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Background Beta-thalassemia major patients are at increased risk of complications including endocrinopathies and bone disease due to iron overload. So, this study aimed to assess the growth parameters, serum levels of 25-OH-vitamin D, calcium, and phosphorous in children with beta-thalassemia major. This was a case-control study that included 55 children with beta-thalassemia major compared with 30 sex- and age-matched healthy children that served as a control group. All enrolled children were subjected to full history taking, clinical examination including anthropometric measurements, and laboratory investigations including complete blood count, serum ferritin, levels of serum calcium, phosphorus, and 25-OH-vitamin D. Results Body mass index was statistically significantly lower in the thalassemic group (P < 0.001). It was observed that vitamin D levels were significantly lower in thalassemic patients than in controls (P value < .0001). The mean serum 25-OH-vitamin D levels were 19.84 ± 5.79 ng/ml and 44.98 ± 5.77 ng/ml, respectively; 22 cases (40%) had insufficient vitamin D, and 5 cases (9%) had deficient vitamin D. Regarding serum calcium and phosphorous, there was no significant difference between the thalassemic and control groups. Conclusion Children with beta-thalassemia major had low body mass index and metabolic abnormality in the form of lower serum levels of vitamin D that signify the importance of therapeutic interventions.

Background:Beta-thalassemia is an autosomal recessive hemoglobinopathy with frequent skeletal complications, often debilitating in adolescent patients. We aim to evaluate the bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) and ascertain osteoporosis/osteopenia frequency in patients with β-thalassemia major. Methodology:In this cross-sectional study, 36 adolescent patients with β-thalassemia major were enrolled from June 2015 to March 2017. BMD was measured in the anteroposterior lumbar spine (L1-L4) and femoral neck by DEXA. For the biochemical estimations, blood and urine samples were obtained and analyzed. The results of a bone density test were presented as T and Z scores. Results:There were 20 male and 16 female patients with a mean age of 21.33 ± 3.7 years. The mean bone mineral content (BMC) was 20.10 ± 6.0 gm, and the mean BMD was 0.65 ± 0.07 gm/cm2. The mean T score was -3.17 ± 1.04, and the Z score was -3.06 ± 1.06. All patients had low BMD, as depicted by their T or Z scores. The reported frequency of osteoporosis and osteopenia was 77.7% and 22.2%, respectively. Conclusion:All Beta-thalassemia major patients had low BMD with a remarkable incidence of osteoporosis. It is recommended to perform an annual BMD among thalassemic patients to prevent fatal consequences and achieve an optimal bone density among such patients. Link:http://aeirc-edu.com/ojs14/index.php/IJEHSR/article/view/334/661

β-thalassemia are a group of inherited blood disorders with reduced hemoglobin levels. β-thalassemia major is the severe form of disease, and the patients often display an array of associated organ dysfunction which thus increase the risk associated with surgery and anesthesia. Patients with β-thalassemia major can have multiple pathological defects that may lead to thromboembolic events. Here, we report such a case who was complicated by occurrence of cerebral sinus thrombosis and presented for decompressive hemicraniectomy under general anesthesia. The anesthetic challenges during in such scenario have been discussed.

β‐thalassemia major is an inherited hemoglobinopathy that requires lifelong red blood cell transfusions and iron chelation therapy to prevent complications due to iron overload. Traditionally, β‐thalassemia has been more common in certain regions of the world such as the Mediterranean, Middle East, and Southeast Asia. However, the prevalence of β‐thalassemia is increasing in other regions, including Northern Europe and North America, primarily due to migration. This review summarizes the available data on the changing incidence and prevalence of β‐thalassemia as well as factors influencing disease frequency. The data suggest that the epidemiology of β‐thalassemia is changing: Migration has increased the prevalence of the disease in regions traditionally believed to have a low prevalence, while, at the same time, prevention and screening programs in endemic regions have reduced the number of affected individuals. Various approaches to prevention and screening have been used. Region‐specific prevention and treatment programs, customized to align with local healthcare resources and cultural values, have been effective in identifying patients and carriers and providing information and care. Significant challenges remain in universally implementing these programs.

Background: Management of beta-thalassemia major (TM) requires life-long hemotransfusions leading to iron overload. Iron elimination is enhanced by the use of modern chelators. Aim: To assess the effect of modern chelation therapy by dynamics of serum ferritin concentration and liver MRI T2*. Patients and methods: Forty-six patients with TM (male to female ratio =1:1, mean age 33.2±10.9 years) were prospectively studied between 2011 and 2014. Twenty-one patients (45.7%) were treated with deferasirox, 17 (37%) – with deferiprone, and 8 (17.3%) – with deferiprone in combination with deferoxamine. Ferritin was measured by ELISA. MRI T2* was assessed by Siemens Magnetom Avanto 1.5T. The patients were allocated into 3 groups based on their initial ferritin level and liver MRI T2*. Statistical analysis was performed using SPSS v. 18 for Windows. Data were analysed by descriptive analysis, analysis of variance and correlative analysis, means were compared using t-test and one-way ANOVA. Results: In 2011, 9 (19.5%) patients had normal liver MRI T2*; in 2014 they were 17 (37%). The patients with mild grade liver siderosis were 12 (26%) in 2011, and in 2014 they were 14 (30.4%). In 2011, the patients with moderate liver siderosis were 14 (30.4%), and in 2014 – 12 (26.0%). Eleven patients (23.9%) had severe liver siderosis in 2011 and only two patients (4.0%) were diagnosed with the condition in 2014. Conclusion: A reduction of iron overload was found in all studied groups. This positive effect is attributed to the use of modern chelators and the ease of access to accurate monitoring.

