Iron is an abundant element that is essential for multiple biologic processes. Iron metabolism is not entirely understood, but since the discovery of hepcidin, much progress has been made especially in the last five years. This article is intended to enhance clinician understanding of iron metabolism which may inform decisions about parenteral iron use in iron-restricted erythropoiesis (IResE). This article briefly discusses intravenous (IV) iron utilization in iron deficiency, anemia of chronic inflammation (ACI), functional iron deficiency (FID), and anemia associated with chronic kidney disease, heart failure, pregnancy, inflammatory bowel disease and cancer. Oral iron therapy is valuable in mild to moderate pure iron deficiency. Intravenous iron is required when a prompt response is needed in severe pure iron deficiency. ACI is a hypoferremic state resulting from altered iron metabolism. In ACI, IV iron is needed to overcome the blocking effects of hepcidin on intestinal absorption. ESAs stimulate erythropoiesis increasing iron utilization. This surge in iron requirement can result in FID, especially when ESAs are used in patients with ACI. Intravenous iron is required to treat or avoid iron deficiency in FID when inflammation is present. Parenteral iron maximizes ESA response and can make using erythropoiesis-stimulating agents (ESAs) safer by being ESA sparing. The complex and seemingly ubiquitous nature of iron in humans and the inadequate methods of assessment of iron status in inflammatory states means clinical and laboratory monitoring and individualization of care remain essential. The decision to administer intravenous iron is complex as it often lacks robust consensus guidelines; despite this we can expect utilization of these products to increase as they are safe, effective and necessary.
| Published in | American Journal of Internal Medicine (Volume 8, Issue 6) |
| DOI | 10.11648/j.ajim.20200806.19 |
| Page(s) | 289-303 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Iron, Parenteral Iron, Intravenous Iron, Hepcidin, Ferroportin, Anemia, Metabolism
| [1] | Evstatiev R, Gasche C. Iron sensing and signaling. Gut. 2012; 61 (6): 933-952. DOI: 10.1136/gut.2010.214312. |
| [2] | Institute of Medicine 2006. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press. P. 328-339. |
| [3] | Dev S, Babitt JL. Overview of iron metabolism in health and disease. Hemodial Int. 2017; 21 Suppl 1 (Suppl 1): S6-S20. DOI: 10.1111/hdi.12542. |
| [4] | Ganz T. Systemic iron homeostasis. Physiol Rev. 2013; 93 (4): 1721-1741. DOI: 10.1152/physrev.00008.2013. |
| [5] | Gammella E, Buratti P, Cairo G, Recalcati S. Macrophages: central regulators of iron balance. Metallomics. 2014; 6 (8): 1336-1345. DOI: 10.1039/c4mt00104d. |
| [6] | Muckenthaler MU, Rivella S, Hentze MW, Galy B. A Red Carpet for Iron Metabolism. Cell. 2017; 168 (3): 344-361. DOI: 10.1016/j.cell.2016.12.034. |
| [7] | Hennigar SR, McClung JP. Nutritional Immunity: Starving Pathogens of Trace Minerals. Am J Lifestyle Med. 2016; 10 (3): 170-173. Published 2016 Feb 4. DOI: 10.1177/1559827616629117. |
| [8] | Nairz M, Dichtl S, Schroll A, et al. Iron and innate antimicrobial immunity-Depriving the pathogen, defending the host. J Trace Elem Med Biol. 2018; 48: 118-133. DOI: 10.1016/j.jtemb.2018.03.007. |
| [9] | Camaschella C. Iron deficiency. Blood. 2019; 133 (1): 30-39. DOI: 10.1182/blood-2018-05-815944. |
| [10] | Kassebaum NJ, Jasrasaria R, Naghavi M, et al. A systematic analysis of global anemia burden from 1990 to 2010. Blood. 2014; 123 (5): 615-624. DOI: 10.1182/blood-2013-06-508325. |
