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Objectives: Beta thalassaemia major (β-TM) and sickle-cell disease (SCD) are severe haemogobinopathies requiring life-lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs., Methods: Data of affected births between 01/01/1980 and 31/12/2009 were collected in a nationwide scale, and expected vs. observed rates of new births were calculated and compared. In a subpopulation of affected births of Greek origin, the causes for occurrence of the new affected birth were also collected and analysed., Results: Overall, the reduction in new cases was 81.1% and 84.6% for β-TM and SCD, respectively. For β-TM, a constant declining trend was recorded over the 30-yr period, whereas for SCD, a transient reversal was observed in the mid-1990s probably due to the significant influx of immigrants of African origin. Programme failure was 2.2 times more common among new β-TM births of Greek origin compared to new SCD cases (P < 0.001). Unawareness and parental choice were more frequent in SCD compared to β-TM (unawareness: OR = 1.4, P = 0.05, parental choice: OR = 1.9, P = 0.01). The main cause for programme failure was carrier misidentification and incorrect genetic advice for β-TM and SCD, respectively., Conclusions: The β-TM and SCD prevention programme in Greece has significantly reduced the numbers of new affected births. The outcomes could be optimised in groups of non-Greek origin, in carrier identification and by offering specialised genetic counselling., (© 2013 John Wiley & Sons A/S.)

Purpose: To evaluate whether the introduction of magnetic resonance imaging (MRI) in the management of thalassemia major (TM) patients has affected the risk of cardiac death., Materials and Methods: In all, 804 TM patients from two large reference units were included and the risk of dying of cardiac causes, before and after their first MRI, was assessed by a Cox proportional hazards model with time-dependent covariates., Results: Adding information from MRI reduced the risk of cardiac death from 6.0 deaths/1000 patient-years to 3.9 deaths/1000 patient-years (P = 0.22). The risk of cardiac death before having an MRI study was 82% higher compared to the risk observed after the first MRI., Conclusion: MRI has become a vital component of ongoing management and seems to have a beneficial effect on cardiac mortality in TM., (Copyright © 2011 Wiley-Liss, Inc.)

Background: With transfusions and chelation therapy, the prognosis for transfusion-dependent beta thalassaemia has changed from being fatal in early childhood to a chronic disorder with prolonged survival., Design and Methods:   In this historical prospective study, we present survival, causes of death and mortality ratios compared to the general population in 1044 Greek patients with transfusion-dependent beta thalassaemia., Results:   At the age of 50years, the overall survival was 65.0%, while the cardiac death-free survival was 77%. Birth cohort had a significant effect on survival (P<0.001) with a negative trend towards past decades. The standardised mortality ratio (standardised for sex and ages 20-40years) compared to the general population improved significantly from 28.9 in 1990-1999 to 13.5 in 2000-2008, while the standardised cardiac mortality ratio reduced from 322.9 to 106.6, respectively., Conclusions:  Survival in thalassaemia has dramatically improved over the last twenty years but mortality remains significantly increased, compared to the general population., (© 2011 John Wiley & Sons A/S.)

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.

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.

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., (Copyright 1998 by The American Society of Hematology)

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.