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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The correction of anemia in patients with chronic renal failure (CRF) has become the most important application of recombinant human erythropoietin (rHuEpo). The merits of rHuEpo therapy in patients with CRF are overt. Firstly, patients with CRF have an absolute deficiency in endogenous erythropoietin production and a relatively low maintenance dose of rHuEpo (often less than 100 IU/kg body weight per week) is effective in avoiding regular transfusions in the majority of the patients with CRF. Secondly, rHuEpo is able to avoid long-term complications of frequent transfusions (hemochromatosis, transfusion-transmissible diseases). Thirdly, patients with uremia notice a considerable improvement in quality of life (QOL) after initiation of rHuEpo. These advantages justify administration of this costly drug in CRF patients. The use of rHuEpo outside the setting of uremia do, however, not cover the complete spectrum of beneficial effects as compared to its use in (pre)dialysis patients. The aim of this overview is to provide some annotations on recently approved (cisplatin-induced anemia, preoperative anemia, zidovudine-related anemia) and possibly future (several types of malignancy and inflammation) indications for rHuEpo in non-uremic patients, leaving out the correction of anemia due to relatively uncommon disorders in the Dutch population (such as sickle cell anemia and thalassemia).
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PMID:Erythropoietin treatment for non-uremic patients: a personal view. 1004 90

We describe the four most common groups of neonatal anemia and their treatments, with particular emphasis on erythropoietin therapy. The hemolytic anemias include the ABO incompatibility (much more frequent, nowadays, than the Rh incompatibility, which has nearly disappeared following the use of anti-D immunoglobulin in postpartum Rh-negative mothers), hereditary spherocytosis and G-6-PD deficiency. Among hypoplastic anemias, that caused by Parvovirus B19 predominates, by far, over Diamond-Blackfan anemia, alpha-thalassemia and the rare sideroblastic anemias. "Hemorrhagic" anemias occur during twin-to-twin transfusions, or during feto-maternal transfusions. Finally, the multifactorial anemia of prematurity develops principally as a result of the rapid expansion of the blood volume in this group of patients. Erythropoietin therapy, often at doses much higher than those used in the adult, should be seriously considered in most cases of non-hypoplastic neonatal anemias, to minimise maximally the use of transfusions.
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PMID:[Common anemias in neonatology]. 1006 73

Of the uncommon anemias, "common" types include the anemia of renal disease, thalassemia, myelodysplastic syndrome and the anemia of chronic disease. These conditions may be suggested by the clinical presentation, laboratory test values and peripheral blood smear, or by failure of the anemia to respond to iron supplements or nutrient replacement. The principal cause of the anemia of renal disease is a decreased production of red blood cells related to a relative deficiency of erythropoietin. When treatment is required, erythropoietin is administered, often with iron supplementation. In the anemia of chronic disease, impaired iron transport decreases red blood cell production. Treatment is predominantly directed at the underlying condition. Since iron stores are usually normal, iron administration is not beneficial. Thalassemia minor results from a congenital abnormality of hemoglobin synthesis. The disorder may masquerade as mild iron deficiency anemia, but iron therapy and transfusions are often not indicated. In the myelodysplastic syndrome, blood cell components fail to mature, and the condition may progress to acute nonlymphocytic leukemia. The rate of progression depends on the subtype of myelodysplasia, but the leukemia is usually resistant to therapy.
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PMID:'Common' uncommon anemias. 1006 9

The goal of the present study was to analyze if sustained delivery of elevated doses of recombinant erythropoietin (Epo), by genetically modified and immunoprotected allogenic cells, was able to correct the chronic anemia, characteristic of a spontaneous mouse model of beta-thalassemia (Hbb thal 1). Mouse C2C12 myoblast cells were transfected with a plasmid containing the mouse Epo cDNA and a mutated dihydrofolate reductase (DHFR) gene for gene amplification upon administration of increasing doses of methotrexate. In order to immunoprotect the transplanted cells, the stably modified cells were loaded into polyethersulfone microporus hollow fibers which were implanted subcutaneously into Hbb thal 1 mice. An increase in hematocrit starting 2 weeks after implantation was associated with elevated blood levels of Epo and an improved red blood cell phenotype. The latter indicated an improvement of cell morphology and membrane defects, in particular a reduced amount of free alpha hemoglobin chain, the hallmark of globin chain imbalance in beta-thalassemia. A reduction of reticulocyte count contrasting with the increase in hematocrit was also observed suggesting an improved erythrocyte survival. We conclude that the phenotype can be durably improved in some beta-thalassemic mice upon in vivo delivery of recombinant Epo by polymer encapsulated cells. Sustained elevated delivery of recombinant Epo holds promise for the treatment of beta-thalassemia-associated chronic anemia.
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PMID:Improvement of mouse beta-thalassemia upon erythropoietin delivery by encapsulated myoblasts. 1043 99