| [11] | Feb 28, 2020 - Get the latest research information from NIH: https: //www.nih.gov/... Iron. Fact Sheet for Health Professionals. A woman discussing supplements with a pharmacist. Have a question? Ask ODS Join the ODS Email List. |
| [12] | Moretti D, Goede JS, Zeder C, et al. Oral iron supplements increase hepcidin and decrease iron absorption from daily or twice-daily doses in iron-depleted young women. Blood. 2015; 126 (17): 1981-1989. DOI: 10.1182/blood-2015-05-642223 |
| [13] | Stoffel NU, Cercamondi CI, Brittenham G, et al. 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 Haematol. 2017; 4 (11): e524-e533. DOI: 10.1016/S2352-3026(17)30182-5. |
| [14] | Wood JC. Guidelines for quantifying iron overload. Hematology Am Soc Hematol Educ Program. 2014 (1): 210-215. DOI: 10.1182/ashedu. |
| [15] | Weiss G, Ganz T, Goodnough LT. Anemia of inflammation. Blood. 2019; 133 (1): 40-50. DOI: 10.1182/blood-2018-06-856500cation-2014.1.210. |
| [16] | Ganz, T. Anemia of Inflammation. N. Engl. J. Med. 2019, 381, 1148–1157. |
| [17] | Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010; 116 (23): 4754-4761. DOI: 10.1182/blood-2010-05-286260. |
| [18] | Truman-Rosentsvit M, Berenbaum D, Spektor L, et al. Ferritin is secreted via 2 distinct nonclassical vesicular pathways. Blood. 2018; 131 (3): 342-352. DOI: 10.1182/blood-2017-02-768580. |
| [19] | Camaschella C. Iron deficiency: new insights into diagnosis and treatment. Hematology Am Soc Hematol Educ Program. 2015; 2015: 8-13. DOI: 10.1182/asheducation-2015.1.8. |
| [20] | Leers MP, Keuren JF, Oosterhuis WP. The value of the Thomas-plot in the diagnostic work up of anemic patients referred by general practitioners. Int J Lab Hematol. 2010; 32 (6 Pt 2): 572-581. DOI: 10.1111/j.1751-553X.2010.01221.x. |
| [21] | Enko D, Wallner F, von-Goedecke A, Hirschmugl C, Auersperg V, Halwachs-Baumann G. The impact of an algorithm-guided management of preoperative anemia in perioperative hemoglobin level and transfusion of major orthopedic surgery patients. Anemia. 2013; 2013: 641876. DOI: 10.1155/2013/641876. |
| [22] | Okonko DO, Marley SB, Anker SD, Poole-Wilson PA, Gordon MY. Erythropoietin resistance contributes to anaemia in chronic heart failure and relates to aberrant JAK-STAT signal transduction. Int J Cardiol. 2013; 164 (3): 359-364. DOI: 10.1016/j.ijcard.2011.07.045. |
| [23] | Michels KR, Zhang Z, Bettina AM, et al. Hepcidin-mediated iron sequestration protects against bacterial dissemination during pneumonia. JCI Insight. 2017; 2 (6): e92002. Published 2017 Mar 23. DOI: 10.1172/jci.insight.92002. |
| [24] | Stefanova D, Raychev A, Deville J, et al. Hepcidin Protects against Lethal Escherichia coli Sepsis in Mice Inoculated with Isolates from Septic Patients. Infect Immun. 2018; 86 (7): e00253-18. Published 2018 Jun 21. DOI: 10.1128/IAI.00253-18. |
| [25] | Park CH, Valore EV, Waring AJ, Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem. 2001; 276 (11): 7806-7810. DOI: 10.1074/jbc.M008922200. |
| [26] | Song SN, Tomosugi N, Kawabata H, Ishikawa T, Nishikawa T, Yoshizaki K. Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease. Blood. 2010; 116 (18): 3627-3634. DOI: 10.1182/blood-2010-03-271791. |
| [27] | Song SN, Iwahashi M, Tomosugi N, et al. Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients. Arthritis Res Ther. 2013; 15 (5): R141. Published 2013 Oct 2. DOI: 10.1186/ar4323. |
| [28] | Fishbane S, Ross DW, Hong S. Anemia in Non-Dialysis-Dependent CKD: To Treat or Not to Treat?. Am J Kidney Dis. 2019; 73 (3): 297-299. DOI: 10.1053/j.ajkd.2018.11.006. |