Background : Beta-thalassemia major patients require repeated blood transfusion which is associated with iron overload in different organs such as heart, liver, kidney and their related complications. In this study the effects of selenium in iron overload related complications of patients with beta-thalassemia major were assessed. Methods: In this clinical trial, 34 beta-thalassemia major patients over 12 years old were enrolled. Patients with severe renal failure, history of selenium consumption over the last three months, change of blood transfusion pattern, and any change of chelating agent were excluded from the study. For all patients, tablet of selenium 200 µg/day was administered for a month. Blood samples were taken at baseline and after one-month to assess the level of ferritin, total iron-binding capacity (TIBC), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (Scr), selenium. Hair loss was assessed by questionnaire before and after intervention. Results: From 34 patients, 27 (79.4%) had deficient level of selenium at baseline. The selenium level was increased after intervention (p=0.005). The level of serum ALT and Scr decreased remarkably after one-month selenium consumption (p=0.007 for both). In addition, the AST level decreased remarkably after intervention (p=0.053). Severe hair loss profile has improved significantly after supplementation (p=0.004). Conclusion: One-month selenium consumption improved liver and kidney function related markers remarkably. Moreover, selenium improved hair profile and severe hair loss in thalassemia patients. Further studies are needed on the effect of selenium administration on liver and kidney function.

Beata thalassemia Beta thalassemia syndrome by reduction or absence of B-globin chain synthesis. Without iron chelation therapy (ICT) the regular blood transfusion would increase the iron stores to several times. Endocrine glands are vulnerable to iron overload causing endocrine dysfunction. Iron deposition within the parathyroid gland causes hypoparathyroidism particularly after ten years of age. Pancreatic islets are very susceptible to oxidative damage due to iron overload; their high divalent metal expression makes them highly susceptible to iron-catalyzing oxidative stress. The pathogenicity of osteopathy in is multifactorial comprising environmental (diet and lifestyle), iatrogenic (medicines), genetic and acquired factors (expansion of bone marrow, hemochromatosis, deficiency of growth hormone, hepatitis and hypogonadism).The increase in blood transfusion and RBCs break down in addition to iron accumulation and deposition are the main factors causing splenomegaly. Liver disease is one of the major complications affecting patients with B TM.Liver damage is multifactorial with iron overload is considered the main causative factor, as well as hepatitis C (HCV) and hepatitis B (HBV) infections which are acquired on recurrent blood transfusions. The free radicals of deposited iron overcome the cellular antioxidant mechanisms resulting in peroxidative cellular injury. As a result, iron overload is the leading cause of left ventricular cardiomyopathy development

Aim: A thrombosis and inflammation marker, Signal peptide-CUB (complement C1r/C1 s)-EGF (epidermal growth factor)-like domain-containing protein 1 (SCUBE-1) is expressed in endothelial cells and activated platelets. We aimed to investigate the levels of this marker in patients with Thalassemia major (TM), a disease which causes a tendency to thrombosis.Methods: Twenty patients with TM and age and gender-matched twenty healthy controls were included in this prospective case-control study. Other thrombosis markers such as D-dimer and homocysteine were studied in addition to SCUBE-1 in both groups.Results: The SCUBE1 and D-dimer levels were higher in the TM group compared to the control group (P=0.004, P=0.023, respectively). A significant positive correlation was detected between platelet count and SCUBE1 (r=0.342, P=0.031).Conclusion: We detected elevated SCUBE1 levels in children with TM compared to the healthy controls, which correlated with platelet count. SCUBE1 may be used as a thrombosis marker in TM in the early stages of the disease., Amaç: Sinyal peptidi-CUB (tamamlayıcı C1r / C1s) -EGF (epidermal büyüme faktörü) benzeri alan içeren protein 1 (SCUBE-1), endotel hücreleri ve aktive olmuş trombositlerde eksprese edilen tromboz ve inflamasyon belirteci olarak kullanılan bir proteindir. Tromboza eğilim yaratan bir hastalık olan talasemi majörde bu belirtecin düzeylerini incelemeyi amaçladık.Yöntemler: Bu kesitsel vaka-kontrol çalışmasına SCUBE-1 düzeylerini belirleyebilmek için 20 talasemi majorlü hasta ve kontrol grubu olarak da benzer yaş ve cinsiyette 20 sağlıklı çocuk dahil edildi. D-dimer, homosistein gibi diğer tromboz belirteçleri SCUBE-1 ek olarak her iki grupta çalışıldı.Bulgular: Gruplar arasında SCUBE-1 ve D-dimer düzeyleri açısından anlamlı fark vardı (P=0,004, P=0,023, sırasıyla). Trombosit sayısı ile SCUBE-1 arasında anlamlı pozitif korelasyon tespit edildi (r=0,342, P=0,031).Sonuç: SCUBE-1 seviyelerinin talasemi majorlü çocuk hastalarda sağlıklılara nazaran yüksek olduğunu ve trombosit sayısı ile korele olduğunu tespit ettik. SCUBE-1 belki erken evrelerde tromboz belirteci olarak kullanılabilir.

