The diagnostic trial of iron replacement therapy even in normocytic anaemia

Among the diagnostic strategies for validating the provisional diagnosis of iron deficiency anaemia (IDA) [ ] one parameter worth including is the response to a diagnostic trial of iron replacement therapy [ , , ], which could be utilised even in subjects with normocytic iron deficiency anaemia [ ]. However, in the context of coexisting chronic inflammation, failure to respond to a trial of oral iron does not rule out IDA because inflammatory hepcidin elevation would impair iron absorption [ ]. In order to overcome this disadvantage a two-stage diagnostic trial has been proposed. The initial stage consists of oral replacement therapy whereby a 1.0 g/dl increment in haemoglobin (Hb) on day 14 of treatment is taken as the defining feature of IDA, in conjunction with a 2 g/dl or more increment in Hb (compared with baseline) on day 42 or 56. Of note, a 1 g/dl or more increment in Hb on day 14 was shown to have 90.1% sensitivity, 79.3% specificity, and 92.9% positive predictive value for identifying patients who subsequently proved to have a 2 g/dl or more increment in Hb (compared with baseline) on day 42 or 56 [ ]. In the event that the response to oral iron is suboptimal on day 14, a subsequent trial of intravenous iron has been proposed to identify which of the nonresponders truly have IDA [ ]. In the latter study the nonresponders who subsequently received intravenous iron (instead of oral iron) experienced significantly (p = 0.001) greater increments in Hb than nonresponders who continued to take only oral iron for an additional 14 days. The consequence was that the intravenous iron subgroup experienced increments in Hb nearly twice the increments documented in nonresponders who continued to take only oral iron for a further 14 days [ ]. The occurrence of serious side effects (including hypersensitivity reactions and hypotension) in up to 6.7% of patients receiving intravenous iron [ ] does, however, continue to be a limiting factor to the widespread use of this modality.