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

Severe forms of anemia in children in the developing countries may be characterized by different clinical manifestations at particular stages of development. Whether this reflects developmental changes in adaptation to anemia or other mechanisms is not clear. The pattern of adaptation to anemia has been assessed in 110 individuals with hemoglobin (Hb) E beta-thalassemia, one of the commonest forms of inherited anemia in Asia. It has been found that age and Hb levels are independent variables with respect to erythropoietin response and that there is a decline in the latter at a similar degree of anemia during development. To determine whether this finding is applicable to anemia due to other causes, a similar study has been carried out on 279 children with severe anemia due to Plasmodium falciparum malaria; the results were similar to those in the patients with thalassemia. These observations may have important implications both for the better understanding of the pathophysiology of profound anemia in early life and for its more logical and cost-effective management.
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PMID:Age-related changes in adaptation to severe anemia in childhood in developing countries. 1751 43

A patient with thalassemia minor and idiopathic scoliosis was scheduled for posterior vertebral arthrodesis. The diagnosis of thalassemia minor was made during the preoperative assessment. Preoperative blood cell count displayed the following data: red blood count 5.4 x 106/microL, haemoglobin 11.6 g/dL and hematocrit 36.9%. As corrective surgery for scoliosis is associated with major blood loss, the patient was scheduled for preoperative treatment with human recombinant erythropoietin (rHuEPO), autologous blood donation, intraoperative blood cell salvage and administration of tranexamic acid. The use of rHuEPO was intended to increase hemoglobin (12.1 g/dL) levels at the moment of surgery following the donation of 2 autologous blood units. 1000 mL of salvaged blood were processed. The output line of the blood cell salvage machine did not show any sign of increased red cell haemolysis. The postoperative course was uneventful and the patient was discharged from the postoperative intensive care unit on day 7 after surgery with no allogenic blood transfusion. No references detailing the use of rHuEPO and autologous blood donation preoperatively in patients with thalassemia minor and only one case report discussed the utility of intraoperative blood cell salvage in a patient with thalassemia intermedia. Although further experience is needed, this case report suggests that even for patients with thalassemia minor, methods focused on allogenic blood salvage can be used safely.
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PMID:Bloodless surgery in a patient with thalassemia minor. Usefulness of erythropoietin, preoperative blood donation and intraoperative blood salvage. 1752 23

The present study found that the cyclic adenosine monophosphate (cAMP)-dependent pathway efficiently induced gamma-globin expression in adult erythroblasts, and this pathway plays a role in gamma-globin gene (HBG) expression in beta-thalassaemia. Expression of HBG mRNA increased to about 46% of non-HBA mRNA in adult erythroblasts treated with forskolin, while a cyclic guanosine monophosphate (cGMP) analogue induced HBG mRNA to levels <20% of non-HBA mRNA. In patients with beta-thalassaemia intermedia, cAMP levels were elevated in both red blood cells and nucleated erythroblasts but no consistent elevation was found with cGMP levels. The transcription factor cAMP response element binding protein (CREB) was phosphorylated in nucleated erythroblasts and its phosphorylation levels correlated with HBG mRNA levels of the patients. Other signalling molecules, such as mitogen-activated protein kinases and signal transducers and activators of transcription proteins, were phosphorylated at variable levels and showed no correlations with the HBG mRNA levels. Plasma levels of cytokines, such as erythropoietin, stem cell factor and transforming growth factor-beta were increased in patients, and these cytokines induced both HBG mRNA expression and CREB phosphorylation. These results demonstrate that the cAMP-dependent pathway, the activity of which is augmented by multiple cytokines, plays a role in regulating HBG expression in beta-thalassaemia.
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PMID:Expression of the gamma-globin gene is sustained by the cAMP-dependent pathway in beta-thalassaemia. 1761 26