Background β-thalassemia major is a hereditary disorder of hemoglobin (Hb) that results in defective Hb synthesis, leading to severe chronic anemia. The mainstay of its treatment is lifelong regular packed red cell transfusions associated with iron-chelating therapy. Globally, there is a gap between blood donation and the actual needs of the patients who depend on transfusion. Patients with β-thalassemia major are no exception and have limited access to regular and safe blood transfusions. This study aimed to assess the gap between the demand and supply of blood for transfusion-dependent patients with β-thalassemia major treated at the Hereditary Blood Diseases Center, Al Ahsa, Eastern Saudi Arabia. Methodology This was a retrospective, cross-sectional study conducted at the Hereditary Blood Disease Center, Al Ahsa, Saudi Arabia, including patient data from January 2017 to December 2019. We used Excel 365 from Microsoft Office 2016, version 1706. Results A total of 158 patients were on chronic transfusion. Of the total patients, 65% were adults, while the remaining 35% comprised the pediatric population. The total number of units requested and received during the three-year period was 14,509 and 9,530, respectively, indicating a gap of 4,979 (34%) units. The age of most of the units received was more than 14 days: 36% of those in 2017, 49.9% in 2018, and 61.5% in 2019. Rare blood groups and alloimmunization accounted for

Due to the high transfusion volume, polytransfused patients with sickle cell disease (SCD) and beta-thalassemia are constantly exposed to parenterally transmitted infections. Currently, we have little information about the virome of such patients and how the virological composition might be influenced by the hemotherapy procedures that these patients receive. The objective of this study was to compare the viral diversity between these two groups with respect to the viral abundance and how it might be affected by the specific conditions of these groups. We sequenced by next-generation sequencing (NGS) and compared the virome of 30 patients with beta-thalassemia major, 45 with SCD, and 16 blood donors from the Blood Center of Ribeirao Preto, Brazil. Predominantly, commensal viruses including Torque teno virus (TTV) genotypes and human pegiviris-1 (HPgV-1) were identified in each group. Strikingly, while HPgV-1 reads were dominant in the SCD group, thalassemic patients showed high TTV abundance, expressed both in viral reads and genotypes. We speculated that the commensal virome of polytransfused patients might be influenced by the transfusion frequency and disease characteristics and that commensal viruses might be used as important genetic biomarkers for these hematological disturbances. Nevertheless, more specific studies are necessary to confirm a relationship between blood virome and transfusion treatment.

BACKGROUND Cardiac MRI plays a critical role in the management of thalassemic patients. No accurate biventricular reference values are available. PURPOSE To establish the ranges for normal left ventricular (LV) and right ventricular (RV) volumes and ejection fraction (EF) and LV mass normalized to body surface area (BSA), age, and gender in a large cohort of well-treated beta-thalassemia major (β-TM) patients without heart damage using a multiparametric MRI. STUDY TYPE Retrospective/cohort study. POPULATION In all, 251 β-TM patients with no known risk factors or cardiac disease, normal electrocardiogram, no macroscopic myocardial fibrosis, and all cardiac segments with T2 * ≥20 msec, and 246 healthy subjects. FIELD STRENGTH/SEQUENCE 1.5T/cine steady-state free precession (SSFP), gradient-echo T2 *, late gadolinium enhancement (LGE) images. ASSESSMENT Biventricular end-diastolic volume, end-systolic volume, stroke volume, and LV mass were normalized to BSA (EDVI, ESVI, SVI). STATISTICAL TESTS Comparisons between the two groups was performed with two-samples t-test or Wilcoxon's signed rank test. For more than two groups, one-way analysis of variance (ANOVA) or a Kruskal-Wallis test were applied. RESULTS Compared to controls, males with β-TM showed significantlt higher LVEDVI in all the age groups, while for the other volumes the difference was significant only within one or more age groups. In females the volumes were comparable between β-TM patients and healthy subjects in all the age groups. In the male β-TM population we found a significant effect of age on LVEDVI (P = 0.017), LVESVI (P = 0.001), RVESVI (P = 0.029), and RVEF (P = 0.031), while for females none of the biventricular parameters were significantly different among the age groups (LVEDVI: P = 0.614; LVESVI: P = 0.449; LVSVI: P = 0.186; LV mass index: P = 0.071; LVEF: P = 0.059; RVEDVI: P = 0.374; RVESVI: P = 0.180; RVSVI: P = 0.206; RVEF: P = 0.057). In β-TM patients all biventricular volume indexes as well as the LV mass index were significantly larger in males than in females (P

