|
|
Previous Article | Table of Contents | Next Article 
Quantitative assessment of erythropoiesis and functional classification of
anemia based on measurements of serum transferrin receptor and
erythropoietin
Y Beguin, GK Clemons, P Pootrakul and G Fillet
Department of Hematology, University of Liege, Belgium.
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.
Volume 81,
Issue 4,
pp. 1067-1076,
02/15/1993
Copyright © 1993 by The American Society of Hematology

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
G. Bergamaschi, K. Markopoulos, R. Albertini, A. Di Sabatino, F. Biagi, R. Ciccocioppo, E. Arbustini, and G. R. Corazza
Anemia of chronic disease and defective erythropoietin production in patients with celiac disease
Haematologica,
December 1, 2008;
93(12):
1785 - 1791.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Brookhart, S. Schneeweiss, J. Avorn, B. D. Bradbury, K. J. Rothman, M. Fischer, J. Mehta, and W. C. Winkelmayer
The Effect of Altitude on Dosing and Response to Erythropoietin in ESRD
J. Am. Soc. Nephrol.,
July 1, 2008;
19(7):
1389 - 1395.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. van der Meer, D. J. Lok, J. L. Januzzi, P. W. B.-A. de la Porte, E. Lipsic, J. van Wijngaarden, A. A. Voors, W. H. van Gilst, and D. J. van Veldhuisen
Adequacy of endogenous erythropoietin levels and mortality in anaemic heart failure patients
Eur. Heart J.,
June 2, 2008;
29(12):
1510 - 1515.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Theurl, M. Theurl, M. Seifert, S. Mair, M. Nairz, H. Rumpold, H. Zoller, R. Bellmann-Weiler, H. Niederegger, H. Talasz, et al.
Autocrine formation of hepcidin induces iron retention in human monocytes
Blood,
February 15, 2008;
111(4):
2392 - 2399.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. A Northrop-Clewes
Interpreting indicators of iron status during an acute phase response - lessons from malaria and human immunodeficiency virus
Ann Clin Biochem,
January 1, 2008;
45(1):
18 - 32.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Artunc and T. Risler
Serum erythropoietin concentrations and responses to anaemia in patients with or without chronic kidney disease
Nephrol. Dial. Transplant.,
October 1, 2007;
22(10):
2900 - 2908.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. S. Walsh and E.-E.-D. Saleh
Anaemia during critical illness
Br. J. Anaesth.,
September 1, 2006;
97(3):
278 - 291.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Haiden, K. Klebermass, F. Cardona, J. Schwindt, A. Berger, C. Kohlhauser-Vollmuth, B. Jilma, and A. Pollak
A Randomized, Controlled Trial of the Effects of Adding Vitamin B12 and Folate to Erythropoietin for the Treatment of Anemia of Prematurity
Pediatrics,
July 1, 2006;
118(1):
180 - 188.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Theurl, V. Mattle, M. Seifert, M. Mariani, C. Marth, and G. Weiss
Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease
Blood,
May 15, 2006;
107(10):
4142 - 4148.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Opasich, M. Cazzola, L. Scelsi, S. De Feo, E. Bosimini, R. Lagioia, O. Febo, R. Ferrari, A. Fucili, R. Moratti, et al.
Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure
Eur. Heart J.,
November 1, 2005;
26(21):
2232 - 2237.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Weiss and L. T. Goodnough
Anemia of Chronic Disease
N. Engl. J. Med.,
March 10, 2005;
352(10):
1011 - 1023.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K.-H. Chang, M. Tam, and M. M. Stevenson
Inappropriately low reticulocytosis in severe malarial anemia correlates with suppression in the development of late erythroid precursors
Blood,
May 15, 2004;
103(10):
3727 - 3735.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Baron, P. Frere, G. Fillet, and Y. Beguin
Recombinant Human Erythropoietin Therapy Is Very Effective after an Autologous Peripheral Blood Stem Cell Transplant When Started Soon after Engraftment
Clin. Cancer Res.,
November 15, 2003;
9(15):
5566 - 5572.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Verhoef, C. E. West, R. Kraaijenhagen, S. M. Nzyuko, R. King, M. M. Mbandi, S. van Laatum, R. Hogervorst, C. Schep, and F. J. Kok
Malarial anemia leads to adequately increased erythropoiesis in asymptomatic Kenyan children
Blood,
November 15, 2002;
100(10):
3489 - 3494.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Brugnara
A Hematologic "Gold Standard" for Iron-deficient States?
