Clinical update: intravenous iron for anaemia.

For nearly half a century, parenteral iron has been considered dangerous and for use only in extreme situations and when oral iron was not tolerated. This proscription was based largely on poorly characterised and infrequent anaphylactoid reactions to the high-molecular-weight dextran preparation (Imferon) that for most of this time was the only product available. Moreover, when parenteral iron was necessary, the recommended approach was small intramuscular doses (≤100 mg), even after intravenous administration of the total iron defi cit as a single dose or as repetitive boluses was shown to be as safe and eff ective as the intramuscular route. This mindset persists despite the subsequent introduction of low-molecular-weight iron dextran and two iron salt preparations, ferric gluconate and iron saccharate (the latter is also known as iron sucrose), all of which are associated with fewer serious adverse events than the high-molecular-weight dextran. The introduction of recombinant erythropoietin for dialysis patients was associated with the development, in some individuals, of functional iron defi ciency that limited effi cacy. Intravenous iron, unlike oral iron, improves erythropoietic response in dialysis patients, and is now routinely used. The discovery of the iron regulatory peptide, hepcidin, has improved our understanding of the anaemia of chronic infl ammatory states, including cancer. Hepcidin is upregulated in these conditions, resulting in increased synthesis by the liver. Hepcidin inhibits iron transport across cell membranes, which decreases the accessibility of storage iron and gastrointestinal absorption of dietary iron, leading to an increased frequency of iron-restricted erythropoiesis, especially during therapy with recombinant erythropoietin. The most frequent laboratory fi ndings during the anaemia of chronic infl ammation are hypoferraemia and a low percent transferrin saturation, although these fi ndings are not always present. The increasing use of recombinant erythropoietin to treat anaemia in patients with chronic diseases has expanded the population of patients with functional iron defi ciency and increased interest in safe rational approaches to parenteral iron therapy. There is mounting evidence that anaemic patients with cancer undergoing chemotherapy and receiving recombinant erythropoietin respond better when parenteral iron is administered. This benefi t is independent of baseline iron variables, such as ferritin, low percentage transferrin saturation, and stainable marrow haemosiderin, leaving the clinician in need of laboratory variables to reliably detect iron-restricted erythropoiesis in patients with infl ammatory illnesses and to predict improvement of erythropoietic response to parenteral iron in the setting of infl ammatory illness. Two new laboratory measures look promising: percent hypochromic red blood cells and reticulocyte haemoglobin content. These tests are reliable and accurate correlates of functional iron defi ciency. Although these investigations are not yet widely available, their use will probably expand and guide identifi cation of functional iron defi ciency and rational intervention with parenteral iron. Currently, four parenteral iron preparations are available (table). No randomised trials have compared the safety and effi cacy of any of these agents. The largest retrospective review of dialysis experience suggests that most serious adverse events have been associated with the high-molecular-weight iron dextrans (Imferon, which is no longer available and the current preparation, Dexferrum) and are rare (<1:200 000) with the low-molecular-weight iron dextran or the two iron salts (fi gure). Adverse event rates might be somewhat higher in patients with infl ammatory diseases in which immune-mediated drug reactions may be observed more commonly than in dialysis patients. Some of the adverse clinical experience with parenteral iron is due to inappropriate supportive care. Myalgias, when they include chest and back discomfort, are mistakenly described as anaphylaxis, prompting Low–molecular–weight iron dextran Iron saccharate Ferric gluconate High–molecular–weight iron dextran