In thalassemia, deficient globin-chain production during erythropoiesis results in anemia. Thalassemia may be further complicated by iron overload (frequently exacerbated by blood transfusion), which induces numerous endocrine diseases, hepatic cirrhosis, cardiac failure and even death. Accumulation of iron in the absence of blood transfusions may result from inappropriate suppression of the iron-regulating peptide hepcidin by an erythropoietic mechanism. To test this hypothesis, we examined erythroblast transcriptome profiles from 15 healthy, nonthalassemic donors. Growth differentiation factor 15 (GDF15), a member of the transforming growth factor-beta superfamily, showed increased expression and secretion during erythroblast maturation. Healthy volunteers had mean GDF15 serum concentrations of 450 +/- 50 pg/ml. In comparison, individuals with beta-thalassemia syndromes had elevated GDF15 serum levels (mean 66,000 +/- 9,600 pg/ml; range 4,800-248,000 pg/ml; P < 0.05) that were positively correlated with the levels of soluble transferrin receptor, erythropoietin and ferritin. Serum from thalassemia patients suppressed hepcidin mRNA expression in primary human hepatocytes, and depletion of GDF15 reversed hepcidin suppression. These results suggest that GDF15 overexpression arising from an expanded erythroid compartment contributes to iron overload in thalassemia syndromes by inhibiting hepcidin expression.
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PMID:High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. 1782 18

CD177 (PRV1) expression is strongly related to polycythaemia vera (PV). Whilst studying CD177 expression in PV patients and controls, individuals with beta-thalassaemia minor were found to display an elevated expression of CD177. The study was expanded to include patients with thalassaemia intermedia, sickle cell/beta-thalassaemia and thalassaemia major. CD177 expression was increased in these thalassaemic groups and correlated with their erythropoietic activity, as assessed by the measurement of serum erythropoietin and soluble transferrin receptor levels. Within this context, elevated CD177 expression is not only a specific feature of PV but may be an indicator of increased erythropoietic activity in thalassaemia syndromes.
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PMID:Increased CD177 (PRV1) expression in thalassaemia and the underlying erythropoietic activity. 1832 72

Erythroblastic islands, the specialized niches in which erythroid precursors proliferate, differentiate, and enucleate, were first described 50 years ago by analysis of transmission electron micrographs of bone marrow. These hematopoietic subcompartments are composed of erythroblasts surrounding a central macrophage. A hiatus of several decades followed, during which the importance of erythroblastic islands remained unrecognized as erythroid progenitors were shown to possess an autonomous differentiation program with a capacity to complete terminal differentiation in vitro in the presence of erythropoietin but without macrophages. However, as the extent of proliferation, differentiation, and enucleation efficiency documented in vivo could not be recapitulated in vitro, a resurgence of interest in erythroid niches has emerged. We now have an increased molecular understanding of processes operating within erythroid niches, including cell-cell and cell-extracellular matrix adhesion, positive and negative regulatory feedback, and central macrophage function. These features of erythroblast islands represent important contributors to normal erythroid development, as well as altered erythropoiesis found in such diverse diseases as anemia of inflammation and chronic disease, myelodysplasia, thalassemia, and malarial anemia. Coupling of historical, current, and future insights will be essential to understand the tightly regulated production of red cells both in steady state and stress erythropoiesis.
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PMID:Erythroblastic islands: niches for erythropoiesis. 1865 Apr 62

Eryptosis, the suicidal death of erythrocytes, is characterised by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are recognised by macrophages, which engulf and degrade the affected cells. Reported triggers of eryptosis include osmotic shock, oxidative stress, energy depletion, ceramide, prostaglandin E(2), platelet activating factor, hemolysin, listeriolysin, paclitaxel, chlorpromazine, cyclosporine, methylglyoxal, amyloid peptides, anandamide, Bay-5884, curcumin, valinomycin, aluminium, mercury, lead and copper. Diseases associated with accelerated eryptosis include sepsis, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency, hemolytic uremic syndrome and Wilsons disease. Eryptosis may be inhibited by erythropoietin, adenosine, catecholamines, nitric oxide (NO) and activation of G-kinase. Most triggers of eryptosis except oxidative stress are effective without activation of caspases. Their signalling involves formation of prostaglandin E(2) with subsequent activation of cation channels and Ca2+ entry and/or release of platelet activating factor (PAF) with subsequent activation of sphingomyelinase and formation of ceramide. Ca2+ and ceramide stimulate scrambling of the cell membrane. Ca2+ further activates Ca2+-sensitive K+ channels leading to cellular KCl loss and cell shrinkage and stimulates the protease calpain resulting in degradation of the cytoskeleton. Eryptosis allows defective erythrocytes to escape hemolysis. On the other hand, excessive eryptosis favours the development of anemia. Thus, a delicate balance between proeryptotic and antieryptotic mechanisms is required to maintain an adequate number of circulating erythrocytes and yet avoid noneryptotic death of injured erythrocytes.
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PMID:Erythrocyte programmed cell death. 1872 Apr 18

