Treatment with ferric carboxymaltose in stable patients with severe iron deficiency anemia in the emergency department

Abstract

The AABB Choosing Wisely Campaign recommends “don’t transfuse for iron deficiency without hemodynamic instability”. However, the management of iron deficiency anemia (IDA) in the emergency department (ED) is heterogeneous and patients are often over-transfused. Intravenous iron is effective in correcting anemia and new formulations, including ferric carboxymaltose (FCM), allow the administration of high doses with low immunogenicity. The aim of this retrospective study was to analyze the management of hemodynamically stable patients aged 18–55 years with severe IDA (hemoglobin < 8 g/dL), who presented to the ED from January 2014 to July 2018. Patients who received FCM (FCM1) and those who did not receive FCM (FCM0) were compared. Efficacy and safety of FCM at follow-up were evaluated. Seventy-one subjects fulfilled the inclusion criteria (FCM0 n = 48; FCM1 n = 23). The mean Hb at admission was 6.6 g/dL. 40% in the FCM0 and 13% in FCM1 were transfused (p = 0.02). 21% of FCM0 patients were admitted to the ward, while all FCM1 were discharged (p = 0.02). Within 2 weeks, the Hb increase was 2.8 ± 1 g/dL in the FCM1 group. Sixteen FCM1 patients were evaluated at 52 ± 28 days (median 42, range 27–122): the average Hb increase was 5.3 ± 1.4 g/dL. In summary, we showed that FCM administration in the ED in hemodynamically stable patients was associated with fewer transfusions and hospital admissions compared to the FCM0 group; moreover, it succeeded in safely, effectively and rapidly increasing Hb levels after discharge from the ED. Further studies are needed to develop recommendations for IDA in the ED and to identify transfusion thresholds for non-hospitalized patients.

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References

  1. 1.

    Kassebaum NJ, Jasrasaria R, Naghavi M, Wulf SK, Johns N, Lozano R, Regan M, Weatherall D, Chou DP, Eisele TP, Flaxman SR, Pullan RL, Brooker SJ, Murray CJ (2014) A systematic analysis of global anemia burden from 1990 to 2010. Blood 123(5):615–624. https://doi.org/10.1182/blood-2013-06-508325

    CAS  Article  PubMed Central  Google Scholar 

  2. 2.

    Spradbrow J, Lin Y, Shelton D, Callum J (2017) Iron deficiency anemia in the emergency department: over-utilization of red blood cell transfusion and infrequent use of iron supplementation. CJEM 19(3):167–174. https://doi.org/10.1017/cem.2016.388

    Article  Google Scholar 

  3. 3.

    Goodnough LT, Levy JH, Murphy MF (2013) Concepts of blood transfusion in adults. Lancet 381(9880):1845–1854. https://doi.org/10.1016/S0140-6736(13)60650-9

    Article  Google Scholar 

  4. 4.

    Rohrig G, Steinmetz T, Stein J, Geisel T, Virgin G, Schaefer R, Bach M, Schulz RJ (2014) Efficacy and tolerability of ferric carboxymaltose in geriatric patients with anemia. Data from three non-interventional studies. MMW Fortschr Med 156(Suppl 2):48–53

    Article  Google Scholar 

  5. 5.

    Pusic MV, Dawyduk BJ, Mitchell D (2005) Opportunistic screening for iron-deficiency in 6–36 month old children presenting to the Paediatric Emergency Department. BMC Pediatr 5:42. https://doi.org/10.1186/1471-2431-5-42

    Article  PubMed Central  Google Scholar 

  6. 6.

    Carson JL, Triulzi DJ, Ness PM (2017) Indications for and adverse effects of red-cell transfusion. N Engl J Med 377(13):1261–1272. https://doi.org/10.1056/NEJMra1612789

    Article  Google Scholar 

  7. 7.

    Klein HG, Hrouda JC, Epstein JS (2017) Crisis in the sustainability of the U.S. blood system. N Engl J Med 377(15):1485–1488. https://doi.org/10.1056/NEJMsb1706496

    Article  Google Scholar 

  8. 8.