Patients with beta-thalassemia major (β-ΤΜ) may develop cardiac arrhythmias through a multifactorial mechanism. The current study evaluated the association of cardiac structure and function on echocardiography with atrial ectopic burden on 24-hour tape recording in β-ΤΜ patients. This prospective study included consecutive β-ΤΜ patients. Demographic, laboratory, echocardiographic, cardiac magnetic resonance (CMR) T2* and 24-hour tape recording data were prospectively collected. The patients were classified according to the median value of premature atrial contractions (PACs) on 24-hour tape. In total, 50 β-TM patients (37.6 ± 9.1 years old, 50% male) were divided in 2 groups; PACs ≤ 24/day and > 24/day. Patients with PACs > 24/day were treated with blood transfusion for a longer period of time (39.0 ± 8.6 vs. 32.0 ± 8.9 years, p < 0.007), compared to their counterparts. Older age (OR: 1.121, 95% CI: 1.032–1.217, p = 0.007), longer duration of blood transfusion (OR:1.101, 95% CI:1.019–1.188, p = 0.014), larger LV end-diastolic diameter (OR: 4.522, 95% CI:1.009–20.280, p = 0.049), higher values of LA peak systolic strain (OR: 0.869, 95% CI: 0.783–0.964, p = 0.008), higher MV E/E′ average (OR: 1.407, 95% CI: 1.028–1.926, p = 0.033) and higher right ventricular systolic pressure (OR: 1.147, 95% CI: 1.039–1.266, p = 0.006) were univariably associated with PACs > 24/day. LA peak systolic strain remained significantly associated with PACs > 24/day after adjusting for the duration of blood transfusions or for CMR T2*. The multivariable model including blood transfusion duration and LA peak systolic strain was the most closely associated with PACs > 24/day. Receiver operating characteristic curve analysis identified a left atrial peak systolic strain of 31.5%, as the best cut-off value (83% sensitivity, 68% specificity) for prediction of PACs > 24/day. In β-TM patients, LA peak systolic strain was associated with the atrial arrhythmia burden independently to the duration of blood transfusions and CMR T2*.

Cardiac complications are the most important cause of mortality and morbidity in Beta-Thalassemia Major (B-TM). The aim of our study was to determine the influence of Average Annual Mean Serum Ferritin (AAMSF) levels on cardiac function in patients suffering from B-TM. In this cross-sectional study, 50 patients of 5-15 years with B-TM were enrolled in the absence of clinical signs and symptoms of cardiac dysfunction. Left ventricular function was studied by using tissue Doppler image (TDI), pulse wave Doppler (PWD). AAMSF level was measured for 12 months. Patient groups were subdivided into two groups, group A with AAMSF level below 1000 ng/ml and group with B with AAMSF level above 1000 ng/ml. The Case group included 24(48%) males and 26(52%) females which were compared with 50 healthy subjects composed of 27(54%) males and 23 (46%) females (control group). The AAMSF Levels were 1054.60±687.95 ng/ml. By using PDW, in patients with AAMSF below 1000 ng/ml, The Parameters of the E, A, E/A E-DT had no significant difference with health groups (P=0.808, P=0.820, P=0.231 and P=0.061, respectively). No significant difference was revealed in parameters of E’, IVCT and ET in patients with AAMSF below 1000 ng/ml by using TDI in comparison to control (P=0.155, P=0.683, P=0.222, respectively).however, other TDI indexes including A’, E’/A’, IVRT, S,’ LVMPI, E/E’ had a significant difference with health group (P=0.014, P=0.041, P=0.045, P=0.002, P=0.021, and P=0.002, respectively). At patients with above AAMSF 1000 ng/mL, both PDW and TDI parameters had significant differences with the health group. There was no correlation among AAMSF levels and PWD or TDI indexes. The evidence from this study suggests that subclinical systolic and diastolic LV dysfunction has happened with AAMSF level above 1000 ng/ml, and according to our result, TDI is found more useful than PWD for subclinical cardiac evaluation.

This study was conducted to evaluate the cardiac perfusion and function of patients with beta-thalassemia major (TM) using 99mTc-MIBI cardiac gated single-photon-emission computed tomography (SPECT) and to compare the obtained indices with echocardiographic and hematological parameters. Patients with TM who were referred for regular blood transfusion and periodic checkup were included in this study. A questionnaire containing demographic and medical data was provided for all patients by an expert pediatrician. All of the patients were on Desferal chelation therapy and none of them had clinical signs of heart failure. Myocardial gated perfusion SPECT, echocardiography, and complete blood tests were performed for each patient. In total, 24 patients including 14 men (58.3%) and 10 women (41.7%) aged 15–36 years with a mean age of 24.3 ± 6.5 years' old were enrolled in this study. Myocardial perfusion scan (MPS) was normal in all patients. The mean value of the measured left ventricular ejection fraction (LVEF) was 58.88 ± 13.45%. There was no significant association between measured LVEF on scan and echocardiography (P > 0.05). In terms of hematological results, there was a significant association between the hemoglobin and ferritin level and the amount of blood transfusion (P = 0.02 and P= 0.00, respectively). According to the results of myocardial perfusion imaging (MPI), cardiac perfusion and LVEF were within normal limits in all asymptomatic patients. In the absence of any perfusion abnormality, the use of MPI in patients with asymptomatic beta-TM is not recommended for diagnosing myocardial ischemia.

