Maintenance of the red cell volume is a fundamental aspect of ensuring oxygen supply to the tissues. The balance between the very dynamic processes of erythropoiesis and erythrocyte loss is precarious and yet normal individuals experience a remarkably constant haematocrit. This is achieved by a very elegant and sensitive homeostatic mechanism which links tissue oxygen delivery to red cell production. The glycoprotein hormone erythropoietin (EPO) is the principle controller of this process. It is now clear that even minor underproduction of EPO will result in anaemia. The most widespread example of this is the anaemia of end-stage renal failure. The pharmacological use of recombinant human EPO (rHuEPO) in this setting is now well established and has had a dramatic impact on the quality of life of patients with renal disease. With the more widespread use of EPO in other clinical conditions and the advent of novel therapeutic approaches, this is an opportune moment to review the physiology and patho-physiology of this fascinating and essential hormone.

The Abbott Cell Dyn 4000 (CD4000) is the first haematology analyser in which fully-automated reticulocyte measurements can be routinely determined by fluorescence as part of the full blood count. This communication reports the first evaluation of this method which was undertaken by three independent reference laboratories in Belgium, Germany and Italy. A total of 695 different samples was entered into the study which was designed to compare CD4000 reticulocyte information (enumeration and qualitative maturational data) with results determined in parallel with the existing manual (supravital staining) reference procedure, and two semi-automated fluorescent assays (Becton Dickinson FACScan and Sysmex R1000 instruments). These studies revealed good agreement between the CD4000 and the manual procedure, with no inter-method bias. Comparison of CD4000 and FACScan reticulocyte measurements, however, indicated a distinct tendency for the FACScan to give higher reticulocyte estimates than the CD4000. Finally, the comparison of the CD4000 with the Sysmex R1000 showed excellent agreement in the range 0-6% reticulocytes, although there was some inter-method bias in the higher range (> 15%). Analysis of agreement levels between the methods using specific 'clinical decision points' confirmed the tendency for overestimation by the FACScan, in that 58% of the samples with a reticulocytopenia of < 0.5% as defined by the CD4000 gave FACScan results within the normal range (0.5-1.8%). In contrast, there was absolute agreement between the CD4000 and the Sysmex R1000 for all reticulocytopenias. Comparison (195 samples) of instrument fluorescent reticulocyte maturation profiles demonstrated an exponential relationship (r = 0.78) between CD4000 IRF and R1000 HFR (highly fluorescent reticulocyte fraction) values. The suggestion that the CD4000 IRF values includes some of the MFR as well the HFR reticulocyte fraction was confirmed as the correlation between the CD4000 IRF and the Sysmex R1000 MFR plus HFR percentages was linear (r = 0.82). This study confirms a high performance level for the CD4000 automated fluorescent reticulocyte method.

Erythropoietin (Epo) was sequentially measured by radioimmunoassay in 11 patients with acute renal failure (ARF) of varied aetiology. Epo rapidly decreased to a level inappropriately low for the haemoglobin, the reduced Epo value persisting throughout the oliguric phase and for up to 2 weeks after the restoration of apparently normal renal function. Epo values found in ARF were: at referral 18.2 +/- 9.5, mid-oliguria 14.4 +/- 6.8, diuresis 15.6 +/- 5.8, and recovery 25.1 +/- 15.8 mU/ml. Results are compared with 34 patients with end-stage chronic renal failure, 42 with non-renal anaemia, and 96 normal subjects. Epo deficiency alone is an inadequate explanation of the rapid reduction in haemoglobin at the onset of ARF, but would appear to be an important factor in the maintenance of anaemia in prolonged ARF and accounts for the slow increase in haemoglobin following recovery.

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We studied the effect of age on the relationship between haemoglobin and serum erythropoietin (EPO) levels in anaemic patients. 568 patients over 70 years of age were compared with 137 patients under 70 and a reference group of 144 patients of all ages with proven iron deficiency. EPO was measured using a radioimmunoassay. We found that elderly patients with a normocytic anaemia (N = 375) had a statistically lower EPO response than younger patients with normocytic anaemia (N = 61) (p < 0.05) or patients of all ages with iron‐deficiency anaemia (p < 0.05). There was no difference between the sexes. Elderly patients with microcytic or macrocytic anaemia had a normal EPO response as compared to the “gold standard” of iron deficiency. These findings suggest that a proportion of elderly patients with normocytic anaemia has an impaired EPO response.