Advertisement

The diagnostic trial of iron replacement therapy even in normocytic anaemia

Published:August 09, 2017DOI:https://doi.org/10.1016/j.ejim.2017.08.007
      Among the diagnostic strategies for validating the provisional diagnosis of iron deficiency anaemia (IDA) [
      • De Franceschi L.
      • Iolascon A.
      • Taher A.
      • Cappellini M.D.
      Clinical management of iron deficiency anaemia in adults: systemic review on advances in diagnosis and treatment.
      ] one parameter worth including is the response to a diagnostic trial of iron replacement therapy [
      • Freire W.B.
      Hemoglobin as a predictor of response to iron therapy and its use in screening and prevalence estimates.
      ,
      • Okam M.M.
      • Koch T.A.
      • Tran M.-H.
      Iron supplementation, response in iron deficiency anaemia: analysis of five trials.
      ,
      • Onken J.E.
      • Bregman D.B.
      • Harrinton R.A.
      • et al.
      A multicentre, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia.
      ], which could be utilised even in subjects with normocytic iron deficiency anaemia [
      • Ho J.C.L.
      • Chan A.K.C.
      • Lau K.K.
      • Chan H.H.W.
      Iron deficiency as a common treatable cause of normocytic anemia.
      ]. 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 [
      • Goodnough L.T.
      • Nemeth E.
      • Ganz T.
      Detection, evaluation, and management of iron restricted erythropoiesis.
      ]. 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 [
      • Okam M.M.
      • Koch T.A.
      • Tran M.-H.
      Iron supplementation, response in iron deficiency anaemia: analysis of five trials.
      ]. 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 [
      • Onken J.E.
      • Bregman D.B.
      • Harrinton R.A.
      • et al.
      A multicentre, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia.
      ]. 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 [
      • Onken J.E.
      • Bregman D.B.
      • Harrinton R.A.
      • et al.
      A multicentre, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia.
      ]. The occurrence of serious side effects (including hypersensitivity reactions and hypotension) in up to 6.7% of patients receiving intravenous iron [
      • Onken J.E.
      • Bregman D.B.
      • Harrinton R.A.
      • et al.
      A multicentre, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia.
      ] does, however, continue to be a limiting factor to the widespread use of this modality.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to European Journal of Internal Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • De Franceschi L.
        • Iolascon A.
        • Taher A.
        • Cappellini M.D.
        Clinical management of iron deficiency anaemia in adults: systemic review on advances in diagnosis and treatment.
        Eur J Intern Med. 2017; 42: 16-23
        • Freire W.B.
        Hemoglobin as a predictor of response to iron therapy and its use in screening and prevalence estimates.
        Am J Clin Nutr. 1989; 50: 1442-1449
        • Okam M.M.
        • Koch T.A.
        • Tran M.-H.
        Iron supplementation, response in iron deficiency anaemia: analysis of five trials.
        Am J Med. 2017; 130: 991.e1-991.e8
        • Onken J.E.
        • Bregman D.B.
        • Harrinton R.A.
        • et al.
        A multicentre, randomized, active-controlled study to investigate the efficacy and safety of intravenous ferric carboxymaltose in patients with iron deficiency anemia.
        Transfusion. 2014; 54: 306-315
        • Ho J.C.L.
        • Chan A.K.C.
        • Lau K.K.
        • Chan H.H.W.
        Iron deficiency as a common treatable cause of normocytic anemia.
        Blood. 2014; 124: 4032
        • Goodnough L.T.
        • Nemeth E.
        • Ganz T.
        Detection, evaluation, and management of iron restricted erythropoiesis.
        Blood. 2010; 116: 4754-4761
        • Panagiotopoulou I.G.
        • Fitzrol D.
        • Parker R.A.
        • et al.
        The yield of colorectal cancer among fast track patients with normocytic and microcytic anaemia.
        Ann R Coll Surg Engl. 2014; 96: 289-293