Background The clinical application of cardiovascular magnetic resonance (CMR) T2 and T2* mapping is currently limited as ranges for healthy and cardiac diseases are poorly defined. In this meta-analysis we aimed to determine the weighted mean of T2 and T2* mapping values in patients with myocardial infarction (MI), heart transplantation, non-ischemic cardiomyopathies (NICM) and hypertension, and the standardized mean difference (SMD) of each population with healthy controls. Additionally, the variation of mapping outcomes between studies was investigated. Methods The PRISMA guidelines were followed after literature searches on PubMed and Embase. Studies reporting CMR T2 or T2* values measured in patients were included. The SMD was calculated using a random effects model and a meta-regression analysis was performed for populations with sufficient published data. Results One hundred fifty-four studies, including 13,804 patient and 4392 control measurements, were included. T2 values were higher in patients with MI, heart transplantation, sarcoidosis, systemic lupus erythematosus, amyloidosis, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) and myocarditis (SMD of 2.17, 1.05, 0.87, 1.39, 1.62, 1.95, 1.90 and 1.33, respectively, P 2 values in iron overload patients (SMD = − 0.54, P = 0.30) and Anderson-Fabry disease patients (SMD = 0.52, P = 0.17) did both not differ from controls. T2* values were lower in patients with MI and iron overload (SMD of − 1.99 and − 2.39, respectively, P 2* values in HCM patients (SMD = − 0.61, P = 0.22), DCM patients (SMD = − 0.54, P = 0.06) and hypertension patients (SMD = − 1.46, P = 0.10) did not differ from controls. Multiple CMR acquisition and patient demographic factors were assessed as significant covariates, thereby influencing the mapping outcomes and causing variation between studies. Conclusions The clinical utility of T2 and T2* mapping to distinguish affected myocardium in patients with cardiomyopathies or heart transplantation from healthy myocardium seemed to be confirmed based on this meta-analysis. Nevertheless, variation of mapping values between studies complicates comparison with external values and therefore require local healthy reference values to clinically interpret quantitative values. Furthermore, disease differentiation seems limited, since changes in T2 and T2* values of most cardiomyopathies are similar.

Graphical abstract, Patients with beta-thalassemia major (BTM) suffer from fatigue, poor physical fitness, muscle weakness, lethargy, and cardiac complications which are related to an energy crisis. Carnitine and acylcarnitine derivatives play important roles in fatty acid oxidation, and deregulation of carnitine and acylcarnitine metabolism may lead to an energy crisis. The present study aimed to investigate carnitine and acylcarnitine metabolites to gain an insight into the pathophysiology of BTM. Dried blood spots of 45 patients with BTM and 96 age-matched healthy controls were analyzed for free carnitine and 24 acylcarnitines by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Although medium chain acylcarnitine levels were similar in the patients with BTM and healthy controls, free carnitine, short chain acylcarnitines, long chain acylcarnitines, and total acylcarnitine levels were significantly lower in patients with BTM than in the healthy controls (P

OBJECTIVES: Early detection of iron loading is affected by the reproducibility of myocardial contour assessment. A novel semi-automatic myocardial segmentation method is presented on contrast-optimized composite images and compared to the results of manual drawing.MATERIALS AND METHODS: Fifty-one short-axis slices at basal, mid-ventricular and apical locations from 17 patients were acquired by bright blood multi-gradient echo MRI. Four observers produced semi-automatic and manual myocardial contours on contrast-optimized composite images. The semi-automatic segmentation method relies on vector field convolution active contours to generate the endocardial contour. After creating radial pixel clusters on the myocardial wall, a combination of pixel-wise coefficient of variance (CoV) assessment and k-means clustering establishes the epicardial contour for each segment.RESULTS: Compared to manual drawing, semi-automatic myocardial segmentation lowers the variability of T2* quantification within and between observers (CoV of 12.05 vs. 13.86% and 14.43 vs. 16.01%) by improving contour reproducibility (P < 0.001). In the presence of iron loading, semi-automatic segmentation also lowers the T2* variability within and between observers (CoV of 13.14 vs. 15.19% and 15.91 vs. 17.28%).CONCLUSION: Application of semi-automatic myocardial segmentation on contrast-optimized composite images improves the reproducibility of T2* quantification.

Beta-thalassemia major as a condition is dependent on multiple blood transfusions. In patients with multiple blood transfusions, the liver is the initial site of iron deposition progressing from fibrosis to cirrhosis. Ultrasonography diagnosis of liver fibrosis has prognostic significance and is helpful in risk stratification for assessing treatment options. This case report describes the sonological appearances of the liver in a 28-year-old female who was a recipient of regular blood transfusions and subsequently developed hepatic iron overload which presented as extensive periportal fibrosis masquerading as intraparenchymal mass lesions.

Objectives: To evaluate any association between the frequency of hereditary hemochromatosis (HFE) gene mutation (H63D and C282Y) and iron overload in beta-thalassemia major (BTM) patients. Methods: The case-control study was conducted from June 2016 to February 2018. Blood samples from 204 BTM patients and 204 normal controls were taken from the Sundas Foundation Blood Bank. These samples were analyzed for serum ferritin assay and HFE mutation. Ferritin level was measured on the ARCHITECT 1000SR. Both patient and control samples were analyzed for mutations using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: Serum ferritin levels for all patients were >1000ng/mL. The p.H63D mutation was observed in 23 (11.3%) cases, out of which 19 cases were heterozygous for p.H63D and 4 cases were homozygous. In control samples, 4 cases (2%) were found heterozygous for the p.H63D, and no homozygous mutation was found. Significantly high serum ferritin levels were found in BTM patients with the H63D mutation (p=0.00). In the case of p.C282Y, neither homozygous nor heterozygous mutation was found in patients or in controls. Conclusion: H63D polymorphism is associated with iron overload in BTM patients. Larger-scale research is required to give an elaborated view of the association of the HFE mutation with iron overload in these patients and to confirm our conclusion.

