Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management

Intravenous iron is widely used for the treatment of iron deficiency anemia when oral iron is inappropriate, ineffective or poorly tolerated. Acute hypersensitivity reactions during iron infusions are very rare but can be life-threatening. This paper reviews their frequency, pathogenesis and risk factors, and provides recommendations about their management and prevention. Complement activation-related pseudo-allergy triggered by iron nanoparticles is probably a more frequent pathogenetic mechanism in acute reactions to current formulations of intravenous iron than is an immunological IgE-mediated response. Major risk factors for hypersensitivity reactions include a previous reaction to an iron infusion, a fast iron infusion rate, multiple drug allergies, severe atopy, and possibly systemic inflammatory diseases. Early pregnancy is a contraindication to iron infusions, while old age and serious co-morbidity may worsen the impact of acute reactions if they occur. Management of iron infusions requires meticulous observation, and, in the event of an adverse reaction, prompt recognition and severity-related interventions by well-trained medical and nursing staff.

[1]  J. Ring,et al.  INCIDENCE AND SEVERITY OF ANAPHYLACTOID REACTIONS TO COLLOID VOLUME SUBSTITUTES , 1977, The Lancet.

[2]  N. Vaziri,et al.  Immunologic studies of anaphylaxis to iron dextran in patients on renal dialysis. , 1994, Annals of allergy.

[3]  J. Glaspy,et al.  Clinical update: intravenous iron for anaemia , 2007, The Lancet.

[4]  G. Bailie Comparison of rates of reported adverse events associated with i.v. iron products in the United States. , 2012, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[5]  E F Ring,et al.  Effect of intravenous iron dextran on rheumatoid synovitis. , 1985, Annals of the rheumatic diseases.

[6]  W. Vogel Infusion reactions: diagnosis, assessment, and management. , 2010, Clinical journal of oncology nursing.

[7]  S. Brown Clinical features and severity grading of anaphylaxis. , 2004, The Journal of allergy and clinical immunology.

[8]  J. Critchley,et al.  Adverse events associated with intravenous iron infusion (low-molecular-weight iron dextran and iron sucrose): a systematic review , 2007 .

[9]  A. Sheikh,et al.  World Allergy Organization Guidelines for the Assessment and Management of Anaphylaxis , 2011, The World Allergy Organization journal.

[10]  F. Heupler,et al.  Systemic anaphylactoid reactions to iodinated contrast media during cardiac catheterization procedures: guidelines for prevention, diagnosis, and treatment. Laboratory Performance Standards Committee of the Society for Cardiac Angiography and Interventions. , 1995, Catheterization and cardiovascular diagnosis.

[11]  J. Soar,et al.  Emergency treatment of anaphylactic reactions--guidelines for healthcare providers. , 2008, Resuscitation.

[12]  L. Cuervo,et al.  Treatments for iron-deficiency anaemia in pregnancy. , 2011, The Cochrane database of systematic reviews.

[13]  Janos Szebeni,et al.  Complement activation-related pseudoallergy: a new class of drug-induced acute immune toxicity. , 2005, Toxicology.

[14]  G. Elwyn,et al.  One hundred years ago: Should milk be boiled? , 2002, BMJ : British Medical Journal.

[15]  M. Auerbach,et al.  Clinical use of intravenous iron: administration, efficacy, and safety. , 2010, Hematology. American Society of Hematology. Education Program.

[16]  U. Kolb,et al.  A comparative study of the physicochemical properties of iron isomaltoside 1000 (Monofer), a new intravenous iron preparation and its clinical implications. , 2011, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[17]  Catherine M. Dormitzer,et al.  Use of parenteral iron products and serious anaphylactic‐type reactions , 2010, American journal of hematology.

[18]  J. Szebeni Hemocompatibility testing for nanomedicines and biologicals: predictive assays for complement mediated infusion reactions , 2012 .

[19]  S. Fishbane,et al.  The safety of intravenous iron dextran in hemodialysis patients. , 1996, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[20]  F. Heupler,et al.  Systemic anaphylactoid reactions to lodinated contrast media during cardiac catheterization procedures: Guidelines for prevention, diagnosis, and treatment , 1995 .

[21]  W. Winkelmayer,et al.  A possible new role for Helicobacter pylori in the development of ocular adnexal lymphoma , 2010, American journal of hematology.

[22]  G. Bailie,et al.  Differences in the reporting rates of serious allergic adverse events from intravenous iron by country and population. , 2012, Clinical advances in hematology & oncology : H&O.

[23]  L. Cuervo,et al.  Treatments for iron deficiency anaemia in pregnancy. , 2001, The Cochrane database of systematic reviews.

[24]  D. Steensma,et al.  Should the ASCO/ASH Guidelines for the use of intravenous iron in cancer- and chemotherapy-induced anemia be updated? , 2014, Journal of the National Comprehensive Cancer Network : JNCCN.

[25]  Thomas Bieber,et al.  Revised nomenclature for allergy for global use: Report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. , 2004, The Journal of allergy and clinical immunology.

[26]  V. Runge,et al.  Safety of magnetic resonance contrast media. , 2001, Topics in magnetic resonance imaging : TMRI.

[27]  G. Chertow,et al.  Update on adverse drug events associated with parenteral iron. , 2006, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[28]  J. Ring,et al.  Anaphylaxis: acute treatment and management. , 2010, Chemical immunology and allergy.

[29]  M. Bodó,et al.  Complement activation-related cardiac anaphylaxis in pigs: role of C5a anaphylatoxin and adenosine in liposome-induced abnormalities in ECG and heart function. , 2006, American journal of physiology. Heart and circulatory physiology.

[30]  G. Schett,et al.  Anaemia in inflammatory rheumatic diseases , 2013, Nature Reviews Rheumatology.

[31]  J. Strong,et al.  UK guidelines on the management of iron deficiency in pregnancy , 2012, British journal of haematology.

[32]  D. Parratt,et al.  Dextran antibodies, complement conversion and circulating immune complexes after intravenous iron dextran therapy in dialysed patients. , 1992, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.