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

Iron overload is frequently present in patients with thalassemia intermedia, and it becomes evident mainly after the second and third decades of life. The degree of the iron load is heterogeneous ranging from mild to severe. In this study we evaluated the iron status of 38 adult patients with thalassemia intermedia and we looked for factors possibly related to the observed heterogeneity of the iron status. The levels of transferrin saturation (TS), serum ferritin (SF) and desferrioxamine-induced urinary iron excretion (DFU) were spread in a wide range from normal to markedly increased. These indices did not correlate with other parameters such as age, hemoglobin levels and entity of the erythropoietic status. A significant difference in the degree of iron overload was observed between patients who underwent splenectomy and non-splenectomized patients. TS, SF and DFU were significantly higher in splenectomized than in non- splenectomized patients, indicating that the spleen could have a role in the regulation of iron metabolism in these patients.
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PMID:Iron metabolism in thalassemia intermedia. 208 86

Daily subcutaneous infusion of deferoxamine in thalassemia and other transfusion dependent-patients can successfully treat iron overload, but most patients, mainly young children and teenagers may not comply with this method. Experience with nightly intravenous infusion of deferoxamine (8 g) through a subcutaneous-port over 5 out of 21 days, is reported in 4 children with dramatic improvement in clinical status, ferritin levels and quality of life.
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PMID:[Intravenous administration of deferoxamine in over-night hospitalization: efficacy and good psychological tolerance in thalassemic children]. 217 25

Adequate iron chelation in thalassaemia has resulted in a striking improvement in survival, with a reduction of cardiac mortality at age 15 years from 14-3%, and a predicted survival at age 36 years of 85%. Long term desferrioxamine (DF) therapy in thalassaemic children should be started between 2-4 years of age. In addition to daily 8-12 h subcutaneous infusions, intermittent high dose (9-16 g) i.v. supplementation over 24-48 h may be given on the occasion of blood transfusions. In established myocardiopathy continuous i.v. DF infusion at 100-125 mg/kg/d may result in improved myocardial function. In addition, there is considerable current interest in the use of DF in conditions unrelated to iron overload by preventing the formation of free-radicals in inflammatory reactions, or by S-phase inhibition of cell proliferation. Although at present highly experimental, this novel approach may have important implications for the management of patients with inflammatory conditions and perhaps in the control of protozoal infections. Over the last decade several hundred candidate compounds have been studied in cell cultures and in animal models and a number of orally effective iron chelators have been identified, all of which are superior to DF in their in vivo iron chelating effect. Although we do not yet have a new drug which is immediately available for replacing DF in clinical practice, significant progress has already been made, and some of the most promising candidate drugs are currently undergoing extensive toxicity tests in anticipation of their development for large-scale clinical use.
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PMID:Iron chelation. 218 44

This paper describes the status of iron stores, the incidence and the hematological characteristics of iron deficiency anemia in children heterozygous for beta-thalassemia. In beta-thalassemia heterozygotes, iron stores were similar to the controls in infancy and tended to increase with age, reaching levels of moderate iron overload solely in adult males. Iron deficiency anemia occurred less frequently in children heterozygous for beta-thalassemia as compared to normal controls, while no difference between the two groups was observed in the incidence of iron deficiency. Ineffective erythropoiesis, typical of heterozygous beta-thalassemia, by causing an increase of iron absorption may limit the effect of iron shortage. At similar levels of iron depletion, however, children heterozygous for beta-thalassemia develop a more severe anemia as compared to non beta-thalassemic children. With the exception of two children, HbA2 levels in the presence of iron deficiency anemia remain in the range of heterozygous beta-thalassemia. In conclusion, our results indicate that children heterozygous for beta-thalassemia have normal iron stores but are relatively protected against the development of iron deficiency. When iron deficiency anemia develops, its clinical expression is usually more severe than in non beta-thalassemic children.
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PMID:Iron stores and iron deficiency anemia in children heterozygous for beta-thalassemia. 227 77

Disorders of hemoglobin synthesis affect the musculoskeletal system by either causing replacement of bone by hematopoietic tissue, precipitating bone and soft tissue ischemia and necrosis, or a combination of both processes. Less frequently, joints are involved by synovial ischemia, synovial deposition of iron, or microfracture of subchondral bone. Osteopenia is a significant problem in both thalassemia and sickle cell anemia and may result in vertebral and long bone fractures. Growth disturbances are frequently seen but are not often appreciated until adolescence because of improved hematologic management. The cause of the growth problems is multifactorial and may be related to hormonal deficiencies, iron overload, hypoxia, or local trauma to the growth plate secondary to significant osteopenia.
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PMID:Musculoskeletal problems in hemoglobinopathy. 229 57

The histological features of thalassemic bone are imperfectly known, and the roles of bone marrow hyperactivity, iron overload or vitamin D deficiency in the pathogenesis of the disease are not clearly identified. In this study we examined iliac crest biopsies from 17 transfusion-dependent children with homozygous beta-thalassemia and severe radiological skeletal thalassemic changes, including widening of medullary spaces and osteoporosis. Rachitic lesions were not observed. Serum ferritin concentrations were increased in all but one subject. Iron deposits were histochemically detected in bone marrow, at the marrow-bone interface, along cement lines and mineralizing perimeters. Minor changes were present in trabecular bone, and osteomalacia was absent. By contrast, cortical bone exhibited severe changes including fissures and focal mineralization defects. Plasma 25-hydroxyvitamin D (25(OH)D) concentrations measured during the winter (December-May, 6.5 +/- 4.9 ng/ml, mean +/- SD, n = 6) and during the summer (June-November, 13.8 +/- 8.4 ng/ml, n = 9) did not differ from those of age-matched children living in the same country. Seven patients had moderate hypocalcemia but no biological signs suggestive of vitamin D deficiency: all had normal alkaline phosphatase activity, normal or slightly elevated plasma phosphate, only two had low plasma 25(OH)D concentrations and two others supranormal values of plasma immunoreactive parathyroid hormone. These results show that iron overload and vitamin D deficiency do not seem to play an important role in the pathogenesis of thalassemic bone disease, which is characterized by cortical lesions probably related to marrow hyperactivity.
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PMID:Bone disease in children with homozygous beta-thalassemia. 230 56

Four female patients with thalassemia intermedia developed secondary acetabular protrusion. These cases could be the first reported cases of nontraumatic acetabular protrusion in patients with thalassemia. The rarified pelvic bone may be due to medullary hyperplasia, iron overload, or disordered calcium metabolism in conjunction with osteomalacia. The fact that currently patients with beta-thalassemia have a longer life expectancy may explain the recent observation of this entity, which should become more familiar to orthopedic surgeons who treat thalassemia patients in the future.
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PMID:Acetabular protrusion in thalassemia. A report of four cases. 232 31

A standard magnetic resonance imaging (MRI) system allowing spin echo times of 10 ms was used to quantitate liver iron concentration in nine healthy normal subjects and 13 patients with various grades of iron overload. Body iron status was estimated by measuring the serum ferritin concentration. In 11 subjects (two normal healthy controls, eight patients with HLA-related hereditary haemochromatosis and one patient with thalassaemia major) non-haem hepatic iron concentration was determined chemically in biopsy specimens (dry weight), in parallel to serum ferritin and MRI-T2 relaxation times. A moderate correlation (r = 0.79) was obtained for the correlation of the T2-relaxation rate (1/T2) and serum ferritin of the 22 subjects investigated. A much closer correlation (r = 0.98) was observed for the 1/T2 liver iron relationship in the 10 subjects analysed by liver biopsy. It is concluded from these preliminary observations, that MR-imaging may provide a useful non-invasive tool for the quantitative determination of liver iron in iron overload-syndromes.
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PMID:Non-invasive quantitation of liver iron-overload by magnetic resonance imaging. 233 43

The consequences of transfusional iron overload on left ventricular diastolic filling have never been investigated systematically in patients with thalassemia major. In the present study, the pattern of left ventricular filling was assessed by Doppler echocardiography in 32 patients with thalassemia major (age, 17 +/- 5 years) who had not experienced symptoms of heart failure and had normal left ventricular systolic function. Data were compared with those obtained in 32 age-matched and sex-matched normal subjects. An abnormal Doppler pattern of left ventricular filling with increased flow velocity at mitral valve opening followed by an abrupt and premature decrease of flow velocity in early diastole was identified in the patients with thalassemia. Peak flow velocity in early diastole was increased in patients compared with controls (90 +/- 10 vs. 81 +/- 15 cm/sec; p less than 0.01), and rate of deceleration of flow velocity after the early diastolic peak and the ratio between the early and late (atrial) peaks of flow velocity were also increased (1,050 +/- 325 vs. 762 +/- 193 cm/sec2 and 2.7 +/- 0.7 vs. 2.2 +/- 0.5, respectively; p less than 0.001), whereas flow velocity deceleration time was reduced (97 +/- 22 vs. 119 +/- 19 msec; p less than 0.001). This Doppler pattern of diastolic filling is usually described as "restrictive" and reflects a decrease in left ventricular chamber compliance. A restrictive pattern of left ventricular filling was also identified in the subgroup of 16 study patients who had undergone optimal iron chelation therapy with deferoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Restrictive diastolic abnormalities identified by Doppler echocardiography in patients with thalassemia major. 236 28

There has been much progress in basic studies of the beta-thalassemia disorders in recent years, as well as in the practical aspects of prenatal diagnosis and clinical management. Alterations in a single or a few nucleotides account for most of the types of beta-thalassemia syndromes that have been characterized, and a variety of deletions have been found associated with beta O thalassemia, delta beta thalassemia, gamma delta beta thalassemia, and hereditary persistence of fetal hemoglobin (HPFH). Studies of nondeletional types of HPFH have revealed several single base changes 5' to the G gamma and A gamma genes, suggesting that these regions may be of major importance in the switchover from fetal to adult hemoglobin synthesis and in the relative production of the G gamma and A gamma globin chains during development. Evaluation of restriction enzyme polymorphisms and the assignment of haplotypes in the beta-like globin region of chromosome 11 have allowed delineation of the origin and distribution of thalassemia mutations, and have provided an important means for prenatal diagnosis. These studies have accumulated much new information about the function and expression of eukaryotic genes, and have served as a model for the investigation of human genetic disorders. The clinical management of patients with Cooley's anemia has benefited greatly from changes in transfusion practice, clear guidelines for splenectomy, and the availability of effective chelation therapy for iron overload. Current basic and clinical studies may lead to new approaches to management, treatment and eventual cures for this disease, including safe bone marrow transplantation, oral chelation treatment, and gene therapy.
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PMID:Overview of the beta thalassemias: genetic and clinical aspects. 246 34


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