Thalassemia is a genetic disorder due to deletion or mutation in the gene for alpha or beta chain of hemoglobin. Gaucher’s disease (GD) is characterized by a deficiency of a lysosomal enzyme, glucocerebrosidase which occurs due to mutations in the GBA1 gene on chromosome 1. Thalassemia and GD have overlapping clinical manifestations and present with features such as anemia, hepatosplenomegaly, and skeletal involvement. This creates a diagnostic conundrum for physicians. We present a case of an 11-month-old female who presented with fever, increasing paleness, and labored breathing. She had a recent history of uncross-matched transfusion. The child showed signs of anemic failure. Physical exam findings strongly pointed towards hemolytic anemia due to thalassemia major. Genetic analysis confirmed homozygosity in Fr 8-9 mutation confirming beta thalassemia major. Bicytopenia along with visceromegaly indicated malaria or storage diseases. Enzyme analysis revealed low levels of beta-glucocerebrosidase with normal acid sphingomyelinase levels confirming GD. In our case, we report the association of beta thalassemia major with GD which is a rare entity. The report highlights the need for an independent assessment of disorders that have similar presentations to avoid missing an associated disorder.

A patient with beta-thalassemia major is known to have poor oral hygiene and a high risk of caries. Some studies showed that patients with beta-thalassemia have low salivary flow rate and acidic saliva. A reduction in salivary flow rate and pH would increase caries susceptibility. The aim of this study was to determine the correlation between salivary flow rate and pH with DMFT index in patients with beta-thalassemia major. This study was a cross-sectional design. A total of 38 patients with beta-thalassemia major aged more than 12 years old at Dr. Mohammad Hoesin Palembang Hospital were included in this study. Their unstimulated saliva was collected by spitting methods, and the teeth were examined with DMFT Index. The salivary flow rate was expressed as ml/min and the pH was measured using a saliva pH indicator paper. Data were analyzed using Pearson correlation test to determine the correlation between variables. The result showed that the mean age of the patients in this study was 16.6 years old, with a higher number of female patients than males. Patients with beta-thalassemia major had low salivary flow rate (0.72 ml/5 min), acidic saliva (6.34), and high DMFT index (8.34). This correlation was statistically significant (p

Beta-thalassemia major is characterized by a genetic deficiency in synthesis of beta-globin chains, resulting in reduced levels of functional hemoglobin. It is characterized by anemia, hepatosplenomegaly, and iron overload due to repeated blood transfusion. Hematopoietic stem cell transplantation is currently the only known curative treatment. We present a case of a 10-year-old girl with beta-thalassemia major who was successfully cured with allogeneic booster umbilical cord blood (UCB) transplantation with outcome data after 3 years of transplantation, in India. Postdiagnosis, she was on regular once-a-month blood transfusion until the age of 10 years, with no improvement. No serious adverse events occurred in the patient post-UCB transplantation. Chronic graft versus host disease was limited and was managed by medicines. Signs of primary graft rejection were also not seen.

Beta‐thalassemia major is one of the commonest hereditary hemoglobinopathies, characterized by reduced or absent beta‐globin chain synthesis 1. Management is based on regular blood transfusions to suppress ineffective erythropoiesis, with the goal to maintain pretransfusion hemoglobin concentration above 90 g/L 2. Repeated transfusions may lead to iron overload toxicity affecting the liver, spleen, heart, and endocrine system. Chelation therapy is used to mitigate against these complications. Endocrine complications from repeated transfusion include secondary hypogonadism (prevalence of 35–55%) 3, short stature (31–35%), diabetes mellitus (6–10%), primary hypothyroidism (3–11%), and hypoparathyroidism (1–7%) 3, 4. Iron deposition cardiomyopathy is the leading cause of morbidity and mortality in patients with thalassemia with consequent congestive cardiac failure accounting for up to 70% of deaths in patients with thalassemia 3. The coexistence of diabetes in patients with thalassemia leads to an increased risk for myocardial fibrosis 5, while diabetes and hypogonadism are independently associated with myocardial iron loading 6. In conditions such as hypertrophic and dilated cardiomyopathy, fibrosis increases the risk of dysrhythmias and heart failure. In thalassemia, although the cardiac burden is principally driven by iron loading per se, fibrosis might further increase the risk of cardiac dysfunction. This case report describes the congruence of multi‐organ dysfunction in an individual who had ceased chelation therapy after a history of repeated red‐cell transfusions. The management of thalassemia using modern chelation regimes is discussed.

Patients with blood transfusion-dependent anemias develop transfusional iron overload (TIO), which may cause cardiosiderosis. In patients with an ineffective erythropoiesis, such as thalassemia major, common transfusion regimes aim at suppression of erythropoiesis and of enteral iron loading. Recent data suggest that maintaining residual, ineffective erythropoiesis may protect from cardiosiderosis. We investigated the common consequences of TIO, including cardiosiderosis, in a minipig model of iron overload with normal erythropoiesis. TIO was mimicked by long-term, weekly iron-dextran injections. Iron-dextran loading for around one year induced very high liver iron concentrations, but extrahepatic iron loading, and iron-induced toxicities were mild and did not include fibrosis. Iron deposits were primarily in reticuloendothelial cells, and parenchymal cardiac iron loading was mild. Compared to non-thalassemic patients with TIO, comparable cardiosiderosis in minipigs required about 4-fold greater body iron loads. It is suggested that this resistance against extrahepatic iron loading and toxicity in minipigs may at least in part be explained by a protective effect of the normal erythropoiesis, and additionally by a larger total iron storage capacity of RES than in patients with TIO. Parenteral iron-dextran loading of minipigs is a promising and feasible large-animal model of iron overload, that may mimic TIO in non-thalassemic patients.