| [29] | Tobu M, Iqbal O, Fareed D, et al. Erythropoietin-induced thrombosis as a result of increased inflammation and thrombin activatable fibrinolytic inhibitor. Clin Appl Thromb Hemost. 2004; 10 (3): 225-232. DOI: 10.1177/107602960401000304. |
| [30] | Glaspy JA. Erythropoietin in cancer patients. Annu Rev Med. 2009; 60: 181-192. DOI: 10.1146/annurev.med.60.050307.110718. |
| [31] | Chen TK, Estrella MM, Astor BC, et al. Longitudinal changes in hematocrit in hypertensive chronic kidney disease: results from the African-American Study of Kidney Disease and Hypertension (AASK). Nephrol Dial Transplant. 2015; 30 (8): 1329-1335. DOI: 10.1093/ndt/gfv037. |
| [32] | Chonchol M, Lippi G, Montagnana M, Muggeo M, Targher G. Association of inflammation with anaemia in patients with chronic kidney disease not requiring chronic dialysis. Nephrol Dial Transplant. 2008; 23 (9): 2879-2883. DOI: 10.1093/ndt/gfn109. |
| [33] | Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (1988-1994). Arch Intern Med. 2002; 162 (12): 1401-1408. DOI: 10.1001/archinte.162.12.1401. |
| [34] | Bachmann S, Le Hir M, Eckardt KU. Co-localization of erythropoietin mRNA and ecto-5'-nucleotidase immunoreactivity in peritubular cells of rat renal cortex indicates that fibroblasts produce erythropoietin. J Histochem Cytochem. 1993; 41 (3): 335-341. DOI: 10.1177/41.3.8429197. |
| [35] | Maxwell PH, Osmond MK, Pugh CW, et al. Identification of the renal erythropoietin-producing cells using transgenic mice. Kidney Int. 1993; 44 (5): 1149-1162. DOI: 10.1038/ki.1993.362. |
| [36] | Macdougall IC. Intravenous iron therapy in patients with chronic kidney disease: recent evidence and future directions. Clin Kidney J. 2017; 10 (Suppl 1): i16-i24. DOI: 10.1093/ckj/sfx043. |
| [37] | Tonia T, Mettler A, Robert N, et al. Erythropoietin or darbepoetin for patients with cancer. Cochrane Database Syst Rev. 2012; 12: CD003407. Published 2012 Dec 12. DOI: 10.1002/14651858.CD003407.pub5. |
| [38] | Thavarajah S, Choi MJ. The Use of Erythropoiesis-Stimulating Agents in Patients With CKD and Cancer: A Clinical Approach. Am J Kidney Dis. 2019; 74 (5): 667-674. DOI: 10.1053/j.ajkd.2019.04.022. |
| [39] | Begum S, Latunde-Dada GO. Anemia of Inflammation with An Emphasis on Chronic Kidney Disease. Nutrients. 2019; 11 (10): 2424. Published 2019 Oct 11. DOI: 10.3390/nu11102424. |
| [40] | Macdougall IC, White C, Anker SD, et al. Intravenous Iron in Patients Undergoing Maintenance Hemodialysis [published correction appears in N Engl J Med. 2019 Jan 14;:]. N Engl J Med. 2019; 380 (5): 447-458. DOI: 10.1056/NEJMoa1810742. |
| [41] | Singh AK, Szczech L, Tang KL, et al. Correction of anemia with epoetin alfa in chronic kidney disease. N Engl J Med. 2006; 355 (20): 2085-2098. DOI: 10.1056/NEJMoa065485. |
| [42] | Li H, Wang SX. Intravenous iron sucrose in peritoneal dialysis patients with renal anemia. Perit Dial Int. 2008; 28 (2): 149-154. |
| [43] | Singh H, Reed J, Noble S, Cangiano JL, Van Wyck DB; United States Iron Sucrose (Venofer) Clinical Trials Group. Effect of intravenous iron sucrose in peritoneal dialysis patients who receive erythropoiesis-stimulating agents for anemia: a randomized, controlled trial. Clin J Am Soc Nephrol. 2006; 1 (3): 475-482. DOI: 10.2215/CJN.01541005. |
| [44] | Ali MA, Luxton AW, Walker WH. Serum ferritin concentration and bone marrow iron stores: a prospective study. Can Med Assoc J. 1978; 118 (8): 945-946. |
| [45] | Ali M, Rigolosi R, Fayemi AO, Braun EV, Frascino J, Singer R. Failure of serum ferritin levels to predict bone-marrow iron content after intravenous iron-dextran therapy. Lancet. 1982; 1 (8273): 652-655. DOI: 10.1016/s0140-6736(82)92204-8. |