    Carson JL, Guyatt G, Heddle NM, Grossman BJ, Cohn CS, Fung MK, Gernsheimer T, Holcomb JB, Kaplan LJ, Katz LM, Peterson N, Ramsey G, Rao SV, Roback JD, Shander A, Tobian AA (2016) Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage. JAMA 316(19):2025–2035. https://doi.org/10.1001/jama.2016.9185

    Article  Google Scholar 

  9. 9.

    Callum JL, Waters JH, Shaz BH, Sloan SR, Murphy MF (2014) The AABB recommendations for the choosing wisely campaign of the American Board of Internal Medicine. Transfusion 54(9):2344–2352. https://doi.org/10.1111/trf.12802

    Article  Google Scholar 

  10. 10.

    Khadadah F, Callum J, Shelton D, Lin Y (2018) Improving quality of care for patients with iron deficiency anemia presenting to the emergency department. Transfusion 58(8):1902–1908. https://doi.org/10.1111/trf.14626

    Article  Google Scholar 

  11. 11.

    Beverina I, Brando B (2019) Prevalence of anemia and therapeutic behavior in the emergency department at a tertiary care Hospital: Are patient blood management principles applied? Transfus Apher Sci. https://doi.org/10.1016/j.transci.2019.07.006

    Article  Google Scholar 

  12. 12.

    Camaschella C (2017) New insights into iron deficiency and iron deficiency anemia. Blood Rev 31(4):225–233. https://doi.org/10.1016/j.blre.2017.02.004

    CAS  Article  Google Scholar 

  13. 13.

    Auerbach M, Deloughery T (2016) Single-dose intravenous iron for iron deficiency: a new paradigm. Hematol Am Soc Hematol Educ Progr 2016(1):57–66. https://doi.org/10.1182/asheducation-2016.1.57

    Article  Google Scholar 

  14. 14.

    Wang C, Graham DJ, Kane RC, Xie D, Wernecke M, Levenson M, MaCurdy TE, Houstoun M, Ryan Q, Wong S, Mott K, Sheu TC, Limb S, Worrall C, Kelman JA, Reichman ME (2015) Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA 314(19):2062–2068. https://doi.org/10.1001/jama.2015.15572

    CAS  Article  Google Scholar 

  15. 15.

    Girelli D, Ugolini S, Busti F, Marchi G, Castagna A (2018) Modern iron replacement therapy: clinical and pathophysiological insights. Int J Hematol 107(1):16–30. https://doi.org/10.1007/s12185-017-2373-3

    CAS  Article  Google Scholar 

  16. 16.

    Van Wyck DB, Mangione A, Morrison J, Hadley PE, Jehle JA, Goodnough LT (2009) Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion 49(12):2719–2728. https://doi.org/10.1111/j.1537-2995.2009.02327.x

    CAS  Article  Google Scholar 

  17. 17.

    Evstatiev R, Marteau P, Iqbal T, Khalif IL, Stein J, Bokemeyer B, Chopey IV, Gutzwiller FS, Riopel L, Gasche C, Group FS (2011) FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology 141(3):846–853. https://doi.org/10.1053/j.gastro.2011.06.005

    CAS  Article  PubMed Central  Google Scholar 

  18. 18.

    Macdougall IC, Bock AH, Carrera F, Eckardt KU, Gaillard C, Van Wyck D, Roubert B, Nolen JG, Roger SD, Investigators F-CS (2014) FIND-CKD: a randomized trial of intravenous ferric carboxymaltose versus oral iron in patients with chronic kidney disease and iron deficiency anaemia. Nephrol Dial Transpl 29(11):2075–2084. https://doi.org/10.1093/ndt/gfu201

    CAS  Article  Google Scholar 

  19. 19.

    Kim YW, Bae JM, Park YK, Yang HK, Yu W, Yook JH, Noh SH, Han M, Ryu KW, Sohn TS, Lee HJ, Kwon OK, Ryu SY, Lee JH, Kim S, Yoon HM, Eom BW, Choi MG, Kim BS, Jeong O, Suh YS, Yoo MW, Lee IS, Jung MR, An JY, Kim HI, Kim Y, Yang H, Nam BH, Group FS (2017) Effect of intravenous ferric carboxymaltose on hemoglobin response among patients with acute isovolemic anemia following gastrectomy: the FAIRY randomized clinical trial. JAMA 317(20):2097–2104. https://doi.org/10.1001/jama.2017.5703

    CAS  Article  PubMed Central  Google Scholar 

  20. 20.