Objective: To evaluate gynaecological features of a group of transfusion dependent beta-thalassemic women and to analyze their re- productive function with the morpho-functional features of genital female tract. Materials and Methods: Cross-sectional study in a Uni- versity Hospital and Tertiary Care Center. Fifty-nine transfusion-dependent beta-thalassemic women in reproductive age, were divided into two groups: to group A were assigned women with spontaneous menarche (n=44), while to group B were allocated patients with inducted menarche. Data on demographic characteristics, iron overload in liver and heart (evaluated with T2∗ RMN method), chelation therapy, and reproductive function were collected. Difference in demographic characteristics, chelation therapy, iron status, and repro- ductive function between groups were assessed, together with correlation analysis of iron overload. Results: Patients in group B had a worse reproductive function and a higher myocardial iron overload, than patients in group A. Moreover multivariate logistic regression showed a significant correlation between uterine biometry, FSH, E2, parity and hearth iron T2∗HSIV, but not with liver iron. Conclu- sion: The present data shows that myocardial iron loading could be putative of prolonged and severe iron overload in the female geni- tal tract, impairing fertility and reproductive function in patients affected with beta-thalassemia major under chelation therapy.

Aim: To investigate iron loading within the liver, pancreas, spleen, and bone marrow using magnetic resonance imaging (MRI) transverse relaxation rate (R2*), in patients with diffuse liver diseases; to evaluate the relationships between iron accumulation in these tissue compartments; and to assess the association between tissue iron overload and the pattern of hepatic cellular iron distribution (hepatocytes versus Kupffer cells). Material and methods: Fifty-six patients with diffuse liver diseases had MRI-derived R2* values, using a multi-echo chemical-shift encoded MRI sequence, of the liver, pancreas, spleen, and vertebral bone marrow. All patients had liver biopsy samples scored for hepatic iron grading (0–4) and iron cellular distribution (within hepatocytes only or within both hepatocytes and Kupffer cells). Results: Liver R2* increased with histological iron grade (RS=0.58, p

Background Paroxysmal atrial tachyarrhythmias frequently occur in beta-thalassemia major (beta-TM) patients. The aim of the current study was to evaluate the atrial electromechanical delay (AEMD) in a large beta-TM population with normal cardiac function and its relationship to atrial fibrillation (AF) onset.Methods Eighty beta-TM patients ( 44 men, 36 women), with a mean age of 36.2 +/- 11.1 years, and 80 healthy subjects used as controls, matched for age and gender, were studied for the occurrence of AF during a 5-year follow-up, through 30-day external loop recorder (ELR) monitoring performed every 6 months. Intra-AEMD and inter-AEMD of both atria were measured through tissue Doppler echocardiography. P-wave dispersion (PD) was carefully measured using 12-lead electrocardiogram ( ECG).Results Compared to the healthy control group, the beta-TM patients showed a statistically significant increase in inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD. Dividing the beta-TM group into two subgroups (patients with or without AF), the inter-AEMD, intra-left AEMD, maximum P-wave duration, and PD were significantly higher in the subgroup with AF compared to the subgroup without AF. There were significant good correlations of intra-left AEMD and inter-AEMD with PD. A cut-off value of 40.1 ms for intra-left AEMD had a sensitivity of 76.2% and a specificity of 97.5% in identifying beta-TM patients with AF risk. A cut-off value of 44.8 ms for inter-AEMD had a sensitivity of 81.2% and a specificity of 98.7% in identifying this category of patients.Conclusions Our results showed that the echocardiographic atrial electromechanical delay indices (intra-left and inter-AEMD) and the PD were significantly increased in beta-TM subjects with normal cardiac function. PD and AEMD represent non-invasive, inexpensive, useful, and simple parameters to assess the AF risk in beta-TM patients.

Uzun, Feyzahan/0000-0002-3050-0714; akin, mehmet/0000-0002-3086-3988 WOS: 000416982700004 PubMed: 29234223 Purpose: To measure the retinal nerve fiber layer thickness (RNFLT) in children with beta-thalassemia major and to compare with healthy controls. Methods: A total of 47 patients with b-thalassemia major and 51 healthy controls were included. Each subject underwent a standard ophthalmological examination. RNFLT measurements were performed using optical coherence tomography. Results: Mean age of the patient group and healthy controls were 13.7 +/- 2.1 and 14.3 +/- 2.2 years, respectively. Mean peripapillary RNFL thickness was 94 mu m in the patient group, and 100 mu m in the control group (p < 0.01). in patients with b-thalassemia major, RNFL was thinner in all quadrants than control subjects. Within the beta-thalassemia major group neither average RNFLT nor each four quadrant RNFLT were correlated with the age, serum ferritin or serum hemoglobin levels (p > 0.05). Conclusion: in this study, we observed RNFL was thinner in patients with beta-thalassemia major. Thinning of RNFL did not correlate with hemoglobin or ferritin levels.

