, et al. A systematic review evaluating health-related quality of life, work impairment, and health-care costs and utilization in abnormal uterine bleeding. Value Health. 2007;10:183–194.
   PubMed Web of Science ®Google Scholar
• Schoep ME, Nieboer TE, van der Zanden M, et al. The impact of menstrual symptoms on everyday life: a survey among 42,879 women. Am J Obstet Gynecol. 2019;220:569 e1–e7.
   PubMed Web of Science ®Google Scholar
• Fraser IS, Mansour D, Breymann C, et al. Prevalence of heavy menstrual bleeding and experiences of affected women in a European patient survey. Int J Gynaecol Obstet. 2015;128:196–200.
   PubMed Web of Science ®Google Scholar
• Henry C, Ekeroma A, Filoche S. Barriers to seeking consultation for abnormal uterine bleeding: systematic review of qualitative research. BMC Womens Health. 2020;20:123.
   PubMed Web of Science ®Google Scholar
• Munro MG, Critchley HO, Broder MS, et al., FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113:3–13.
   PubMed Web of Science ®Google Scholar
• Munro MG, Critchley HOD, Fraser IS, Committee FMD. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynaecol Obstet. 2018;143:393–408.
   PubMed Web of Science ®Google Scholar
• Cancelo-Hidalgo MJ, Castelo-Branco C, Palacios S, et al. Tolerability of different oral iron supplements: a systematic review. Curr Med Res Opin. 2013;29:291–303.
   PubMed Web of Science ®Google Scholar
• Shand AW, Bell J, Henry A, et al. Rapid increase in intravenous iron therapy for women of reproductive age in Australia. Med J Aust. 2020;213:85–86.
   PubMed Web of Science ®Google Scholar
• Chertow GM, Mason PD, Vaage-Nilsen O, et al. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant. 2006;21:378–382.
   PubMed Web of Science ®Google Scholar
• Wang C, Graham DJ, Kane RC, et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA. 2015;314:2062–2068.
   PubMed Web of Science ®Google Scholar
• Patton K, Borshoff DC. Adverse drug reactions. Anaesthesia. 2018;73:76–84.
   PubMed Web of Science ®Google Scholar
• Avni T, Bieber A, Grossman A, et al. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc. 2015;90:12–23.
   PubMed Web of Science ®Google Scholar
• Morales Mateluna CA, Scherer Hofmeier K, Bircher AJ. Approach to hypersensitivity reactions from intravenous iron preparations. Allergy. 2017;72:827–830.
   PubMed Web of Science ®Google Scholar
• Canning M, Grannell L. A stain on iron therapy. Aust Prescr. 2020;43:160–163.
   PubMed Web of Science ®Google Scholar
• Eggenschwiler CDC, Dummer R, Imhof L. Use of lasers for iron-induced accidental tattoos: experience at a tertiary referral center. Dermatol Surg. 2020;46:1176–1182.
   PubMed Web of Science ®Google Scholar
• Fishbane S, Ungureanu VD, Maesaka JK, et al. The safety of intravenous iron dextran in hemodialysis patients. Am J Kidney Dis. 1996;28:529–534.
   PubMed Web of Science ®Google Scholar
• Szebeni J, Fishbane S, Hedenus M, et al. Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management. Br J Pharmacol. 2015;172:5025–5036.
   PubMed Web of Science ®Google Scholar
• Auerbach M, Adamson J, Bircher A, et al. On the safety of intravenous iron, evidence trumps conjecture. Haematologica. 2015;100:e214–e215.
   PubMed Web of Science ®Google Scholar
• Barton JC, Barton EH, Bertoli LF, et al. Intravenous iron dextran therapy in patients with iron deficiency and normal renal function who failed to respond to or did not tolerate oral iron supplementation. Am J Med. 2000;109:27–32.
   PubMed Web of Science ®Google Scholar
• DeLoughery TG. Safety of Oral and Intravenous Iron. Acta Haematol. 2019;142:8–12.
   PubMed Web of Science ®Google Scholar
• Gómez-Ramírez S, Shander A, Spahn DR, et al. Prevention and management of acute reactions to intravenous iron in surgical patients. Blood Transfus. 2019;17:137–145.
   PubMed Web of Science ®Google Scholar
• Lim W, Afif W, Knowles S, et al. Canadian expert consensus: management of hypersensitivity reactions to intravenous iron in adults. Vox Sang. 2019;114:363–373.
   PubMed Web of Science ®Google Scholar
• Rampton D, Folkersen J, Fishbane S, et al. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica. 2014;99:1671–1676.
   PubMed Web of Science ®Google Scholar
• Auerbach M, Ballard H, Glaspy J. Clinical update: intravenous iron for anaemia. Lancet. 2007;369:1502–1504.
   PubMed Web of Science ®Google Scholar
• Bircher AJ, Auerbach M. Hypersensitivity from intravenous iron products. Immunol Allergy Clin North Am. 2014;34:707–23. x–xi.
   PubMed Web of Science ®Google Scholar
• Drexler C, Macher S, Lindenau I, et al. High-dose intravenous versus oral iron in blood donors with iron deficiency: the IronWoMan randomized, controlled clinical trial. Clin Nutr. 2020;39:737–745.
   PubMed Web of Science ®Google Scholar
• Wolf M, Koch TA, Bregman DB. Effects of iron deficiency anemia and its treatment on fibroblast growth factor 23 and phosphate homeostasis in women. J Bone Miner Res. 2013;28:1793–1803.
   PubMed Web of Science ®Google Scholar
• Rosano G, Schiefke I, Göhring UM, et al. A pooled analysis of serum phosphate measurements and potential hypophosphataemia events in 45 interventional trials with ferric carboxymaltose. J Clin Med. 2020;9:3587.
   PubMed Web of Science ®Google Scholar
• Zoller H, Schaefer B, Glodny B. Iron-induced hypophosphatemia: an emerging complication. Curr Opin Nephrol Hypertens. 2017;26:266–275.
   PubMed Web of Science ®Google Scholar
• Vifor Pharma UK Ltd. Ferinject (ferric carboxymaltose) summary of product characteristics. 2020 Oct. Available from: https://www.medicines.org.uk/emc/product/5910/smpc
   Google Scholar
• Glaspy JA, Lim-Watson MZ, Libre MA, et al. Hypophosphatemia associated with intravenous iron therapies for iron deficiency anemia: a systematic literature review. Ther Clin Risk Manag. 2020;16:245–259.
   PubMed Web of Science ®Google Scholar
• Wolf M, Rubin J, Achebe M, et al. Effects of iron isomaltoside vs ferric carboxymaltose on hypophosphatemia in iron-deficiency anemia: two randomized clinical trials. JAMA. 2020;323:432–443.
   PubMed Web of Science ®Google Scholar
• Lamb CA, Kennedy NA, Raine T, IBD guidelines eDelphi consensus group, et al. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019;68:s1–s106.
   PubMed Web of Science ®Google Scholar
• Huang LL, Lee D, Troster SM, Kent AB, et al. A controlled study of the effects of ferric carboxymaltose on bone and haematinic biomarkers in chronic kidney disease and pregnancy. Nephrol Dial Transplant. 2018;33:1628–1635.
   PubMed Web of Science ®Google Scholar
• Stöhr R, Sandstede L, Heine GH, et al. High-dose ferric carboxymaltose in patients with HFrEF induces significant hypophosphatemia. J Am Coll Cardiol. 2018;71:2270–2271.
   PubMed Web of Science ®Google Scholar