Erythropoietin production and erythropoiesis in compensated and anaemic states of hereditary spherocytosis.
A compensated haemolytic state is defined by decreased red cell life-span without anaemia, i.e. by increased erythropoiesis in the absence of the physiological stimulus for erythropoietin (Epo) production. We evaluated s-Epo levels and the expansion of erythropoiesis (as measured by circulating transferrin receptor, s-TfR) in 32 patients with hereditary spherocytosis (HS) with the aim of verifying whether the enhanced erythropoiesis of compensated haemolysis was Epo-dependent. 20 of the patients (62.5%) had normal Hb values (> 12 g/dl in females and > 13 g/dl in males). Their compensated haemolytic state was the result of up to 8.2 times normal s-Epo and up to 3.9 times normal s-TfR levels, which were maintained by physiological regulation of erythropoiesis, as documented by the inverse dependence of Hb on s-Epo levels. Considering that patients with iron-deficiency anaemia represented the predicted physiological Epo response to anaemia, the observed/predicted in s-Epo ratio (O/P ratio) was calculated in HS patients with anaemia and was used as an index of the adequateness of Epo production. All the anaemic HS patients had an O/P ratio > 1, documenting inappropriately high s-Epo levels. This work demonstrates that the compensated haemolytic state of HS patients is produced by an inappropriately high s-Epo level, and that the pattern of Epo overproduction is a biological characteristic of the disease.
Guarnone
R
R
Istituto di Medicina Interna e Oncologia Medica, IRCCS Policlinico S. Matteo, Pavia, Italy.
Centenara
E
E
Zappa
M
M
Zanella
A
A
Barosi
G
G
D000293:Adolescent; D000328:Adult; D018798:Anemia, Iron-Deficiency / Q000097:blood; D002648:Child; D004920:Erythropoiesis; D004921:Erythropoietin / Q000096:biosynthesis* / Q000097:blood; D005260:Female; D006461:Hemolysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000032:analysis; D012016:Reference Values; D013103:Spherocytosis, Hereditary / Q000097:blood*
D011990:Receptors, Transferrin; D004921:Erythropoietin