Extramedullary haematopoiesis (EH) is the production of blood cell precursors outside the bone marrow that occurs in various disorders, such as thalassaemia, sickle cell anaemia, hereditary spherocytosis, polycythaemia vera, myelofibrosis and other haematological diseases. In chronic anaemia, it is a physiological response to increased erythropoietin. In some other conditions, such as myeloid metaplasia, polycythaemia vera or chronic myeloid leukaemia, EH is due to a clonal disorder of haematopoiesis that enables progenitor cells to escape from the marrow and lodge in other organs. EH usually involves the liver, spleen and lymph nodes or it can be paravertebral, intrathoracic, pelvic. It is often asymptomatic but can sometimes lead to symptomatic tumour-like masses. Treatment options are still controversial and limited, including hypertransfusion regimen, surgical treatment, radiotherapy and hydroxyurea (HU). We describe intrathoracic and symptomatic pelvic EH masses in a 48-year-old woman and intrathoracic bilateral masses causing respiratory insufficiency with pleural effusion in a 42-year-old male, both affected by thalassaemia intermedia. Both patients showed a clinical improvement with hydroxyurea therapy and occasional blood transfusions.
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PMID:Effect of hydroxyurea on extramedullary haematopoiesis in thalassaemia intermedia: case reports and literature review. 1904 18

Multisubunit complexes containing molecular chaperones regulate protein production, stability, and degradation in virtually every cell type. We are beginning to recognize how generalized and tissue-specific chaperones regulate specialized aspects of erythropoiesis. For example, chaperones intersect with erythropoietin signaling pathways to protect erythroid precursors against apoptosis. Molecular chaperones also participate in hemoglobin synthesis, both directly and indirectly. Current knowledge in these areas only scratches the surface of what is to be learned. Improved understanding of how molecular chaperones regulate erythropoietic development and hemoglobin homeostasis should identify biochemical pathways amenable to pharmacologic manipulation in a variety of red blood cell disorders including thalassemia and other anemias associated with hemoglobin instability.
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PMID:Chaperoning erythropoiesis. 1910 56

The percentage of hypochromic red cells (%Hypo) is a diagnostic tool that has been used with biochemical markers to diagnose iron disturbances and is incorporated to National Kidney Foundation KDOQI guidelines for monitoring recombinant human erythropoietin therapy. %Hypo measurement has been restricted to analysers manufactured by Siemens. Low haemoglobin density (LHD%), a new parameter provided by Beckman-Coulter, is derived from the traditional mean cell haemoglobin concentration (MCHC), using the mathematical sigmoid transformation [see equation in text]. This study aimed to establish LHD% values in the normal population and in different types of anaemia, to investigate its clinical usefulness in the study of iron status and its correlation with %Hypo. Samples from 449 patients [120 healthy individuals, 86 iron deficiency anaemia (IDA), 102 chronic kidney disease, 58 anaemia of chronic disease and 83 beta-thalassaemia carriers] were run sequentially on the LH 750 (Beckman-Coulter) and Advia 2120 (Siemens) analysers. The reliability of LHD% as a marker of iron deficiency was evaluated on a group of 152 consecutive patients with IDA. Good correlation was observed between %Hypo and LHD%, r(2) = 0.869. Receiver operating characteristic curve analysis for LHD% and the diagnosis of iron deficiency was: cut-off point 4.0%; area under the curve 0.976; sensitivity 95.2%; specificity 93.3%. There was a good level of agreement between LHD% and %Hypo. Both are suitable parameters for determining iron status and its availability for erythropoiesis, with the same clinical significance.
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PMID:The new mature red cell parameter, low haemoglobin density of the Beckman-Coulter LH750: clinical utility in the diagnosis of iron deficiency. 1922 May 25


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