Quantitative assessment of erythropoiesis and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin

Abstract

We evaluated the quantitative value of a simple model of erythropoiesis, based on the basic assumptions that the red blood cell (RBC) mass determines erythropoietin (Epo) production, which in turn stimulates erythropoietic activity. The RBC mass was quantitated by direct isotopic measurement (RCM), Epo production by serum Epo levels, and erythropoiesis by the ferrokinetic measurement of the erythron transferrin uptake (ETU), the serum transferrin receptor (TfR) level, and the reticulocyte (retic) index, and was completed by an evaluation of overall marrow erythron cellularity. We studied a total of 195 subjects, including 31 normal individuals, 38 patients with polycythemia, and 126 patients with various forms of anemia. Instead of only quantitating Epo and erythropoiesis in absolute terms, we also evaluated them in relation to the degree of anemia or polycythemia, and expressed the results as a ratio of observed values to values predicted from the regression equations between hematocrit (Hct) on the one hand, and Epo, TfR, and ETU on the other, obtained in a carefully selected subpopulation. The slope of the regression of TfR (as well as ETU) versus Hct was very similar to the slope of the regression of Epo versus Hct. Average EPO and TfR (as well as ETU) values predicted from the regression equations were quite comparable to observed values in most groups of subjects, with exceptions predictable from knowledge of the pathophysiology of these hematologic disorders. We identified four major patterns of erythropoiesis, ie, normal, hyperdestruction (with variants of hemolysis or ineffective erythropoiesis), intrinsic marrow hypoproliferation, and defective Epo production. Dissecting out groups of patients showed much greater heterogeneity than when patients were analyzed by group. This was particularly true in the case of a hypoproliferative component being combined with hyperdestruction, giving what we called a “mixed disorder of erythropoiesis.” We conclude that the pathophysiology of anemia can be assessed by a simple measurement of Hct, retic index, Epo, and TfR levels, with Epo and TfR being more informative when expressed in relation to the degree of anemia. The model is particularly useful for detecting the presence of multiple mechanisms of anemia in the same patient. However, it has limitations inherent to the relative invalidity of TfR in iron deficiency, the imprecision of a retic count, and the difficulty in distinguishing hemolysis from ineffective erythropoiesis in some patients and in recognizing a component of hyperdestruction in hypoproliferative anemia.

In vitro culture growth of erythroid progenitors and serum erythropoietin assay in the differential diagnosis of polycythaemia

“…Several investigators have measured the serum EPO concentrations in patients with polycythaemia [23][24][25][26][27][28][29][30][31][32][33][34]; however, the results are conflicting because of differences ᮊ 1998 Blackwell Science Ltd, European Journal of Clinical Investigation, 28, 569-576 in the sensitivity and specificity of the assay systems used. Using a sensitive radioimmunoassay, we found that pretreatment serum EPO levels in PV patients were not different from those in PE-PV patients, but were significantly lower than those in normal control subjects and other polycythaemia groups.…”

Serum erythropoietin and its relation with soluble transferrin receptor in patients with different types of anaemia in a locally defined reference population

“…The predicted value was de®ned by a regression equation of Epo vs. Hb in reference subjects. The O/P ratio is below 1 if the observed value is lower than the predicted one; in reference subjects, the 95% con®dence interval ranged from 0.80 to 1.22 (Beguin et al, 1993).…”

Prognostic significance of endogenous erythropoietin in long‐term outcome of patients with acute decompensated heart failure

“…We used a similar approach to those used in previous studies to determine the response of endogenous EPO to the haemoglobin level in anaemic patients. 10,15,16 To avoid interference with EPO production or EPO activity due to renal function and HF, a sample of 35 anaemic patients in our outpatient clinic cohort (different from our ADHF cohort) without renal disease or HF (previous history of HF, symptoms or signs of HF, LVEF <50%, or moderate to severe valvular…”