| [46] | Del Vecchio L, Longhi S, Locatelli F. Safety concerns about intravenous iron therapy in patients with chronic kidney disease. Clin Kidney J. 2016; 9 (2): 260-267. DOI: 10.1093/ckj/sfv142. |
| [47] | Bárány P, Eriksson LC, Hultcrantz R, Pettersson E, Bergström J. Serum ferritin and tissue iron in anemic dialysis patients. Miner Electrolyte Metab. 1997; 23 (3-6): 273-276. |
| [48] | Dixon SJ, Stockwell BR. The role of iron and reactive oxygen species in cell death. Nat Chem Biol. 2014; 10 (1): 9-17. DOI: 10.1038/nchembio.1416. |
| [49] | Agarwal R, Kusek JW, Pappas MK. A randomized trial of intravenous and oral iron in chronic kidney disease. Kidney Int. 2015; 88 (4): 905-914. DOI: 10.1038/ki.2015.163. |
| [50] | Macdougall IC, Bock AH, Carrera F, 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 (11): 2075-2084. DOI: 10.1093/ndt/gfu201. |
| [51] | Bhandari S, Kalra PA, Coyne DW. Data confusion. Kidney Int. 2015; 88 (6): 1445. DOI: 10.1038/ki.2015.303. |
| [52] | Macdougall IC, Roger SD. New data on the safety of IV iron-but why the discrepancy with FIND-CKD?. Kidney Int. 2015; 88 (6): 1445-1446. DOI: 10.1038/ki.2015.302. |
| [53] | Agarwal R. The Author Replies. Kidney Int. 2015; 88 (6): 1446-1447. DOI: 10.1038/ki.2015.304. |
| [54] | Mehta JL, Pothineni NV. Inflammation in Heart Failure: The Holy Grail?. Hypertension. 2016; 68 (1): 27-29. DOI: 10.1161/HYPERTENSIONAHA.116.07307. |
| [55] | Shirazi LF, Bissett J, Romeo F, Mehta JL. Role of Inflammation in Heart Failure. Curr Atheroscler Rep. 2017; 19 (6): 27. DOI: 10.1007/s11883-017-0660-356. |
| [56] | Okonko DO, Mandal AK, Missouris CG, Poole-Wilson PA. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J Am Coll Cardiol. 2011; 58 (12): 1241-1251. DOI: 10.1016/j.jacc.2011.04.040. |
| [57] | Kasner M, Aleksandrov AS, Westermann D, et al. Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. Int J Cardiol. 2013; 168 (5): 4652-4657. DOI: 10.1016/j.ijcard.2013.07.185. |
| [58] | Anand IS, Gupta P. Anemia and Iron Deficiency in Heart Failure: Current Concepts and Emerging Therapies. Circulation. 2018; 138 (1): 80-98. DOI: 10.1161/CIRCULATIONAHA.118.030099. |
| [59] | Anand IS, Kuskowski MA, Rector TS, et al. Anemia and change in hemoglobin over time related to mortality and morbidity in patients with chronic heart failure: results from Val-HeFT. Circulation. 2005; 112 (8): 1121-1127. DOI: 10.1161/CIRCULATIONAHA.104.512988. |
| [60] | Montero D, Lundby C, Ruschitzka F, Flammer AJ. True Anemia-Red Blood Cell Volume Deficit-in Heart Failure: A Systematic Review. Circ Heart Fail. 2017; 10 (5): e003610. DOI: 10.1161/CIRCHEARTFAILURE.116.003610. |
| [61] | McMahon LP, Mason K, Skinner SL, Burge CM, Grigg LE, Becker GJ. Effects of haemoglobin normalization on quality of life and cardiovascular parameters in end-stage renal failure. Nephrol Dial Transplant. 2000; 15 (9): 1425-1430. DOI: 10.1093/ndt/15.9.1425. |
| [62] | Ezekowitz JA, McAlister FA, Armstrong PW. Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation. 2003; 107 (2): 223-225. DOI: 10.1161/01.cir.0000052622.51963.fc. |
| [63] | 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 (7): 786-795. DOI: 10.1002/ejhf.473. |
| [64] | Jankowska EA, von Haehling S, Anker SD, Macdougall IC, Ponikowski P. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J. 2013; 34 (11): 816-829. DOI: 10.1093/eurheartj/ehs224. |
| [65] | Lakhal-Littleton S, Wolna M, Chung YJ, et al. An essential cell-autonomous role for hepcidin in cardiac iron homeostasis. Elife. 2016; 5: e19804. Published 2016 Nov 29. DOI: 10.7554/eLife.19804. |
