1,721,072 research outputs found
Nuovi farmaci ferrochelanti e nuove strategie di ferro chelazione nella talassemia major
No full textNei 5 anni considerati in questa ricerca bibliografica (Gennaio 2005-Dicembre 2009) sono emersi articoli di grande rilevanza per quanto riguarda la terapia ferrochelante nella talassemia. Se 10 anni fa, infatti, il primo farmaco ferrochelante orale, il deferiprone, ha affiancato la desferrioxamina nel trattamento del sovraccarico di ferro, negli ultimi 5 anni si è assistito allo sviluppo di un nuovo ferrochelante orale, il deferasirox, in commercio in Italia dal 2007 e alla diffusione della terapia di associazione sequenziale e combinata di desferrioxamina e deferiprone. L’introduzione di metodi non invasivi per la misurazione dell’accumulo di ferro nel fegato, negli organi endocrini e soprattutto nel cuore, sono alla base di studi osservazionali, prospettici e randomizzati che hanno
valutato l’efficacia dei ferrochelanti, in monoterapia e in combinazione nel ridurre il sovraccarico d’organo le complicanze secondarie all’accumulo marziale e nel prolungare la sopravvivenza. La disponibilità di diversi farmaci ha modificato la strategia ferrochelante anche nei bambini. È emerso che l’età, l’apporto trasfusionale, il grado e la sede dell’accumulo di ferro, le complicanze già presenti, la risposta alla terapia e la compliance sono oggi le variabili da considerare nell’individuare la terapia ferrochelante migliore, personalizzata e “ritagliata” sul singolo paziente.In the last five years (January 2005-December 2009), very relevant original studies have been published on iron chelation therapy in thalassemia major. Three chelators are now available, desferrioxamine, the first oral iron chelator deferiprone, and deferasirox, recently licensed in many countries. The most important studies recently published have evaluated the efficacy of the chelators as monotherapy and in combination in terms of reduction of iron overload in different organs, improvement of complications, and survival. It appears that the management of transfusion dependent thalassemia has been revolutionized by the availability of accurate and non-invasive methods for assessing iron load in the heart and liver and by the option of tailoring chelation according to the degree of iron load, medical history, patient’s age, transfusional regimen, compliance and responsiveness to treatment
β-Thalassemia
No full textβ-Thalassemia is caused by reduced (β +) or absent (β 0) synthesis of the β-globin chains of hemoglobin. Three clinical and hematological conditions of increasing severity are recognized: the β-thalassemia carrier state, thalassemia intermedia, and thalassemia major, a severe transfusion-dependent anemia. The severity of disease expression is related mainly to the degree of α-globin chain excess, which precipitates in the red blood cell precursors, causing both mechanic and oxidative damage (ineffective erythropoiesis). Any mechanism that reduces the number of unbound α-globin chains in the red cells may ameliorate the detrimental effects of excess α-globin chains. Factors include the inheritance of mild/silent β-thalassemia mutations, the coinheritance of α-thalassemia alleles, and increased Î 3-globin chain production. The clinical severity of β-thalassemia syndromes is also influenced by genetic factors unlinked to globin genes as well as environmental conditions and management. Transfusions and oral iron chelation therapy have dramatically improved the quality of life for patients with thalassemia major. Previously a rapidly fatal disease in early childhood, β-thalassemia is now a chronic disease with a greater life expectancy. At present, the only definitive cure is bone marrow transplantation. Therapies undergoing investigation are modulators of erythropoiesis and stem cell gene therapy
Pathophysiology of beta thalassaemia
No full textIn beta thalassemia, unbalanced alpha globin chain synthesis results in severely rheologically compromised erythrocytes with premature destruction in the peripheral circulation and ineffective erythropoiesis within the bone marrow and in extramedullary sites. In nontransfused beta thalassemia patients, erythropoiesis,anemia and hypoxia down-regulate hepcidin, the master regulator of iron homeostasis. Hepcidin deficiency in turn allows excessive duodenal iron absorption and development of systemic iron overload. In regularly transfused patients iron overload is mostly due to red cell breakdown. When the iron binding capacity of transferrin is saturated, iron can appear in the serum in a free form, called Non-Transferrin-Bound Iron, a powerful catalyst for the formation of free radicals, capable of causing oxidative stress and damage to mitochondria, lysosomes, lipid membranes, proteins, and DNA. Apart from the iron overload-related complications, other pathological conditions such as bone disease, gallstones and thromboembolic events occur in a relevant proportion of subjects with thalassemia
Once-daily oral deferasirox for the treatment of transfusional iron overload
No full textThe increasing use of blood transfusions, combined with extended patient survival, has led to an increase in the number of patients at risk of developing transfusional iron overload. Clinical data have shown that the once-daily oral iron chelator deferasirox is effective in adults and children with various transfusion-dependent anemias, including β-thalassemia and the myelodysplastic syndromes. Deferasirox has a defined, clinically manageable safety profile. The most common treatment-related adverse events are mild gastrointestinal disorders, skin rash and mild, nonprogressive serum creatinine increases. The deferasirox clinical trial program is continuing in Phase II/III extension phases and Phase IV trials. Long-term data continue to support the efficacy and safety of deferasirox. Convenient, effective and tolerable chelation therapy with deferasirox is a significant development in the treatment of transfusional iron overload
Beta-thalassemia
Full text linkAbstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta globin gene on chromosome 11, leading to reduced (beta+) or absent (beta0) synthesis of the beta chains of hemoglobin (Hb). Transmission is autosomal recessive; however, dominant mutations have also been reported. Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Differential diagnosis is usually straightforward but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemia). Genetic counseling is recommended and prenatal diagnosis may be offered. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. In some circumstances, spleen removal may be required. Bone marrow transplantation remains the only definitive cure currently available. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Prognosis for individuals with beta-thalassemia has improved substantially in the last 20 years following recent medical advances in transfusion, iron chelation and bone marrow transplantation therapy. However, cardiac disease remains the main cause of death in patients with iron overload.</p
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