Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Erythropoietin levels were determined in 50 Greek females: 20 beta-thalassaemia (beta-thal) heterozygotes, 15 with a diagnosis of iron-deficiency anaemia and 15 normal controls. In beta-thal trait carriers, the erythropoietin levels were slightly higher than in normal controls (16.65 +/- 4.43 vs. 12.84 +/- 2.47 mU/ml); these levels were significantly lower than those in iron-deficient subjects with the same degree of anaemia (55.24 +/- 31.35 mU/ml). In both groups, the erythropoietin levels are statistically correlated with the severity of anaemia (r = -0.537 p < 0.05 for iron deficiency; r = -0.610 p < 0.01 for beta-thal heterozygotes). In beta-thal heterozygotes, a close inverse correlation with red cell number and erythropoietin levels was also noted. It is suggested that microcytosis accompanying beta-thal trait constitutes an additional factor intervening in the regulation of erythropoiesis.
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PMID:Erythropoietin levels and microcytosis in heterozygous beta-thalassaemia. 935 45

Although the current treatment of thalassemia with regular transfusions and assiduous chelation leads to a good quality of life and long survival, it is cumbersome and expensive. Various treatments have recently been explored. Bone marrow transplantation can cure thalassemia, but there was severe mortality in initial trials. It is safely successful only in patients in good clinical condition and with a compatible donor. Certain drugs, including azacytidine, butyrate, hydroxyurea, and erythropoietin may increase the production of fetal hemoglobin; their practical value is being explored. New potential oral iron chelators are under investigation. L1, the best evaluated, appears effective, but its potential toxicity remains undefined.
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PMID:Recent advances in the management of thalassemia. 937 87

Augmentation of gamma-gene synthesis by using recombinant human erythropoietin (r-Hu-EPO) represents a new approach to the therapy of beta-thalassemia. A prospective study was conducted in 26 transfusion-dependent beta-thalassemia major patients. r-Hu-EPO (Eprex/Cilag, Switzerland) was given to the patients at an initial dose of 500 IU/kg s.c. 3 times a week for at least 2 months during which no transfusion was applied. A sustained hemoglobin (Hb) level greater than 8 g/dl was considered as a response to EPO treatment. In the patients whose Hb levels remained under 8 g/dl or did not increase in comparison to pretreatment levels within 4 weeks, the dose of r-Hu-EPO was increased to 1,000 IU/kg 3 times a week and applied for another 4 weeks. Only 16 cases also received oral iron supplementation. The whole blood and reticulocyte counts, the biochemical tests including BUN, creatinine, AST, ALT, alkaline phosphatase and ferritin were done and the percentages of HbF and F cells were analyzed regularly. At the end of the 2nd month, 6 cases qualified to continue with the trial. At the end of the 6th month, r-Hu-EPO therapy was ceased in 3 cases of the 6 since their Hb levels had decreased below 7 g/dl. Only 3 cases (11.5%) continued with the r-Hu-EPO therapy without transfusion for up to 12 months. In conclusion, r-Hu-EPO may be useful in some selected transfusion-dependent patients with beta-thalassemia major. Selection criteria should include a mild beta-genotype of coinheritance of alpha-thalassemia, splenectomy and pretreatment reticulocyte response of the patients as well as the patients' compliance.
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PMID:Recombinant erythropoietin trial in children with transfusion-dependent homozygous beta-thalassemia. 940 97

Serum erythropoietin (sEpo) concentration is primarily related to the rate of renal production and, under the stimulus of hypoxia, increases exponentially as hemoglobin (Hb) decreases. Additional factors, however, appear to influence sEpo, and in this work, we performed studies to evaluate the role of the red blood cell precursor mass. We first compared the relationship of sEpo with Hb in patients with low versus high erythroid activity. The first group included 27 patients with erythroid aplasia or hypoplasia having serum transferrin receptor (sTfR) levels < 3 mg/L (erythroid activity < 0.6 times normal), while the second one included 28 patients with beta-thalassemia intermedia having sTfR levels > 10 mg/L (erythroid activity > 2 times normal). There was no difference between the two groups with respect to Hb (8.3 +/- 1.6 v 8.0 +/- 1.3 g/dL, P > .05), but sEpo levels were notably higher in patients with low erythroid activity (1,601 +/- 1,542 v 235 +/- 143 mU/mL, P < . 001). In fact, multivariate analysis of variance (ANOVA) showed that, at any given Hb level, sEpo was higher in patients with low erythroid activity (P < .0001). Twenty patients undergoing allogeneic or autologous bone marrow transplantation (BMT) were then investigated. A marked increase in sEpo was seen in all cases at the time of marrow aplasia, disproportionately high when compared with the small decrease in Hb level. Sequential studies were also performed in five patients with iron deficiency anemia undergoing intravenous (IV) iron therapy. Within 24 to 72 hours after starting iron treatment, marked decreases in sEpo (up to one log magnitude) were found before any change in Hb level. Similar observations were made in patients with megaloblastic anemia and in a case of pure red blood cell aplasia. These findings point to an inverse relationship between red blood cell precursor mass and sEpo: at any given Hb level, the higher the number of red blood cell precursors, the lower the sEpo concentration. The most likely explanation for this is that sEpo levels are regulated not only by the rate of renal production, but also by the rate of utilization by erythroid cells.
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PMID:Red blood cell precursor mass as an independent determinant of serum erythropoietin level. 949 Jul 1

