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• The issue of non-anaemic iron deficiency
  oscar,m jolobe
  Published on: 28 November 2019

• Published on: 28 November 2019

  The issue of non-anaemic iron deficiency

  • oscar,m jolobe, retired geriatrician manchester medical society

  The heading which reads "Heart failure with Reduced Ejection Fraction(LVEF < 40%) & Iron Deficiency Anaemia"(fig 1)(1) fails. by implication, to recognise that heart failure-related iron deficiency has an outcome which is detrimental irrespective of whether or not the patient is anaemic(2). In the latter study, among heart failure patients who had a marker of iron deficiency(ID), namely, mean corpuscular haemoglobin concentration(MCHC) equal to or less than 330 g/L, there was a significant association with increased mortality(Hazard Ratio 1.7, 95% Confidence Interval 1.4 to 2.0) which persisted even after adjusting for anaemia(HR 1.5, 95% CI 1.3 to 1.8)(2). The use of the cut-off MCHC value of 330 g/L or less as a marker of ID (1) is supported by studies where mean values for MCHC amounted to 319 g/L and 327.9 g/L, respectively, among subjects with ID(3)(4). In those two studies the iron-replete subjects were characterised by MCHC values amounting to 339 g/L and 340 g/L, respectively. The mean values for MCHC in ID subjects(namely, 319 g/L and 327.9 g/L, respectively) were significantly(p=0.001, p < 0.001) lower than the mean values for MCHC(339 g/L and 340 g L, respectively) in their iron-replete counterparts. In those two studies, as well, mean values for mean corpuscular volume(MCV) in ID subjects ranged from 85.5 fl to 90.2 fl in spite of proven ID(serum ferritin < 30 mcg/L) and MCHC < 330 g/L. Accordingly, to optimise the i...

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  The heading which reads "Heart failure with Reduced Ejection Fraction(LVEF < 40%) & Iron Deficiency Anaemia"(fig 1)(1) fails. by implication, to recognise that heart failure-related iron deficiency has an outcome which is detrimental irrespective of whether or not the patient is anaemic(2). In the latter study, among heart failure patients who had a marker of iron deficiency(ID), namely, mean corpuscular haemoglobin concentration(MCHC) equal to or less than 330 g/L, there was a significant association with increased mortality(Hazard Ratio 1.7, 95% Confidence Interval 1.4 to 2.0) which persisted even after adjusting for anaemia(HR 1.5, 95% CI 1.3 to 1.8)(2). The use of the cut-off MCHC value of 330 g/L or less as a marker of ID (1) is supported by studies where mean values for MCHC amounted to 319 g/L and 327.9 g/L, respectively, among subjects with ID(3)(4). In those two studies the iron-replete subjects were characterised by MCHC values amounting to 339 g/L and 340 g/L, respectively. The mean values for MCHC in ID subjects(namely, 319 g/L and 327.9 g/L, respectively) were significantly(p=0.001, p < 0.001) lower than the mean values for MCHC(339 g/L and 340 g L, respectively) in their iron-replete counterparts. In those two studies, as well, mean values for mean corpuscular volume(MCV) in ID subjects ranged from 85.5 fl to 90.2 fl in spite of proven ID(serum ferritin < 30 mcg/L) and MCHC < 330 g/L. Accordingly, to optimise the identification of ID(irrespective of coexistence of anaemia), the screening test should be an MCHC of 330 g/L or lower(ideally < 330 g/L). To confirm the diagnosis of ID the next step should be evaluation of serum ferritin and transferrin saturation, respectively.
  With regard to treatment, for the non-anaemic ID patient the optimum treatment should be either intravenous iron(1) or oral iron taken as a single dose on alternate days(5). The latter is an innovation which optimises iron absorption in nonanaemic ID subjects who do not have heart failure(5). It is reasonable to extrapolate the efficacy of that dosing regime to heart failure patients with non-anaemic ID if they cannot tolerate intravenous iron. Whether or not that regime optimises iron absorption in the anaemic phase of ID remains to be proven by future studies. I agree that anaemic subjects with ID should receive intravenous iron. In the presence of heart failure and intolerance of intravenous iron it is unproven whether or not the dosing regime of Stoffel et al(5) would be appropriate.
  Finally, although the guideline appears to confine its recommendation for further investigation only to patients who are in the anaemic phase of ID(final paragraph of fig 1)(1), it seems logical to investigate the underlying cause of ID regardless of whether or not the patient is anaemic. After all, anaemia is a manifestation of ID which occurs relatively late in the natural history of the underlying cause of ID. Furthermore, the underlying cause of ID needs to be eliminated even in the absence of anaemia.
  I have no funding and no conflict of interest
  References
  (1) Simon S., Ioannou A., Deora S et al
  Audit of the prevalence and investigation of iron deficiency anaemia in patients with heart failure in hospital practice
  Postgrad Med J 2019;doi:10.1136/postgradmedj-2019-136867
  (2)Kleber M., Kozhuharov N., Sabti Z et al
  Relative hypochromia and mortality in acute heart failure
  Int J Cardiol 2019;286:104-110
  (3) Urrechaga E., Borque L., Escanero JF
  Clinical value of hypochromia markers in the detection of latent iron deficiency in non-anaemic premenopausal women
  Journal of Clinical Laboratory Analysis 2016;30:623-726
  (4) Malczewska -Leneczowska J., Orysiak J et al
  Reticulocyte and erythrocyte hypochromia markers in detection of iron deficiency in adolescent female athletes
  Biol Sport 2017;34:111-118
  (5)Stoffel N., Cercamondi C., Brittenham G et al
  Iron absorption from oral iron supplements given on consecutive days versus alternate days and as a single dose versus twice-daily dosing in iron depleted women, two open-label, randomised controlled trials
  Lancet Haematol 2017;4:524-533

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  Conflict of Interest:
  None declared.

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