A national registry of haemoglobinopathies in Greece: deducted demographics, trends in mortality and affected births.

Haemoglobinopathies are the most common hereditary disorders in Greece. Although there is a successful national prevention program, established 35 years ago, there is lack of an official registry and collection of epidemiological data for haemoglobinopathies. This paper reports the results of the first National Registry for Haemoglobinopathies in Greece (NRHG), recently organized by the Greek Society of Haematology. NRHG records all patients affected by thalassaemia major (TM), thalassaemia intermedia (TI), "H" Haemoglobinopathy (HH) and sickle cell disease (SCD). Moreover, data about the annual rate of new affected births along with deaths, between 2000 and 2010, are reported. A total of 4,506 patients are registered all over the country while the number of affected newborns was significantly decreased during the last 3 years. Main causes for still having affected births are: (1) lack of medical care due to financial reasons or low educational level; (2) unawareness of time limitations for prenatal diagnosis (PD); due either to obstetricians' malpractice or to delayed demand of medical care of couples at risk; and (3) religious, social or bioethical reasons. Cardiac and liver disorders consist main causes for deaths while life expectancy of patients lengthened after 2005 (p < 0.01). The NRHG of patients affected by haemoglobinopathies in Greece provides useful data about the haemoglobinopathies in the Greek population and confirms the efficacy of the National Thalassaemia Prevention Program on impressively decreasing the incidence of TM and sickle cell syndromes.

Variable and often severe phenotypic expression in patients with the α-thalassemic variant Hb Agrinio [α29(B10)Leu→Pro (α2)].

Hb Agrinio [α29(B10)Leu→Pro] is a highly unstable variant, classified as a nondeletional α-thalassemia (α-thal) mutation. To date it has only been described in individuals of Greek and Cypriot origin. Evaluation of the phenotypic presentation of 12 Hb Agrinio homozygotes or compound heterozygotes, diagnosed in a single center in Greece during a 15-year period, found a wide clinical expression, ranging from thalassemia intermedia (with or without transfusion requirement) to Hb H hydrops fetalis, with some phenotype-to-genotype correlation. The often severe clinical presentation of Hb Agrinio homozygotes or Hb Agrinio compound heterozygotes, coinheriting severe α-thal determinants, indicates that molecular identification of carriers of the Hb Agrinio mutation should be considered within the context of screening programs involving individuals of Greek and Cypriot origin. Selective molecular investigation of candidate carriers is facilitated by the observation that all heterozygotes for the Hb Agrinio mutation present with at least one hematological parameter implicating an α-thal carrier state.

Assessment of iron distribution between liver, spleen, pancreas, bone marrow, and myocardium by means of R2 relaxometry with MRI in patients with beta-thalassemia major.

PURPOSE: To investigate the correlation between the degree of hepatic, splenic, pancreatic, vertebral bone marrow (VBM), and myocardial siderosis, as expressed by relaxation rate (R2 = 1/T2) values, in patients with thalassemia. MATERIALS AND METHODS: R2 relaxation rate values of liver, spleen, VBM, pancreas, and myocardium were estimated in 68 consecutive transfusion-dependent patients with beta-thalassemia major and 10 healthy controls using a respiratory triggered 16-echo Carr-Purcell-Meiboom-Gill (CPMG) spin echo sequence. RESULTS: Hepatic R2 values were significantly increased in all 68 patients; VBM, pancreatic, and myocardial R2 values were increased in 67/68, 35/47, and 47/61 patients, whereas five patients showed decreased pancreatic R2 attributed to fatty degeneration. Of the 39 nonsplenectomized patients, splenic R2 values were decreased in 30 and normal in nine patients. Hepatic R2 values correlated with splenic (r = 0.63, P < 0.001), VBM (r = 0.52, P < 0.001), but not with myocardial and pancreatic R2 values. CONCLUSION: Despite positive correlations between the degree of hepatic, splenic, and VBM siderosis, as expressed by respective R2 values, there was variability of iron distribution patterns in thalassemic patients. Unpredictable patterns of iron distribution may be seen, such as normal signal of the spleen in the presence of siderotic liver, resembling primary hemochromatosis. Fatty degeneration of the pancreas was not uncommon.

The effect of 23-valent pneumococcal polysaccharide vaccine on immunological priming induced by 7-valent conjugate vaccine in asplenic subjects with beta-thalassemia.

The effect of the 23-valent pneumococcal polysaccharide vaccine (PPV) on the 7-valent conjugate (PCV) vaccine-induced priming was evaluated in 35 splenectomised beta-thalassemics [median (range) age: 30 (12-41) years] vaccinated with either PCV/PPV or two PCVs 1 month apart, followed by a PPV booster 12 months later. 28/35 had already received 1-3 PPVs in the past. Different schedules induced similar anamnestic responses; however priming for 3/5 serotypes induced by one or two PCVs, was inferior in subjects who had received > or =2 PPVs in the past when compared with 23 aged-matched PPV-naïve beta-thalassemics. One PPV following PCV does not affect PCV priming; multiple PPVs induce hyporesponsiveness for some serotypes in splenectomised subjects with beta-thalassemia.