Thalassemia is an inherited hematological disorder which can generally be classified according to the affected globin imbalance (alpha- or beta-globin) into two main types, i.e. alpha-thalassemia and beta-thalassemia, respectively. There is a wide range of cellular abnormalities associated with thalassemic erythrocytes such as hypochromia, microcytosis, reduced cellular deformability and membrane oxidative damage. The red cell abnormalities lead to premature destruction with marrow erythroid hyperplasia and ineffective erythropoiesis. The abnormalities in thalassemic red blood cells have been found along the erythroid differentiation pathway other than the mature stage as previously shown in bone marrow erythroid precursors and in reticulocytes, the penultimate stage of erythroid differentiation. However, there is a lag in our understanding of the more primitive erythroid stages due to the difficult and hazardous marrow aspiration and heterogeneity of cells derived. We have utilized a novel method of Two-Phase Liquid Culture (TPLC) of beta-thalassemia/HbE erythroid precursors instead of conventional semisolid culture. This type of liquid culture can given higher cell yield with quite synchronous cell differentiation stages and easily be applied for other cellular analytical techniques. The peripheral blood mononuclear cells (PBMC) obtained from non-splenectomized and splenectomized beta-thalassemia/HbE patients were first cultured in medium supplemented with 5637 conditioned medium for a 6-day period (phase I) and then transferred to medium supplemented with recombinant human erythropoietin to allow the terminal differentiation of erythroid precursors (phase II). During the phase I or II, the cultured cells were periodically sampled to determine the cell number, cytocentrifuged on glass slides and stained with Wright stain for morphological assessment of their differentiation stages and analyzed flow cytometrically by staining with fluoresceinated anti-transferrin receptor (anti-CD71) and R-phycoerythrin-conjugated anti-glycophorin A. After assessment by flow cytometry, the remaining stained cells were cytocentrifuged on glass slides and photographed by a fluorescent microscope and a laser scanning confocal microscope. The results of morphological assessment, flow cytometric analysis and microscopic pictures will be presented.
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PMID:An in vitro study on thalassemic erythroid precursors in liquid culture. 964 Jun 5

Thalassemia is one of the most common genetic disorders in Thailand. The thalassemic patients have many pathophysiologic changes secondary to chronic anemia. During these last few years there have been many trials to cure or improve the anemic condition in thalassemia by using various agents, including erythropoietin (EPO). Thus it is very important to understand the EPO response to different degree of anemia in the thalassemic patients. In this study we evaluated the EPO status in 53 beta-thalassemia/HbE patients, from 4-61 years old, by enzyme-linked immunosorbent assay. The results showed that the levels of EPO in beta-thalassemia/HbE patients were much higher than in normal control subjects: mean +/- SE = 527 +/- 183.20 and 3.45 +/- 0.47 mIU/ml respectively. The reverse correlation between the levels of EPO and hematocrit (r = -0.704) was also observed. There was also a tendency to have higher levels of EPO in beta-thal/HbE children than in adults, although this was statistically insignificant. The observed versus predicted levels of EPO (log O/P ratio) showed that most patients had good EPO response to the degree of anemia. However, inappropriate decrease of EPO response was observed in 8/40 adult patients. The EPO levels in these patients were not correlated with any physical or laboratory studies, including kidney function. We thus propose that if EPO is to be considered as one of the alternative treatment to the thalassemic patients, in the future, it may benefit only the patients with low EPO levels.
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PMID:Difference in pattern of erythropoietin response between beta-thalassemia/hemoglobin E children and adults. 964 Jun 15

Homozygous beta thalassemia affects thousands of people around the world. Current management of this condition includes regular transfusion of red cells, which leads to transfusional iron overload requiring chelation therapy: increasing hemoglobin levels while decreasing or eliminating iron overload is therefore a major therapeutic goal in the treatment of thalassemia. Bone marrow transplantation may achieve this goal, but it is not an option for most patients. This study reports on efforts to increase gamma-globin transcription and HbF production using sodium phenylbutyrate (SPB) and hydroxyurea (HU). It was found that 36% (4/11) of all patients or 50% (4/8) of non-transfused patients responded to SPB (increase in Hb levels of 1 g/dL). A positive correlation between baseline serum erythropoietin level and likelihood of response to SPB was observed. Since HU may also increase HbF production, evaluation of combination therapy with these drugs is underway and preliminary results are reported.
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PMID:Hemoglobin switching protocols in thalassemia. Experience with sodium phenylbutyrate and hydroxyurea. 966 30

The clinical effectiveness of Hydroxyurea in thalassemia is still controversial. The present paper puts together the authors' experience in two groups of patients with thalassemia intermedia and sickle cell/beta-thalassemia treated with varying dosages of hydroxyurea over several months. A third group received hydroxyurea along with recombinant human erythropoietin. Our observations are summarized in that treatment with hydroxyrea results in a significant increase of fetal hemoglobin with no change of the total hemoglobin levels. The drug causes also a considerable increase of the erythrocyte volume and hemoglobin content while the MCHC values remain unchanged. As a rule, and without objective criteria so far, patients state feeling better and having more energy. The authors postulate that this feeling may reflect the significant decrease of ineffective erythropoiesis resulting by the replacement of the poorly hemoglobinized, prematurely dying erythroid progenitor and red cell population by another population of cells with higher hemoglobin content and longer survival, the regeneration of which requires less energy and consumption. As expected, patients with sickle cell/beta-thalassemia have also fewer crises and painful episodes. The above findings are in keeping with the few available reports in the literature.
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PMID:Hydroxyurea therapy in thalassemia. 966 34

The rationale for treatment with recombinant human erythropoietin (rHuEPO) in thalassemia came from studies in baboons, thalassemic mice and in erythroid cultures. The results demonstrated an increase in gamma globin synthesis and consequently in fetal Hb (Hb F) resulting in improvement in erythropoietic parameters. In addition, endogenous serum Epo levels in various forms of thalassemia were inconsistent and not related to the severity of the anemia. Therefore, several preliminary studies with rHuEPO were performed, mainly on patients with beta thalassemia intermedia. The results indicate: a) a significant, dose-related (500 u/kg to 1000 u/kg x 3/week) increase in thalassemia erythropoiesis without changes in % of Hb F, MCV and MCH, mainly in splenectomized patients; b) the minimum effective dose is 500 u/kg x 3/week; c) there were no major side effects during the continuous treatment period of 9 months. In order to improve both quantitative and qualitative thalassemia erythropoiesis, several trials were undertaken combining rHuEPO with hydroxyurea (HU), which is known to increase % Hb F, MCV and MCH without a major effect on Hb levels. The designed trial included 3 to 6 months of HU alone (20 mg/kg x 4/week), or with rHuEPO alone (500 u/kg x 3/week or 375 u/kg x 2/week) or a combination of the two drugs. The results show an additive effect of the two drugs, in some of the patients. It is not known whether the addition of oral iron to rHuEPO is warranted for maximal erythropoietic response. The major limiting factor in designing large scale clinical trials is the relatively high cost of the drug. Nevertheless rHuEPO alone or in combination with other Hb F modulating drugs may have a positive effect in thalassemia with resulting improvement in the quality of life.
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PMID:The role of recombinant human erythropoietin in the treatment of thalassemia. 966 35

In the management of patients requiring chronic transfusion, various parameters may be used to evaluate the degree of erythroid marrow suppression. The aim of our study was to assess which of these parameters provide the most useful assessment of erythropoiesis. We studied 27 chronically transfused patients, 19 with sickle cell disease (SS patients) and 8 with thalassemia. Thirty-one nonchronically transfused SS patients and 74 healthy children served as controls. We measured serum transferrin receptor levels, reticulocyte counts, hemoglobin (Hb) concentrations and erythropoietin levels. The serum transferrin receptor levels were very elevated in control SS patients and remained significantly elevated in those on transfusion therapy, but were normal in thalassemia patients, indicating a more complete suppression of erythropoiesis. The reticulocyte counts were elevated in all SS patients, even when on chronic transfusion, but were in the normal range in patients with thalassemia. Erythropoietin levels were elevated in patients with thalassemia and in all the SS patients. Hb levels negatively correlated with serum transferrin receptor and erythropoietin in all SS patients. In the transfused SS patients, a higher HbS level correlated with higher reticulocyte counts, transferrin receptor, and erythropoietin levels. In thalassemia patients, erythropoiesis was more completely suppressed, as reflected both by normal reticulocyte counts and near-normal transferrin receptor levels. Though the reticulocyte counts were not significantly different in the transfused SS patients, the serum transferrin receptor levels were less elevated than in SS patients not on transfusion. The serum transferrin receptor level appears to be the most useful marker of marrow erythropoietic activity in chronically transfused SS patients. We recommend that reticulocyte counts be integrated with periodic measurements of serum transferrin receptor levels.
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PMID:Serum transferrin receptor as a marker of erythropoiesis suppression in patients on chronic transfusion. 992 3


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