1,721,168 research outputs found
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
Association of α globin gene quadruplication and heterozygous β thalassemia in patients with thalassemia intermedia
No full textTen patients with thalassemia intermedia with variable
severity and apparent simple heterozygosis for b0 39 C>T
nonsense mutation were submitted to clinical, hematologic
and molecular studies. The presence of an unknown
molecular defect (silent b-thalassemia) unlinked to the b
cluster interacting with the heterozygous b thalassemia,
was previously postulated in these families. Analysis of the
a globin gene cluster with PCR-based methods (MLPA,
GAP-PCR, digestion with restriction enzymes) detected
complex rearrangements in the a cluster. A duplication of
the a globin gene locus, including the upstream regulatory
region, was present in all the patients, associated in some
of them with deletion or non-deletion a thalassemia. The
variability of the clinical phenotype correlates with the
degree of the globin chain imbalance. The presence of a
globin cluster duplication should be considered in patients
heterozygote for b-thalassemia with thalassemia intermedia
phenotype and in the carriers of suspected silent b thalassemia.
Key words: thalassemia intermedia, a-globin gene quadruplication,
silent b thalassemia, MLPA.
Citation: Sollaino MC, Paglietti ME, Perseu L, Giagu N, Loi D,
and Galanello R. Association of a globin gene quadruplication
and heterozygous b thalassemia in patients with thalassemia
intermedia. Haematologica 2009.94:1445-1448.
doi: 10.3324/haematol.2009.005728
©2009 Ferrata Storti Foundation. This is an open-access paper
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
Prima e dopo la splenectomia: terapia combinata in un paziente con compromissione cardiaca secondaria all'accumulo di ferro.
No full textPopulation-based genetic screening. Current opinion in Genetics and Development (Review)
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