| [66] | Núñez J, Domínguez E, Ramón JM, et al. Iron deficiency and functional capacity in patients with advanced heart failure with preserved ejection fraction. Int J Cardiol. 2016; 207: 365-367. DOI: 10.1016/j.ijcard.2016.01.187. |
| [67] | Lewis GD, Semigran MJ, Givertz MM, et al. Oral Iron Therapy for Heart Failure With Reduced Ejection Fraction: Design and Rationale for Oral Iron Repletion Effects on Oxygen Uptake in Heart Failure. Circ Heart Fail. 2016; 9 (5): e000345. DOI: 10.1161/CIRCHEARTFAILURE.115.000345. |
| [68] | 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 (25): 2436-2448. DOI: 10.1056/NEJMoa0908355. |
| [69] | Ponikowski P, van Veldhuisen DJ, Comin-Colet J, 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 (11): 657-668. DOI: 10.1093/eurheartj/ehu385. |
| [70] | Toblli JE, Lombraña A, Duarte P, Di Gennaro F. Intravenous iron reduces NT-pro-brain natriuretic peptide in anemic patients with chronic heart failure and renal insufficiency. J Am Coll Cardiol. 2007; 50 (17): 1657-1665. DOI: 10.1016/j.jacc.2007.07.029. |
| [71] | Drozd M, Jankowska EA, Banasiak W, Ponikowski P. Iron Therapy in Patients with Heart Failure and Iron Deficiency: Review of Iron Preparations for Practitioners. Am J Cardiovasc Drugs. 2017; 17 (3): 183-201. DOI: 10.1007/s40256-016-0211-2. |
| [72] | Kotecha D, Ngo K, Walters JA, Manzano L, Palazzuoli A, Flather MD. Erythropoietin as a treatment of anemia in heart failure: systematic review of randomized trials. Am Heart J. 2011; 161 (5): 822-831.e2. DOI: 10.1016/j.ahj.2011.02.013. |
| [73] | Swedberg K, Young JB, Anand IS, et al. Treatment of anemia with darbepoetin alfa in systolic heart failure. N Engl J Med. 2013; 368 (13): 1210-1219. DOI: 10.1056/NEJMoa1214865. |
| [74] | Yancy CW, Jessup M, Bozkurt B, et al. 2017 ACC/AHA/HFSA Focused Update of the 2013 ACCF/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Card Fail. 2017; 23 (8): 628-651. DOI: 10.1016/j.cardfail.2017.04.014. |
| [75] | Aapro M, Österborg A, Gascón P, Ludwig H, Beguin Y. Prevalence and management of cancer-related anaemia, iron deficiency and the specific role of i.v. iron. Ann Oncol. 2012; 23 (8): 1954-1962. DOI: 10.1093/annonc/mds112. |
| [76] | Caro JJ, Salas M, Ward A, Goss G. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001; 91 (12): 2214-2221. |
| [77] | Goodnough LT, Levy JH, Murphy MF. Concepts of blood transfusion in adults. Lancet. 2013; 381 (9880): 1845-1854. DOI: 10.1016/S0140-6736(13)60650-9. |
| [78] | Vamvakas EC, Blajchman MA. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood. 2009; 113 (15): 3406-3417. DOI: 10.1182/blood-2008-10-167643. |
| [79] | Klein HG. How safe is blood, really?. Biologicals. 2010; 38 (1): 100-104. DOI: 10.1016/j.biologicals.2009.10.008. |
| [80] | Bohlius J, Schmidlin K, Brillant C, et al. Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials [published correction appears in Lancet. 2009 Jul 4-2009 Jul 10; 374 (9683): 28]. Lancet. 2009; 373 (9674): 1532-1542. DOI: 10.1016/S0140-6736(09)60502-X. |
| [81] | Bohlius J, Schmidlin K, Brillant C, et al. Erythropoietin or Darbepoetin for patients with cancer--meta-analysis based on individual patient data. Cochrane Database Syst Rev. 2009; 2009 (3): CD007303. Published 2009 Jul 8. DOI: 10.1002/14651858.CD007303.pub2. |
| [82] | Mhaskar R, Wao H, Miladinovic B, Kumar A, Djulbegovic B. The role of iron in the management of chemotherapy-induced anemia in cancer patients receiving erythropoiesis-stimulating agents. Cochrane Database Syst Rev. 2016; 2: CD009624. Published 2016 Feb 4. DOI: 10.1002/14651858.CD009624.pub2. |
| [83] | Lebrun F, Klastersky J, Levacq D, Wissam Y, Paesmans M. Intravenous iron therapy for anemic cancer patients: a review of recently published clinical studies. Support Care Cancer. 2017; 25 (7): 2313-2319. DOI: 10.1007/s00520-017-3672-1. |
