Serum Erythropoietin Levels in Patients with Beta Thalassemia Major and Intermedia

Nişli, Güngör; Kavaklı, Kaan; Aydınok, Yeşim; Öztop, Senay; Çetingül, Nazan

doi:10.3109/08880019709030902

Cited by 20 publications

(20 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mean value of hematocrit (Hct) in the patients with TM (18.70 ± 3.51%) was lower than those with TI (25.24 ± 4.19%) whereas the mean serum Epo levels were significantly higher in TM than TI patients. Moreover, it was found that an inverse correlation between the serum values of Epo and Hct was observed in both TI and TM patients 42,43 . In addition, these data were explained as serum Epo levels increased in all thalassemia patients, despite repeated transfusion.…”

Section: Discussionmentioning

confidence: 89%

“…In addition, these data were explained as serum Epo levels increased in all thalassemia patients, despite repeated transfusion. This is explained by the fact that multiple transfusions may modulate the response of serum Epo to the degree of anemia, resulting in increased Epo levels and independent anemia in the TM patients 42,43 . In addition, the mean serum level of Epo was found to be higher in the thalassemic patients than in the controls, but transfused subjects had lower pretransfusional serum concentrations of Epo than untransfused ones 44 .…”

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Evaluation of angiogenesis with vascular endothelial growth factor in patients with thalassemia major

Olgar¹,

Kara²,

Hicyilmaz

et al. 2010

Pediatrics International

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 97%

Evaluation of angiogenesis with vascular endothelial growth factor in patients with thalassemia major

Olgar¹,

Kara²,

Hicyilmaz

et al. 2010

Pediatrics International

View full text Add to dashboard Cite

show abstract

“…Increased erythropoiesis in β‐thalassaemia/Hb E patients has been proposed to occur as compensation for the anaemic condition resulting from the loss of erythroid cells (Olivieri, 1999) as a consequence of ineffective erythropoiesis (Mathias et al , 2000). The anaemic state is believed to result in increased production of EPO, which drives the increased erythropoiesis, and increased levels of circulating EPO in thalassaemic patients have been reported in several studies (Nisli et al , 1997; Chaisiripoomkere et al , 1999; Paritpokee et al , 2002) and are consistent with the levels found in the patients in this study, which showed a 3‐ to 60‐fold elevation of EPO levels, with no observable relationship between EPO levels and either total haemoglobin or haemoglobin F levels (data not shown). As such, the central belief, that increased EPO (either directly or in synergy with other cytokines) results in increased erythropoiesis, in thalassaemic patients, remains largely unsupported and untested.…”

Section: Discussionmentioning

confidence: 99%

Increased erythropoiesis of β‐thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation

Wannatung¹,

Lithanatudom²,

Leecharoenkiat³

et al. 2009

Br J Haematol

View full text Add to dashboard Cite

Increased erythropoiesis of b-thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activationThe thalassaemias are a group of disorders characterized by the under production of globin chains as a consequence of a wide range of underlying genetic abnormalities (Weatherall & Clegg, 2001). The a and b chains of haemoglobin A are the most commonly affected genes and both a-and b-thalassaemias represent a worldwide clinical problem (Weatherall & Clegg, 2001). The underproduction of one chain leads to a resultant excess of the other chain in the red cell that is toxic to the cell and leads to a reduced red cell life span, increased haemolysis and ineffective erythropoiesis, which is believed to arise through accelerated cell death by apoptosis of the immature erythroid cell (Yuan et al, 1993), either as a direct or indirect consequence of the unpaired globin chain deposition within the cell (Mathias et al, 2000). In b-thalassaemia apoptosis is believed to occur primarily at the polychromatophilic normoblast stage (Mathias et al, 2000). The combination of ineffective erythropoiesis, increased haemolysis and reduced life span of the mature red cell lead to the anaemic condition, which stimulates the production of erythropoietin (EPO) leading to erythroid hyperplasia in the bone marrow (Chen et al, 1992;Centis et al, 2000;Mathias et al, 2000;Pootrakul et al, 2000;Kittikalayawong et al, 2005;Mai et al, 2007) and markedly increased levels of circulating EPO have been documented in thalassaemic patients (Nisli et al, 1997;Chaisiripoomkere et al, 1999;Paritpokee et al, 2002). However, despite the increase in erythroid precursors, the overall response to the anaemia is limited due to the ineffective erythropoiesis leading to the accelerated death of immature erythroid cells. In severe cases of Summary b-thalassaemia is one of the most common inherited anaemias, arising from a partial or complete loss of b-globin chain synthesis. In severe cases, marked bone marrow erythroid hyperplasia, believed to result from erythropoietin (EPO)-mediated feedback from the anaemic condition is common, however, as yet, no study has investigated EPO-mediated signal transduction in thalassaemic erythroid cells. Using proerythroblasts generated from peripheral blood circulating CD34 + haematopoietic progenitor cells, the activation of the mitogen-activated protein kinase/extracellular signalregulated kinases (MAPK/ERKs) pathway was examined under conditions of steady state growth, cytokine deprivation and post-EPO stimulation. Levels of cellular cyclic adenosine monophosphate (cAMP) and Ca 2+ were determined as was the degree of erythroid expansion. A significantly higher basal level of phosphorylation of ERK1/2 was observed in b-thalassaemia/Hb E proerythroblasts as compared to normal controls, which was coupled with significantly higher levels of both cAMP and Ca 2+ . Modulation of either cAMP or Ca 2+ or direct inhibition of MAPK/ERK kinase (MEK) reduced basal levels of ERK1/2 phosphorylation, as well as significantly...

show abstract

“…In thalassaemic patients, several reports suggest that serum Epo values are variable and do not correlate closely with the degree of anaemia. Some authors have demonstrated that serum Epo levels in thalassaemic patients do not show consistent correlation with clinical measures of erythropoietic activity (Camaschella et al ., 1996; Nisli et al ., 1997). In our reference group, an inverse correlation was observed between Hb/Epo in β‐thalassaemic patients, indicating adequate Epo production for the degree of anaemia.…”

Section: Discussionmentioning

confidence: 99%

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

Roque¹,

Sandoval²,

Aggio³

2001

Clinical &Amp; Laboratory Haematology

View full text Add to dashboard Cite

Serum erythropoietin (Epo) and soluble transferrin receptor (sTR) were measured in a locally defined reference population (n=100): healthy volunteers (n=50); iron- deficiency anaemia (n=41) and haemolytic anaemia (n=9) (beta-thalassaemia, n = 4; autoimmune, n=5). Our data demonstrated an inverse relationship between erythroid activity and Epo levels. The regression line between Ln Epo and haemoglobin (Hb) was highly significant: P < 0.0001, r2=0.8275, Ln Epo=8.5346-0.04275 Hb, confidence limit 95%. The mean observed/predicted (O/P) ratio of Ln (Epo) was 1.01 +/- 0.11. We demonstrated that the serum Epo concentration in this particular population correlated consistently with clinical measures of erythropoietic activity. sTR, a new index of erythropoiesis, varied from 16.1 to 148 nmol/l, mean 62.0 nmol/l in the anaemic patients' group. The relationship between Ln Epo and Ln sTR was highly significant: P < 0.0001. We conclude that locally defined regression analyses are crucial for correct data interpretation and can indicate whether or not Epo production is appropriate or inappropriate. Serial determinations of sTR could help in the assessment of response to therapeutic doses of Epo.

show abstract

Serum Erythropoietin Levels in Patients with Beta Thalassemia Major and Intermedia

Cited by 20 publications

References 5 publications

Evaluation of angiogenesis with vascular endothelial growth factor in patients with thalassemia major

Evaluation of angiogenesis with vascular endothelial growth factor in patients with thalassemia major

Increased erythropoiesis of β‐thalassaemia/Hb E proerythroblasts is mediated by high basal levels of ERK1/2 activation

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

Contact Info

Product

Resources

About