SV40-based vectors are very efficient in gene delivery into human hematopoietic cells. In the present work, we investigated the expression of constructs carrying the human beta-globin gene that were delivered as beta-globin pseudovirions. Expression studies were performed by RNA analysis of primary human erythroid progenitors cultivated from peripheral blood of beta(0)-thalassemia patients who are unable to produce normal beta-globin RNA. This erythroid culture system recapitulates in vitro the process of growth, differentiation, and maturation of authentic erythroid precursors. The progenitors were induced to differentiate by the addition of erythropoietin (EPO). Five days later, the cells were infected with pseudovirions containing the normal beta-globin gene, and RNA was harvested on day 8. The results showed significant levels of normal beta-globin gene mRNA. A small DNA fragment derived from the 5'-region of the HSII element of the human beta-globin locus control region (LCR) enhanced expression of the linked beta-globin gene 20-30-fold. Normal beta-globin mRNA expression was in direct correlation to the multiplicity of infection. These studies suggest the potential feasibility of using the beta-globin delivery system for gene therapy of beta-thalassemia.
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PMID:Expression of beta-globin in primary erythroid progenitors of beta-thalassemia patients using an SV40-based gene delivery system. 1064 62

Thalassemia is the world's most common hereditary disease, and is a paradigm of monogenic genetic diseases. Because of increased population mobility, the disease is found today throughout the world, even in places far from the tropical areas in which it arose. Therapy of thalassemia has in the past been confined to transfusion and chelation. Recently, novel modes of therapy have been developed for thalassemia, based on the pathophysiology and molecular pathology of the disease, both of which have been extensively studied. This review will discuss the therapeutic modalities currently in use for the supportive treatment of thalassemia, both those that are standard therapy and those that are in clinical trials. We will include transfusion, chelation (intravenous and oral), antioxidants and various inducers of fetal hemoglobin (hydroxyurea, erythropoietin, butyrates, hemin). Most of the newer therapies are suitable primarily for thalassemia intermedia patients. In addition, the treatment modalities currently in use for the curative treatment of thalassemia major will be discussed, including bone marrow transplantation in its various forms. Experimental therapeutic methods, such as intrauterine bone marrow transplantation and gene therapy, are included. Physicians caring for thalassemia patients have an increasing variety of treatment options available. Future clinical studies will determine the place of newer agents and modalities in improving the quality of life as well as the life expectancy of thalassemia patients.
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PMID:New trends in the treatment of beta-thalassemia. 1073 72

beta-Thalassemias are highly prevalent genetic disorders that can cause severe hemolytic anemia. The main pathophysiologic feature of beta-thalassemia is the accumulation of unpaired alpha-globin chains in erythrocyte precursors and red blood cells (RBCs). This accumulation alters cell membrane function and results in early cell destruction and ineffective erythropoiesis. Correction of globin chain imbalance through the induction of fetal hemoglobin (HbF) synthesis is a tentative therapeutic approach for this class of diseases. In short-term in vitro or in vivo assays, recombinant human erythropoietin increases the frequency of erythroid precursors programmed to HbF in humans and to beta-minor globin in mice. In contrast, long-term treatment of beta-thalassemic patients did not induce HbF significantly. We took advantage of highly efficient adeno-associated virus-mediated (AAV-mediated) gene transfer into mouse muscle to induce a robust and sustained secretion of mouse erythropoietin in beta-thalassemic mice, which represent a suitable model for human beta-thalassemia intermedia. A 1-year follow-up of 12 treated animals showed a stable correction of anemia associated with improved RBC morphology, increased beta-minor globin synthesis, and decreased amounts of alpha-globin chains bound to erythrocyte membranes. More effective erythropoiesis probably accounted for a reduction of erythroid cell proliferation, as shown by decreased proportions of circulating reticulocytes and by reduced iron 59 ((59)Fe) incorporation into erythroid tissues. This study indicates that the continuous delivery of high amounts of autologous erythropoietin induced a sustained stimulation of beta-minor globin synthesis and a stable improvement of erythropoiesis in the beta-thalassemic mouse model. (Blood. 2000;95:2793-2798)
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PMID:Improvement of erythropoiesis in beta-thalassemic mice by continuous erythropoietin delivery from muscle. 1077 23