| [84] | Rodgers GM, Gilreath JA. The Role of Intravenous Iron in the Treatment of Anemia Associated with Cancer and Chemotherapy. Acta Haematol. 2019; 142 (1): 13-20. DOI: 10.1159/000496967. |
| [85] | Pandey R, Daloul R, Coyne DW. Iron Treatment Strategies in Dialysis-Dependent CKD. Semin Nephrol. 2016; 36 (2): 105-111. DOI: 10.1016/j.semnephrol.2016.02.004. |
| [86] | Nielsen OH, Ainsworth M, Coskun M, Weiss G. Management of Iron-Deficiency Anemia in Inflammatory Bowel Disease: A Systematic Review. Medicine (Baltimore). 2015; 94 (23): e963. DOI: 10.1097/MD.0000000000000963. |
| [87] | Torres J, Bonovas S, Doherty G, et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment. J Crohns Colitis. 2020; 14 (1): 4-22. DOI: 10.1093/ecco-jcc/jjz180. |
| [88] | Breymann C, Auerbach M. Iron deficiency in gynecology and obstetrics: clinical implications and management. Hematology Am Soc Hematol Educ Program. 2017; 2017 (1): 152-159. DOI: 10.1182/asheducation-2017.1.152. |
| [89] | Bhavi SB, Jaju PB. Intravenous iron sucrose v/s oral ferrous fumarate for treatment of anemia in pregnancy. A randomized controlled trial. BMC Pregnancy Childbirth. 2017; 17 (1): 137. Published 2017 May 8. DOI: 10.1186/s12884-017-1313-9. |
| [90] | 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 (1): 19-29. e3. DOI: 10.1016/j.ajog.2018.12.016. |
| [91] | Avni T, Bieber A, Grossman A, Green H, Leibovici L, Gafter-Gvili A. The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc. 2015; 90 (1): 12-23. DOI: 10.1016/j.mayocp.2014.10.007. |
| [92] | Froessler B, Collingwood J, Hodyl NA, Dekker G. Intravenous ferric carboxymaltose for anaemia in pregnancy. BMC Pregnancy Childbirth. 2014; 14: 115. Published 2014 Mar 25. DOI: 10.1186/1471-2393-14-115. |
| [93] | Girelli D, Ugolini S, Busti F, Marchi G, Castagna A. Modern iron replacement therapy: clinical and pathophysiological insights. Int J Hematol. 2018; 107 (1): 16-30. DOI: 10.1007/s12185-017-2373-3. |
| [94] | Bhandari S, Pereira DIA, Chappell HF, Drakesmith H. Intravenous Irons: From Basic Science to Clinical Practice. Pharmaceuticals (Basel). 2018; 11 (3): 82. Published 2018 Aug 27. DOI: 10.3390/ph11030082. |
| [95] | Hershko C, Skikne B. Pathogenesis and management of iron deficiency anemia: emerging role of celiac disease, helicobacter pylori, and autoimmune gastritis. Semin Hematol. 2009; 46 (4): 339-350. DOI: 10.1053/j.seminhematol.2009.06.002. |
| [96] | Kortman GA, Raffatellu M, Swinkels DW, Tjalsma H. Nutritional iron turned inside out: intestinal stress from a gut microbial perspective. FEMS Microbiol Rev. 2014; 38 (6): 1202-1234. DOI: 10.1111/1574-6976.12086. |
| [97] | Heath CW, Strauss MB, Castle WB. QUANTITATIVE ASPECTS OF IRON DEFICIENCY IN HYPOCHROMIC ANEMIA: (The Parenteral Administration of Iron). J Clin Invest. 1932; 11 (6): 1293-1312. DOI: 10.1172/JCI100478. |
| [98] | Auerbach M, Ballard H. Clinical use of intravenous iron: administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program. 2010; 2010: 338-347. DOI: 10.1182/asheducation-2010.1.338. |
| [99] | Duncan R, Gaspar R. Nanomedicine (s) under the microscope. Mol Pharm. 2011; 8 (6): 2101-2141. DOI: 10.1021/mp200394t. |
| [100] | Auerbach M, Deloughery T. Single-dose intravenous iron for iron deficiency: a new paradigm. Hematology Am Soc Hematol Educ Program. 2016; 2016 (1): 57-66. DOI: 10.1182/asheducation-2016.1.57. |
| [101] | Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmén J. Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant. 2006; 21 (2): 378-382. DOI: 10.1093/ndt/gfi253. |