Natural and vaccine-induced immunity against Haemophilus influenzae type b in patients with beta-thalassemia.

Natural and vaccine-induced immunity and immunological memory to Haemophilus influenzae type b (Hib) were evaluated in adolescents and adults with beta-thalassemia. At baseline 10/23 (43%) unvaccinated patients had naturally acquired anticapsular antibodies >0.15 microg/ml, the threshold of protection, compared to 9/10 (90%) aged-matched controls. Hib-conjugate vaccine (PRP-T) induced protective immune responses in all subjects and there were no differences in geometric mean concentrations at 1 month (GMC) between patients and controls (69.04 versus 40.5, respectively). Vaccine-induced immunological memory was assessed in 12 subjects with beta-thalassemia who had been vaccinated against Hib in the past. All subjects had retained PRP>1 microg/ml at baseline; PRP-T revaccination induced anamnestic responses which were similar, in terms of post vaccination antibody concentration (P=0.54) and avidity (P=0.08), with primary responses given by previously unvaccinated patients. A single dose of PRP-T induces adequate and long-lasting immunity and should be given in all unvaccinated adolescents and adults with beta-thalassemia.

R2 relaxometry with MRI for the quantification of tissue iron overload in beta-thalassemic patients.

PURPOSE: To evaluate the usefulness of a time-efficient MRI method for the quantitative determination of tissue iron in the liver and heart of beta-thalassemic patients using spin-spin relaxation rate, R2, measurements. MATERIALS AND METHODS: Images were obtained at 1.5 T from aqueous Gd-DTPA solutions (0.106-8 mM) and from the liver and heart of 46 beta-thalassemic patients and 10 controls. The imaging sequence used was a respiratory-triggered 16-echo Carr-Purcell-Meiboom-Gill (CPMG) spin-echo (SE) pulse sequence (TR = 2000 msec, TE(min) = 5 msec, echo spacing (ES) = 5 msec, matrix = 192 x 256, slice thickness = 10 mm). Liver iron concentration (LIC) measurements were obtained for 22 patients through biopsy specimens excised from the relevant liver segment. Biopsy specimens were also evaluated regarding iron grade and fibrosis. Serum ferritin (SF) measurements were obtained in all patients. RESULTS: A statistically significant difference was found between patients and healthy controls in mean liver (P < 0.004) and myocardium (P < 0.004) R2 values. The R2 values correlated well with Gd DTPA concentration (r = 0.996, P < 0.0001) and LIC (r = 0.874, P < 0.0001). A less significant relationship (r = 0.791, P < 0.0001) was found between LIC measurements and SF levels. R2 measurements appear to be significantly affected (P = 0.04) by different degrees of hepatic fibrosis. The patients' liver R2 values did not correlate with myocardial R2 values (r = 0.038, P < 0.21). CONCLUSION: Tissue iron deposition in beta-thalassemic patients may be adequately quantified using R2 measurements obtained with a 16-echo MRI sequence with short ES (5 msec), even in patients with a relatively increased iron burden.

Clinical response and adverse events in young patients with sickle cell disease treated with hydroxyurea.

The authors studied the long-term clinical and hematological response to hydroxyurea (HU) therapy in young patients, with either S/beta-thalassemia (beta(thal)) (8 patients) or SS (6 patients). All patients with S/beta(thal) responded well to treatment. Longitudinal evaluation of Hb, HbF, and MCV showed a significant increase compared to baseline levels, but the pattern of HbF changes varied among patients. Changes in HbF and Hb correlated well with baseline HbF. Favorable clinical responses, as documented by decline in hospitalization days for vasoocclusive crisis and transfused units of packed red blood cells, were also noted. During treatment, 1 patient was diagnosed with Hodgkin's lymphoma and 2 patients developed bilateral avascular necrosis of the femoral head. HU seems to be effective in a high proportion of young patients with sickle cell disease and in particular with S/beta(thal), but cannot eliminate occurrence of serious adverse events.

Giant adrenal myelolipoma with minimal fat content in a patient with homozygous beta-thalassemia: appearance on MRI.

Giant adrenal myelolipoma is an uncommon entity. We present the atypical MR imaging findings of a giant adrenal myelolipoma in a patient with homozygous beta-thalassemia with histopathology correlation. The tumor showed a drop in signal on the opposed-phase images, with no evidence of macroscopic fat contents, and demonstrated very high signal intensity on T2-weighted images. Giant adrenal myelolipoma should be considered in the differential diagnosis of tumors with the combination of the above MR imaging characteristics.