Clin. Chem.,
July 1, 2002;
48(7):
981 - 982.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. J. Lee, E.-J. Oh, Y.-J. Park, H. K. Lee, and B. K. Kim
Soluble Transferrin Receptor (sTfR), Ferritin, and sTfR/Log Ferritin Index in Anemic Patients with Nonhematologic Malignancy and Chronic Inflammation
Clin. Chem.,
July 1, 2002;
48(7):
1118 - 1121.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Verhoef, C. E West, P. Ndeto, J. Burema, Y. Beguin, and F. J Kok
Serum transferrin receptor concentration indicates increased erythropoiesis in Kenyan children with asymptomatic malaria
Am. J. Clinical Nutrition,
December 1, 2001;
74(6):
767 - 775.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
M. Piron, M. Loo, A. Gothot, F. Tassin, G. Fillet, and Y. Beguin
Cessation of intensive treatment with recombinant human erythropoietin is followed by secondary anemia
Blood,
January 15, 2001;
97(2):
442 - 448.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Chatterjee, U. E. Nydegger, and P. Mohacsi
Serum erythropoietin in heart failure patients treated with ACE-inhibitors or AT1 antagonists
Eur J Heart Fail,
December 1, 2000;
2(4):
393 - 398.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Reich, C. Buhrer, G. Henze, D. Ohlendorf, M. Mesche, P. Sinha, A. Kage, C. Muller, B. Vetter, and A. E. Kulozik
Oral isobutyramide reduces transfusion requirements in some patients with homozygous beta -thalassemia
Blood,
November 15, 2000;
96(10):
3357 - 3363.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. J. Stoltzfus, H. M. Chwaya, A. Montresor, M. Albonico, L. Savioli, and J. M. Tielsch
Malaria, Hookworms and Recent Fever Are Related to Anemia and Iron Status Indicators in 0- to 5-y Old Zanzibari Children and These Relationships Change with Age
J. Nutr.,
July 1, 2000;
130(7):
1724 - 1733.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
M. Voulgarelis, S. I G Kokori, J. P A Ioannidis, A. G Tzioufas, D. Kyriaki, and H. M Moutsopoulos
Anaemia in systemic lupus erythematosus: aetiological profile and the role of erythropoietin
Ann Rheum Dis,
March 1, 2000;
59(3):
217 - 222.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
A. C. Looker, M. Loyevsky, and V. R. Gordeuk
Increased Serum Transferrin Saturation Is Associated with Lower Serum Transferrin Receptor Concentration
Clin. Chem.,
December 1, 1999;
45(12):
2191 - 2199.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Loo and Y. Beguin
The Effect of Recombinant Human Erythropoietin on Platelet Counts Is Strongly Modulated by the Adequacy of Iron Supply
Blood,
May 15, 1999;
93(10):
3286 - 3293.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Corazza, Y. Beguin, P. Bergmann, M. Andre, A. Ferster, C. Devalck, P. Fondu, M. Buyse, and E. Sariban
Anemia in Children With Cancer Is Associated With Decreased Erythropoietic Activity and Not With Inadequate Erythropoietin Production
Blood,
September 1, 1998;
92(5):
1793 - 1798.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Hellstrom-Lindberg, T. Ahlgren, Y. Beguin, M. Carlsson, J. Carneskog, I. M. Dahl, I. Dybedal, G. Grimfors, L. Kanter-Lewensohn, O. Linder, et al.
Treatment of Anemia in Myelodysplastic Syndromes With Granulocyte Colony-Stimulating Factor Plus Erythropoietin: Results From a Randomized Phase II Study and Long-Term Follow-Up of 71 Patients
Blood,
July 1, 1998;
92(1):
68 - 75.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Cazzola, R. Guarnone, P. Cerani, E. Centenara, A. Rovati, and Y. Beguin
Red Blood Cell Precursor Mass as an Independent Determinant of Serum Erythropoietin Level
Blood,
March 15, 1998;
91(6):
2139 - 2145.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. E. Mast, M. A. Blinder, A. M. Gronowski, C. Chumley, and M. G. Scott
Clinical utility of the soluble transferrin receptor and comparison with serum ferritin in several populations
Clin. Chem.,
January 1, 1998;
44(1):
45 - 51.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Cazzola, G. Bergamaschi, L. Tonon, E. Arbustini, M. Grasso, E. Vercesi, G. Barosi, P. E. Bianchi, G. Cairo, and P. Arosio
Hereditary Hyperferritinemia-Cataract Syndrome: Relationship Between Phenotypes and Specific Mutations in the Iron-Responsive Element of Ferritin Light-Chain mRNA
Blood,
July 15, 1997;
90(2):
814 - 821.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Cazzola, F. Mercuriali, and C. Brugnara
Use of Recombinant Human Erythropoietin Outside the Setting of Uremia
Blood,
June 15, 1997;
89(12):
4248 - 4267.
[Full Text]
[PDF]
|
 |
|
|
|