| [102] | Szebeni J, Fishbane S, Hedenus M, et al. Hypersensitivity to intravenous iron: classification, terminology, mechanisms and management. Br J Pharmacol. 2015; 172 (21): 5025-5036. DOI: 10.1111/bph.13268. |
| [103] | Nguyen KL, Moriarty JM, Plotnik AN, et al. Ferumoxytol-enhanced MR Angiography for Vascular Access Mapping before Transcatheter Aortic Valve Replacement in Patients with Renal Impairment: A Step Toward Patient-specific Care. Radiology. 2018; 286 (1): 326-337. DOI: 10.1148/radiol.2017162899. |
| [104] | Bolton-Maggs PH, Cohen H. Serious Hazards of Transfusion (SHOT) haemovigilance and progress is improving transfusion safety. Br J Haematol. 2013; 163 (3): 303-314. DOI: 10.1111/bjh.12547. |
| [105] | Barton JC, Barton EH, Bertoli LF, Gothard CH, Sherrer JS. 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 (1): 27-32. DOI: 10.1016/s0002-9343(00)00396-x. |
| [106] | Rampton D, Folkersen J, Fishbane S, et al. Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica. 2014; 99 (11): 1671-1676. DOI: 10.3324/haematol.2014.111492. |
| [107] | Szebeni J. Complement activation-related pseudoallergy: a stress reaction in blood triggered by nanomedicines and biologicals. Mol Immunol. 2014; 61 (2): 163-173. DOI: 10.1016/j.molimm.2014.06.038. |
| [108] | Aksan A, Işık H, Radeke HH, Dignass A, Stein J. Systematic review with network meta-analysis: comparative efficacy and tolerability of different intravenous iron formulations for the treatment of iron deficiency anaemia in patients with inflammatory bowel disease. Aliment Pharmacol Ther. 2017; 45 (10): 1303-1318. DOI: 10.1111/apt.14043. |
APA Style
Marshall Patrick Stagg, Jennifer Miatech, Hailey Tarleton. (2020). A Brief Review for Clinicians of Iron Metabolism and the Safety, Efficacy, and Rationale for Use of Intravenous Iron Products. American Journal of Internal Medicine, 8(6), 289-303. https://doi.org/10.11648/j.ajim.20200806.19
ACS Style
Marshall Patrick Stagg; Jennifer Miatech; Hailey Tarleton. A Brief Review for Clinicians of Iron Metabolism and the Safety, Efficacy, and Rationale for Use of Intravenous Iron Products. Am. J. Intern. Med. 2020, 8(6), 289-303. doi: 10.11648/j.ajim.20200806.19
AMA Style
Marshall Patrick Stagg, Jennifer Miatech, Hailey Tarleton. A Brief Review for Clinicians of Iron Metabolism and the Safety, Efficacy, and Rationale for Use of Intravenous Iron Products. Am J Intern Med. 2020;8(6):289-303. doi: 10.11648/j.ajim.20200806.19
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.ajim.20200806.19,
author = {Marshall Patrick Stagg and Jennifer Miatech and Hailey Tarleton},
title = {A Brief Review for Clinicians of Iron Metabolism and the Safety, Efficacy, and Rationale for Use of Intravenous Iron Products},
journal = {American Journal of Internal Medicine},
volume = {8},
number = {6},
pages = {289-303},
doi = {10.11648/j.ajim.20200806.19},
url = {https://doi.org/10.11648/j.ajim.20200806.19},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20200806.19},
abstract = {Iron is an abundant element that is essential for multiple biologic processes. Iron metabolism is not entirely understood, but since the discovery of hepcidin, much progress has been made especially in the last five years. This article is intended to enhance clinician understanding of iron metabolism which may inform decisions about parenteral iron use in iron-restricted erythropoiesis (IResE). This article briefly discusses intravenous (IV) iron utilization in iron deficiency, anemia of chronic inflammation (ACI), functional iron deficiency (FID), and anemia associated with chronic kidney disease, heart failure, pregnancy, inflammatory