    Bisbe E, Garcia-Erce JA, Diez-Lobo AI, Munoz M (2011) A multicentre comparative study on the efficacy of intravenous ferric carboxymaltose and iron sucrose for correcting preoperative anaemia in patients undergoing major elective surgery. Anaemia Working Group E Br J Anaesth 107(3):477–478. https://doi.org/10.1093/bja/aer242

    CAS  Article  Google Scholar 

  21. 21.

    Quintana-Diaz M, Fabra-Cadenas S, Gomez-Ramirez S, Martinez-Virto A, Garcia-Erce JA, Munoz M (2016) A fast-track anaemia clinic in the Emergency Department: feasibility and efficacy of intravenous iron administration for treating sub-acute iron deficiency anaemia. Blood Transfus 14(2):126–133. https://doi.org/10.2450/2015.0176-15

    Article  PubMed Central  Google Scholar 

  22. 22.

    Shander A, Fink A, Javidroozi M, Erhard J, Farmer SL, Corwin H, Goodnough LT, Hofmann A, Isbister J, Ozawa S, Spahn DR, International Consensus Conference on Transfusion Outcomes G (2011) Appropriateness of allogeneic red blood cell transfusion: the international consensus conference on transfusion outcomes. Transfus Med Rev 25(3):232–246. https://doi.org/10.1016/j.tmrv.2011.02.001

    Article  Google Scholar 

  23. 23.

    Wolf M, Chertow GM, Macdougall IC, Kaper R, Krop J, Strauss W (2018) Randomized trial of intravenous iron-induced hypophosphatemia. JCI Insight. https://doi.org/10.1172/jci.insight.124486

    Article  PubMed Central  Google Scholar 

  24. 24.

    Zoller H, Schaefer B, Glodny B (2017) Iron-induced hypophosphatemia: an emerging complication. Curr Opin Nephrol Hypertens 26(4):266–275. https://doi.org/10.1097/MNH.0000000000000329

    CAS  Article  PubMed Central  Google Scholar 

  25. 25.

    Leuenberger N, Barras L, Nicoli R, Robinson N, Baume N, Lion N, Barelli S, Tissot JD, Saugy M (2016) Hepcidin as a new biomarker for detecting autologous blood transfusion. Am J Hematol 91(5):467–472. https://doi.org/10.1002/ajh.24313

    CAS  Article  Google Scholar 

  26. 26.

    Quintana-Diaz M, Munoz-Romo R, Gomez-Ramirez S, Pavia J, Borobia AM, Garcia-Erce JA, Munoz M (2017) A fast-track anaemia clinic in the Emergency Department: cost-analysis of intravenous iron administration for treating iron-deficiency anaemia. Blood Transfus 15(5):438–446. https://doi.org/10.2450/2017.0282-16

    Article  PubMed Central  Google Scholar 

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Authors

Contributions

Irene Motta, Giulia Mantovan, Dario Consonni, Nicola Montano and Maria Domenica Cappellini contributed to the study conception and design. Material preparation, data collection and analysis were performed by Giulia Mantovan, Irene Motta and Dario Consonni. Irene Motta, Anna Maria Brambilla, Maria Materia, Marianna Porzio and Margherita Migone De Amicis took care of patients. The first draft of the manuscript was written by Irene Motta and Giulia Mantovan and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Irene Motta.

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Conflict of interest

IM received honoraria from Sanofi-Genzyme; NM received honoraria for lecturing from Novo Nordisk; MDC member of Vifor, Sanofi-Genzyme, Celgene, Novartis and Bluebird advisory Board.

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This study was approved by the Institutional Ethics Committee of our institution.

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Motta, I., Mantovan, G., Consonni, D. et al. Treatment with ferric carboxymaltose in stable patients with severe iron deficiency anemia in the emergency department. Intern Emerg Med 15, 629–634 (2020). https://doi.org/10.1007/s11739-019-02223-z

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Keywords

  • Severe anemia
  • Iron deficiency
  • Ferric carboxymaltose
  • Transfusion
  • Choosing wisely