A useful relationship between the presence of extramedullary erythropoeisis and the level of the soluble form of the transferrin receptor in a large cohort of adult patients with thalassemia intermedia: a prospective study

Ricchi, Paolo; Ammirabile, Massimiliano; Costantini, Silvia; Matola, Tiziana Di; Verna, Roberto; Diano, Alvaro; Foglia, M; Spasiano, Anna; Cinque, Patrizia; Prossomariti, Luciano

doi:10.1007/s00277-011-1385-y

Cited by 24 publications

(19 citation statements)

References 19 publications

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“…Previous studies24,25 have demonstrated higher levels of serum sTfR in patients with β-thalassemia syndromes compared with the healthy controls. In accordance with this, the sTFR level was found to be significantly higher in each of TM and TI children compared to the control group.…”

Section: Discussionmentioning

confidence: 81%

Study of Serum Haptoglobin Level and Its Relation to Erythropoietic Activity in Beta Thalassemia Children .

Ragab

Safan

Badr

2015

Mediterr J Hematol Infect Dis

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BackgroundSerum haptoglobin (Hp) is a reliable marker for hemolysis regardless the inflammatory state.ObjectiveWe investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV) infection and iron load in β-thalassemia children.MethodsTwenty two β-thalassemia major (TM),20 β-thalassemia intermedia (TI) children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered. Serum ferritin, Hp and transferrin receptor levels (sTfR) (by ELISA ), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (by colorimetric method) were assayed. Markers of hepatitis C virus (HCV) were done by PCR.ResultsThe mean Hp levels among the studied groups were as follows; 8.02 ± 0.93 (mg/dl), 8.6 ±0.72 (mg/dl) and 122 ± 18.5(mg/dl) for TM, TI and the controls respectively. Both patient groups had significantly lower Hp level compared to the controls (P<0.0001) with significant lower level in TM compared to TI children ( P= 0.034). Significant inverse correlations were found between serum Hp and sTfR levels ( reflecting the erythropoietic activity) in thalassemia children combined and in each group (TM and TI) as well as among HCV infected children. STfR was the only significant independent predictor for serum Hp level (t= −5.585, P<0.0001). Among HCV infected patients, no significant correlation was found between serum Hp and serum transaminases.ConclusionSerum Hp depletion in thalassemia had significant relation to disease severity and correlated well with their erythropoietic activity, as assessed by the measurement of sTfR without significant relation to HCV infection. Extensive multicenter studies are recommended.

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Section: Discussionmentioning

confidence: 81%

Study of Serum Haptoglobin Level and Its Relation to Erythropoietic Activity in Beta Thalassemia Children .

Ragab

Safan

Badr

2015

Mediterr J Hematol Infect Dis

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“…Our data suggest that ineffective erythropoiesis in ␤-thalassemia results from dysfunctional differentiation because of excess iron and unpaired ␣ globin chains and is reversed by exogenous transferrin; this finding is also supported by normalized serum sTfR1, a typical marker reflecting degree of defective or iron-deficient erythropoiesis. 30,31 This newly established method is broadly applicable in the study of altered murine erythropoiesis. Moreover, its use will probalby provide important leads for mechanistic studies defining stage-specific defects in erythroid maturation in inherited and acquired red cell disorders.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of murine terminal erythroid differentiation in vivo: novel method to study normal and disordered erythropoiesis

Liu

Zhang

Ginzburg

et al. 2013

Blood

198

214

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Key Points• The study establishes a reliable method to quantify differentiating mouse erythroblasts and to monitor terminal mouse erythropoiesis in vivo.• Quantitative analysis of erythropoiesis of thalassemia mice revealed stage-specific changes in terminal erythroid differentiation.Terminal erythroid differentiation is the process during which proerythroblasts differentiate to produce enucleated reticulocytes. Although it is well established that during murine erythropoiesis in vivo, 1 proerythroblast undergoes 3 mitosis to generate sequentially 2 basophilic, 4 polychromatic, and 8 orthochromatic erythroblasts, currently there is no method to quantitatively monitor this highly regulated process. Here we outline a method that distinguishes each distinct stage of erythroid differentiation in cells from mouse bone marrow and spleen based on expression levels of TER119, CD44, and cell size. Quantitative analysis revealed that the ratio of proerythroblasts:basophilic: polychromatic:orthromatic erythroblasts follows the expected 1:2:4:8 ratio, reflecting the physiologic progression of terminal erythroid differentiation in normal mice. Moreover, in 2 stress erythropoiesis mouse models, phlebotomy-induced acute anemia and chronic hemolytic anemia because of 4.1R deficiency, the ratio of these erythroblast populations remains the same as that of wild-type bone marrow. In contrast, in anemic ␤-thalassemia intermedia mice, there is altered progression which is restored to normal by transferrin treatment which was previously shown to ameliorate the anemic phenotype. The means to quantitate in vivo murine erythropoiesis using our approach will probably have broad application in the study of altered erythropoiesis in various red cell disorders. (Blood. 2013;121(8):e43-e49)

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“…The strong negative correlation of Hb levels with sTfR (Fig A) supports the concept that sTfR levels reflect erythroid mass, which increases with greater anaemia. Indeed, sTfR levels have been linked with the incidence of extramedullary erythropoiesis in β TI patients (Ricchi et al , ). It is notable that patients with the most previous transfusion episodes (>20) had the lowest Hb values and the highest EPO and sTfR levels, indicative of a group of patients with the greatest demand on the erythron when not regularly transfused.…”

Section: Discussionmentioning

confidence: 99%

Iron overload across the spectrum of non‐transfusion‐dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions

et al. 2016

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SummaryNon‐transfusion‐dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non‐transferrin‐bound iron (NTBI) were elevated and correlated across diagnostic subgroups. NTBI correlated with soluble transferrin receptor (sTfR), labile plasma iron (LPI) and nucleated red blood cells (NRBCs), with elevations generally confined to previously transfused patients. Splenectomised patients had higher NTBI, TfSat, NRBCs and SF relative to LIC, than non‐splenectomised patients. LPI elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (sTfR, growth differentiation factor‐15, NRBCs) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with >20 prior transfusions, and correlated inversely with TfSat, NTBI, LPI and NRBCs. Hepcidin/SF ratios were low, consistent with hepcidin suppression relative to iron overload. Increased NTBI and, by implication, risk of extra‐hepatic iron distribution are more likely in previously transfused, splenectomised and iron‐overloaded NTDT patients with TfSat >70%.

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A useful relationship between the presence of extramedullary erythropoeisis and the level of the soluble form of the transferrin receptor in a large cohort of adult patients with thalassemia intermedia: a prospective study

Cited by 24 publications

References 19 publications

Study of Serum Haptoglobin Level and Its Relation to Erythropoietic Activity in Beta Thalassemia Children .

Study of Serum Haptoglobin Level and Its Relation to Erythropoietic Activity in Beta Thalassemia Children .

Quantitative analysis of murine terminal erythroid differentiation in vivo: novel method to study normal and disordered erythropoiesis

Iron overload across the spectrum of non‐transfusion‐dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions

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