bowel disease and cancer. Oral iron therapy is valuable in mild to moderate pure iron deficiency. Intravenous iron is required when a prompt response is needed in severe pure iron deficiency. ACI is a hypoferremic state resulting from altered iron metabolism. In ACI, IV iron is needed to overcome the blocking effects of hepcidin on intestinal absorption. ESAs stimulate erythropoiesis increasing iron utilization. This surge in iron requirement can result in FID, especially when ESAs are used in patients with ACI. Intravenous iron is required to treat or avoid iron deficiency in FID when inflammation is present. Parenteral iron maximizes ESA response and can make using erythropoiesis-stimulating agents (ESAs) safer by being ESA sparing. The complex and seemingly ubiquitous nature of iron in humans and the inadequate methods of assessment of iron status in inflammatory states means clinical and laboratory monitoring and individualization of care remain essential. The decision to administer intravenous iron is complex as it often lacks robust consensus guidelines; despite this we can expect utilization of these products to increase as they are safe, effective and necessary.},
year = {2020}
}
TY - JOUR T1 - A Brief Review for Clinicians of Iron Metabolism and the Safety, Efficacy, and Rationale for Use of Intravenous Iron Products AU - Marshall Patrick Stagg AU - Jennifer Miatech AU - Hailey Tarleton Y1 - 2020/11/27 PY - 2020 N1 - https://doi.org/10.11648/j.ajim.20200806.19 DO - 10.11648/j.ajim.20200806.19 T2 - American Journal of Internal Medicine JF - American Journal of Internal Medicine JO - American Journal of Internal Medicine SP - 289 EP - 303 PB - Science Publishing Group SN - 2330-4324 UR - https://doi.org/10.11648/j.ajim.20200806.19 AB - Iron is an abundant element that is essential for multiple biologic processes. Iron metabolism is not entirely understood, but since the discovery of hepcidin, much progress has been made especially in the last five years. This article is intended to enhance clinician understanding of iron metabolism which may inform decisions about parenteral iron use in iron-restricted erythropoiesis (IResE). This article briefly discusses intravenous (IV) iron utilization in iron deficiency, anemia of chronic inflammation (ACI), functional iron deficiency (FID), and anemia associated with chronic kidney disease, heart failure, pregnancy, inflammatory bowel disease and cancer. Oral iron therapy is valuable in mild to moderate pure iron deficiency. Intravenous iron is required when a prompt response is needed in severe pure iron deficiency. ACI is a hypoferremic state resulting from altered iron metabolism. In ACI, IV iron is needed to overcome the blocking effects of hepcidin on intestinal absorption. ESAs stimulate erythropoiesis increasing iron utilization. This surge in iron requirement can result in FID, especially when ESAs are used in patients with ACI. Intravenous iron is required to treat or avoid iron deficiency in FID when inflammation is present. Parenteral iron maximizes ESA response and can make using erythropoiesis-stimulating agents (ESAs) safer by being ESA sparing. The complex and seemingly ubiquitous nature of iron in humans and the inadequate methods of assessment of iron status in inflammatory states means clinical and laboratory monitoring and individualization of care remain essential. The decision to administer intravenous iron is complex as it often lacks robust consensus guidelines; despite this we can expect utilization of these products to increase as they are safe, effective and necessary. VL - 8 IS - 6 ER -
Information
Email: