RESUMEN
Arterial and stromal elastorrhexis, an elastic tissue disorder, was recently described in beta-thalassaemia major. Histopathological material from 10 patients with thalassaemia intermedia, 14 with sickle cell thalassaemia and 18 with hereditary spherocytosis was examined in order to investigate the specificity of the arteriopathy. Histological re-examination was made in a total of 42 spleens with parasplenic lymph nodes in 14 cases, 26 surgical liver biopsies and 16 gallbladders with associated regional lymph nodes. Arteriopathy, qualitatively similar to that seen in beta-thalassaemia major, was found in up to 90% of extrasplenic muscular arteries. Elastorrhexis lesions were also found in intrasplenic arteries and in stromal elastic tissue of spleens and parasplenic lymph nodes, in the absence of tissue iron overload. The arteriopathy appears in the first decade of life even in spleens of normal weight, and seems unrelated to the severity of permanent anaemia. It is suggested that patients suffering from hereditary chronic haemolytic diseases are subject to an elastic tissue disorder which is similar to hereditary pseudoxanthoma elasticum, the earliest and most frequent manifestation of which is arterial elastorrhexis of muscular extrasplenic arteries.
Asunto(s)
Anemia de Células Falciformes/patología , Tejido Elástico/patología , Esferocitosis Hereditaria/patología , Talasemia beta/patología , Niño , Preescolar , Femenino , Humanos , Ganglios Linfáticos/patología , Masculino , Seudoxantoma Elástico/patología , Bazo/patología , Arteria Esplénica/patología , SíndromeRESUMEN
Pseudoxanthoma elasticum-like lesions of the eye and skin are frequently observed in beta-thalassaemia, and there has been speculation about associated vascular lesions. This led to our study of histopathological material from thalassaemic patients. Histological re-examination was made of a series of 45 spleens and 45 surgical liver biopsies from 45 patients with beta-thalassaemia major, aged 6-25 yr and treated over the 20-yr period 1975-95. Correlations between clinical, laboratory and histological findings were demonstrated by statistical analysis. Arteriopathy characterized by fragmentation and multiple defects of the internal elastic lamina ('arterial elastorrhexis'), with deposits of iron and calcium salts, was found in the hilar arteries of the spleen with a frequency of 96%. Similar lesions were observed in the parenchymal arteries and the stromal elastic tissue ('stromal elastorrhexis') of the spleen, liver and lymph nodes. Arterial and elastic tissue alterations appear in the first decade of life and become generalized over the course of the disease, independent of the time of onset of transfusion and iron chelation therapy. Arterial elastorrhexis is the earliest and most frequent manifestation of a systemic elastic tissue disorder in beta-thalassaemia major. It appears to be an acquired pseudoxanthoma elasticum-like syndrome, related primarily to tissue hypoxia and disturbance of elastin metabolism.
Asunto(s)
Arterias/patología , Tejido Elástico/patología , Enfermedades Vasculares/etiología , Enfermedades Vasculares/patología , Talasemia beta/complicaciones , Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Talasemia beta/patologíaRESUMEN
In homozygous beta-thalassemia, the organ damage is mainly attributed to excessive iron deposition through the formation of oxygen free radicals. Despite appropriate transfusion and chelation therapy and low ferritin levels, patients still develop organ failure, heart failure being the main cause of death. This study was designed to determine whether the decreased antioxidant activity of the apolipoprotein E (APOE) 4 allele could represent a genetic risk factor for the development of left ventricular failure (LVF) in beta-thalassemia homozygotes. A total of 251 Greek beta-thalassemia homozygotes were studied. Patients were divided in three groups: group A (n = 151) with no cardiac impairment, group C (n = 47) with LVF, and 53 patients with LV dilatation and normal LV systolic function constituted the group B. DNA was obtained from all patients, and the polymerase chain reaction was used to analyze the polymorphism at the APOE locus. The APOE allele frequencies were compared with those of a Greek control sample of 216 healthy blood donors. Patients with no cardiac impairment had an APOE 4 allele frequency (7.9%) not different from population controls (6.5%, P > .05), while patients with LVF had a significantly higher frequency of APOE 4 (12.8%) than the controls (P < .05, odds ratio = 2.11, 95% confidence interval 1.03 to 4.32). The APOE 4 allele may represent an important genetic risk factor for the development of organ damage in homozygous beta-thalassemia.