The anemia of pregnancy in presence of beta-thalassemia intermedia usually aggravates pregnancy procedure. In the present study we investigated whether the administration of recombinant human erythropoietin (rHuEpo) recombinant human erythropoietin in combination with iron and folic acid may ameliorate blood indices as an alternative choice to blood transfusion.
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PMID:Effective treatment of beta-thalassemia intermedia during pregnancy with rHuEpo. A case report. 1085 61

Serum erythropoietin (EPO) levels were determined by enzyme linked immunosorbent assay (ELISA) in 61 thalassemic patients, consisting of 23 thalassemia major (TM) patients with multiple transfusion, 38 patients with thalassemia intermedia (TI). Thirty-two normal controls were also studied. The mean serum EPO levels were significantly higher in both groups with TM (165.96 +/- 17.31 mlU/ml) and TI (126.43 +/- 50.56 mlU/ml) compared with the control group (8.33 +/- 3.91 mlU/ml). 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 level were significantly higher in TM than TI patients. An inverse correlation between the serum values of EPO and Hct was observed in both TI and TM patients, however this correlation was significant only in TI (r = -0.61, p<0.001). These data showed that serum EPO levels increased in all thalassemia patients despite repeated transfusion. Multiple transfusion may modulate the response of serum EPO to the degree of anemia, resulting in increased EPO levels and independent anemia in the TM patients.
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PMID:Serum erythropoietin levels in thalassemia major and intermedia. 1092 78

Effective management of early anaemia in the course of chronic renal insufficiency requires the following: (i) implementing an efficient diagnostic strategy to exclude common contributing factors; (ii) initiating epoetin therapy for the majority of patients; for and (iii) ensuring adequate iron supply erythropoiesis. Diagnostic inquiry is warranted whenever the haemoglobin concentration is below the normal range adjusted for age and gender. The most efficient diagnostic approach is to assume erythropoietin deficiency, exclude iron deficiency, and pursue further diagnostic tests only when red-cell indices are abnormal or when leukopenia or thrombocytopenia are also present. Macrocytosis should prompt an inquiry into alcoholism, B12 deficiency, or folate deficiency. Microcytosis suggests iron deficiency or thalassaemia. Associated cytopenias raise the possibility of alcohol toxicity, pernicious anaemia, malignancy, or myelodysplastic syndrome. Epoetin therapy is warranted whenever the haemoglobin concentration has fallen below 10.0 g/dl. To initiate therapy prior to dialysis, epoetin should be administered at an average dose of 100 IU/kg/week (80-120 IU/kg/week, 50-150 IU/kg/ week) by subcutaneous injection. Haemoglobin concentration should be monitored every 2 weeks and the epoetin dose adjusted by increments or decrements of 25% to maintain a rate of rise of haemoglobin concentration of 0.2-0.6 g/dl (0.3 0.6 g/dl/week, 0.2-0.5 g/dl/week). When the target range is achieved, the dose of epoetin should be continually adjusted to maintain a stable haemoglobin concentration. Transferrin saturation and ferritin concentration should be monitored monthly, and sufficient iron provided to maintain transferrin saturation above 20%. The lower the haemoglobin concentration, the greater the likelihood that future intravenous iron will be required. Oral iron supplements should be avoided, since they are costly, ineffective, and troublesome to patients. Finally, a blunted therapeutic response to epoetin therapy provides important diagnostic information and gnostic inquiry.
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PMID:Management of early renal anaemia: diagnostic work-up, iron therapy, epoetin therapy. 1103 56


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