NDT Advance Access originally published online on September 12, 2006
Nephrology Dialysis Transplantation 2007 22(2):661-662; doi:10.1093/ndt/gfl533
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Severe intravascular haemolysis and acute renal failure following intravenous administration of iron dextran
Email: nhbuus{at}dadlnet.dkSir,
Parenteral administration of iron is occasionally required for treating iron deficiency anaemia in patients with intolerable side effects to, or impaired absorption of, oral iron preparations. However, intravenous administration of iron preparations, as opposed to oral iron, carries a risk of serious adverse reactions [1–3]; the use of iron dextran has especially been associated with allergic reactions [4,5]. Severe haematological adverse reactions to parental iron administration have not been previously published. We report a case of intravascular haemolysis complicated by acute renal failure following iron dextran administration in a woman with previously normal kidney function.
A 40-year-old Arabic woman was, >10 years previously, diagnosed with microcytic anaemia and severe iron deficiency. There were no signs of gastrointestinal haemorrhage or coeliac disease, and haemoglobin electrophoresis was normal. Oral iron supplementation was repeatedly tried but always stopped because of adverse gastrointestinal effects. Concomitant medication consisted of amlodipine, sertraline and occasionally sumatriptan. Due to intolerable side effects of oral iron, the patient was administered intravenous low molecular weight iron dextran (Cosmofer®) at a slow infusion rate. Shortly after commencing the infusion, the patient developed anxiety, chest discomfort and a decrease in blood pressure and heart rate. The infusion was stopped and she was treated with intravenous hydrocortisone and quickly recovered. Four weeks later she received two erythrocyte transfusions. The next day, a new attempt was made to treat the patient with iron dextran. Again, she developed anxiety and chest pain without any change in blood pressure or signs of bronchospasms. Again she received intravenous hydrocortisone and clemastine as well as sublingual nitroglycerine. Within 5 min of withholding the infusion, all symptoms disappeared. After 7 days, she was readmitted to hospital with back pain and almost black urine. Blood tests revealed acute renal failure with creatinine rising from 43 to 458 µmol/l within 1 week. Moreover, there were signs of haemolysis with increased levels of lactate dehydrogenase, immeasurable low levels of haptoglobin and very high levels of free haemoglobin in plasma. Coombs test was negative and no erythrocyte antibodies could be detected. Schistocytes could not be identified at blood microscopy. Biochemical screening revealed no antineutrophil cytoplasmic antibodies and the levels of immunoglobulins and complement factors were normal. The number of blood eosinophils was normal. The platelet number decreased from 422 x 109/l to 212 x 109/l at admission and then remained within the reference level. Antibody screening showed no signs of viral infection. Ultrasound examination of the kidneys revealed no abnormalities. A renal biopsy was not performed. Within 24 h after admission, she developed anuria and haemodialysis was initiated. Due to the slight reduction in platelet count, the patient was at first suspected of a microangiopathic haemolytic anaemia and plasma exchange was performed with substitution with fresh frozen plasma. For the next 18 days she received nine haemodialysis treatments, six plasma exchanges and 14 erythrocyte transfusions. During this period haemolysis ceased and the patient regained kidney function. Two months later she had normal kidney function with creatinine clearance of 116 ml/min and no signs of haemolysis.
The epidemiology of iron dextran hypersensitivity is well characterized [1–3], and it is well known that the drug may elicit a hypersensitivity reaction at the first exposure. Severe allergic reactions to iron dextran consist mainly of respiratory and cardiovascular symptoms. The presented patient twice demonstrated such typical immediate hypersensitivity symptoms, although these were relatively mild and easily reversed by hydrocortisone. The patient had not received any new medication and there were no signs of infections or other exogeneous reasons known to induce acute severe haemolysis. Although the patient at the time of admission was suspected of microangiopathic haemolysis, there were insufficient biochemical findings supporting this diagnosis. Only a few days passed from the second exposure to iron dextran to when the patient developed haemolysis, and the condition can almost certainly be ascribed to iron dextran exposure. There are no previous published reports on haemolysis associated with infusion of iron preparations, but the World Health Organization's (WHO) Adverse Reaction Database (Uppsala Monitoring Centre) describes two patients with haemolysis probably due to iron dextran. However, the database also reports three patients with haemolysis due to iron gluconate treatment, suggesting that the reactions may not be related to a specific iron complex.
The mechanisms behind iron dextran-induced haemolysis in the presented patient are unknown. Several drugs can act as haptens and may, through their binding to specific erythrocyte receptors, induce production of complement-activating antibodies mediating severe extra- or intravascular haemolysis. Although intravenous administered iron complexes have not previously been implicated in immunological mediated haemolysis, the time frame for this mechanism is typically 1–2 weeks from the first drug exposure to active haemolysis, as was seen in our patient.
Conflict of interest statement. None declared.
Department of Renal Medicine
Aarhus University Hospital
Denmark
References
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[Abstract/Free Full Text] - Faich G and Strobos J. (1999) Sodium ferric gluconate complex in sucrose: safer intravenous iron therapy than iron dextrans. Am J Kidney Dis 33:464–470.[Web of Science][Medline]
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