Asunto(s)
Apolipoproteínas E/genética , Insuficiencia Cardíaca/etiología , Disfunción Ventricular Izquierda/etiología , Talasemia beta/complicaciones , Adolescente , Adulto , Alelos , Apolipoproteína E4 , Transfusión Sanguínea , Terapia por Quelación , Niño , Cromosomas Humanos Par 19/genética , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Grecia/epidemiología , Insuficiencia Cardíaca/epidemiología , Homocigoto , Humanos , Hierro , Masculino , Persona de Mediana Edad , Oxidación-Reducción , Estrés Oxidativo , Polimorfismo Genético , Especies Reactivas de Oxígeno , Factores de Riesgo , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/epidemiología , Talasemia beta/tratamiento farmacológico , Talasemia beta/etnología , Talasemia beta/genética , Talasemia beta/terapiaRESUMEN
Pregnancy in beta-thalassemic patients has become a not unusual event, especially in the last 10 years. The course and outcome of 19 pregnancies in 16 thalassemic women, followed in our unit, 12 with thalassemia major and 4 with thalassemia intermedia, were studied. Genetic counselling was provided and counselling regarding the planning or the continuation of the pregnancy was based mainly on cardiac performance at rest. Cardiac, endocrine and liver function were evaluated at baseline, monitored throughout pregnancy and reevaluated after delivery. Desferrioxamine treatment was discontinued as early as possible. During pregnancy the Hb level was maintained at about 10 g/dl in all women by transfusion. The course of pregnancy was essentially uneventful and elective Cesarean section was performed in all cases. The mean birth weight of the newborns was 3000 g. All babies were normal except for one with exomphalus. Pregnancy was well tolerated by the heart in all women and no endocrinological disorders were observed. In conclusion, pregnancies in beta-thalassemia can be safe for both mothers and their babies with careful selection and appropriate care.
Asunto(s)
Infertilidad Femenina/etiología , Complicaciones Hematológicas del Embarazo , Talasemia beta/complicaciones , Adulto , Cesárea , Quelantes/administración & dosificación , Deferoxamina/administración & dosificación , Glándulas Endocrinas/fisiopatología , Femenino , Grecia , Corazón/fisiopatología , Humanos , Hígado/fisiopatología , Embarazo , Resultado del Embarazo , Talasemia beta/fisiopatologíaRESUMEN
UNLABELLED: The urinary levels of the lysosomal enzymes N-acetyl-beta-D-glucosaminidase (NAG) (EC 3.2.1.52) and alpha-mannosidase (EC 3.2.1.24) were evaluated in patients with beta-thalassaemia major and normal control subjects. Two groups of patients with different degrees of iron overload, as judged by their serum ferritin levels, were investigated. Renal disease was not present in any of the patients. A statistically significant increase in the levels of NAG was observed in the high ferritin (> 3,000 mg/dl) group compared to the low ferritin (< 3,000 mg/dl) and the control groups. No difference was observed in the urinary alpha-mannosidase levels between the groups examined. The finding of increased NAG levels in the patients with the increased iron load suggests that kidney lysosomes are a target of iron toxicity. The different behaviour of the two lysosomal enzymes may reflect the intra- and inter-lysosomal heterogeneity in kidney. CONCLUSION: Iron overload resulted in increased urinary levels of the lysosomal enzyme NAG which has been proposed as an early marker of kidney damage. Reduction of iron load, achieved by regular desferrioxamine infusion, resulted in normalisation of the urinary enzyme levels. Thus kidney lysosomes appear to be a target and possibly a mediator of iron toxicity in this tissue.
Asunto(s)
Ferritinas/sangre , Hexosaminidasas/orina , Sobrecarga de Hierro , Manosidasas/orina , Talasemia beta/enzimología , Adolescente , Adulto , Análisis de Varianza , Biomarcadores/sangre , Biomarcadores/orina , Estudios de Casos y Controles , Terapia por Quelación , Niño , Preescolar , Femenino , Humanos , Masculino , Talasemia beta/terapiaRESUMEN
In order to develop an objective test for discriminating between patients with thalassaemia intermedia requiring blood transfusion, and those not likely to require transfusion the medullary width (MW) in the midpoint of the second left metacarpal and the bone mass were measured in 34 normal children and in 37 patients. In patients, blood haemoglobin (Hb) and serum ferritin concentration were measured and cephalofacial deformities (CFD) were scored. The mean values of MW were 0.37 +/- 0.06 and 0.44 +/- 0.1 cm (P less than 0.01) and the bone mass 0.091 +/- 0.012 and 0.078 +/- 0.02 (P less than 0.005) in normal children and patients, respectively. In 13 of these patients who had MW more than 2 SD above the mean of the controls, i.e. more than 0.5 cm, regular blood transfusions were instituted. Measurements of MW 12 and 1 month before and 12 months after the initiation of transfusions showed an increase from 0.50 to 0.60 and a decrease to 0.49, respectively. Bone mass measured at the same times decreased from 0.083 to 0.045 and increased to 0.071, respectively. These changes were visible radiologically. It is concluded, therefore, that the measurement of MW seems to be an objective, simple test for discriminating between patients requiring or not blood transfusions, and that bone deformities will be reversible if transfusions are instituted using as criterion the MW (greater than 0.5 cm) regardless of age or haemoglobin concentration. This test may help clinicians to decide about the optimal time for institution of regular transfusions in patients with thalassaemia intermedia.