OBJECTIVE Beta-thalassemia major (TM) is a genetic hemoglobin disorder causing chronic hemolytic anemia. Since cardiac insufficiency and arrhythmias are the primary causes of mortality in such patients, monitoring of cardiac iron load is important in management of the disorder. The purpose of this study was to investigate the importance of fragmented QRS (fQRS) and its relation to the cardiac T2* value for the evaluation of cardiac iron load in TM patients. METHODS This retrospective study included 103 TM patients. The patients' T2* values, measured by cardiac MRI and 12-lead surface ECGs, were interpreted. The cardiac T2* values under 20 were considered as cardiac iron overload. The relationship between the cardiac T2* value and fQRS in ECG was investigated. RESULTS The median age of the patients was 22.6 ± 6.6 years. All patients were on regular blood transfusions and iron chelators. The patients had no risk factors for coronary artery disease. In 50 (48%) patients fQRS was detected, and in 37 (74%) of these the T2* values were low. 86% of patients with cardiac involvement (37) had fQRS, but 22% of patients with non-involvement (13) had fQRS (p < 0.001). CONCLUSION Since cardiac involvement is the primary cause of mortality in TM patients, the early diagnosis of cardiac dysfunction is of vital importance. The search for fQRS in the ECGs of these patients, particularly when cardiac T2* values cannot be determined and followed, is a non-expensive and easy-to-attain method for therapy management.

Background: Patients with beta-thalassemia major are categorized as high risk for cardiovascular complications due to myocardial iron overload that leads to reduce both systolic and diastolic function as well as cardiac arrhythmias. The present study aimed to assess the relationship between the presence of fragmented QRS and iron overload determined by magnetic resonance imaging (MRI) T2* in patients with beta-thalassemia major. Materials and Methods: This cross-sectional study was performed on 71 consecutive patients with beta-thalassemia major that referred to Shahid Rajaei Heart Center in 2014 for assessing myocardial T2* using cardiac MRI. The cardiac MR T2* values and electrocardiograms (ECGs) of the patients were evaluated. The patients' 12-lead surface ECGs were analyzed for the presence of fragmented QRS. Results: The presence of fragmented QRS was revealed in 19.7% of patients. The study showed the presence of a significant relationship between cardiac T2* value and fragmented QRS in ECG that the mean myocardial T2* in those with and without fragmented QRS was 11.46 ± 6.63 and 21.72 ± 9.49 (P < 0.001). Using the multivariable linear regression model, it was shown a significant association between the presence of fragmented QRS and myocardial T2* value (standardized beta = −0.318, P = 0.007). In those with fragmented QRS, a significant association was found between myocardial and liver T2* values [r = 0.677, P = 0.008. Conclusion: A notable number of patients with beta-thalassemia major have fragmented QRS pattern in ECGs that is accompanied with lowering myocardial T2* value in these patients.

Background: The ideal management of thalassemia involves a multidisciplinary therapeutic team approach and should be preferably done at a comprehensive thalassemia care center with all sorts of specialists and the backup of a well-equipped blood bank. However, in developing country like ours, these facilities are not available in rural set up. So, a situation where conservative therapy with regular blood transfusion is the only choice left to innumerable thalassemic children. Objective: To evaluate the existing conservative management protocol of Beta-thalassemia major patients in the setup of a subdivision level Government Hospital of rural West Bengal, India. Materials and Methods: The study was performed between December 2009 and December 2011. Beta-thalassemia major patients, registered in blood bank for moderate transfusion regimen, were taken in study. All the patients were screened for Transfusion Transmittable Infections at the time of registration and thereafter periodically every six months. Iron chelation therapy was given simultaneously with transfusion at a dose of 20 to 40 mg/kg/day for six days. The patients were advised to follow up with chelation therapy at home by daily infusion with a goal of maintaining serum ferritin level below 1000 ng/ml. Over this long period of study, the patients were periodically evaluated for complications. Results: The average blood requirement (ml/kg/year) in 1-5 years, 6-10 years, and 11-15 years were 110, 150, and 180, respectively. Incidence of Hepatitis C Virus infection in 1-5 years and 6-10 years were 1.75% and 2.08%, respectively. It is well seen that serum ferritin level increase with ascending age as does the blood consumption. Conclusion: Conservative management may be the best alternative and at times the only hope for patients in developing country like ours. However, in order to decrease the disease load, steps need to be taken to introduce preventive measures.

Background Excessive iron accumulation in the visceral organs creates problems for patients with beta-thalassemia major. Despite chelation therapy, mortality rate from the complications of this disease is still quite high. Objectives This study aimed to investigate the effectiveness of nutrition, exercise, and a praying program at reducing iron overload in patients with beta-thalassemia major. Patients and methods This randomized clinical trial assessed the effect of the designed care program on iron overload. The study was conducted in 38 patients with beta-thalassemia major who ranged in age from 15 - 35 years and had been referred to the largest center for thalassemic patients in Shiraz. The patients were randomly assigned to an intervention (n = 18) and a control (n = 20) group. Blood samples were collected from the participants before and two months after the intervention. Then, the data were statistically analyzed using chi-square, Fisher's exact test, Mann-Whitney U-test, Wilcoxon, independent samples t-test, and paired samples t-test. Results The results showed that the mean level of serum ferritin significantly decreased in the intervention group two months after beginning the intervention. Also, the mean level of serum iron decreased in the intervention group, but the difference was not statistically significant. Conclusions The planned educational program could be used to reduce iron overload and ultimately improve the patients' health status.

BACKGROUND: Myocardial black blood (BB) T2* relaxometry at 1.5T provides robust, reproducible and calibrated non-invasive assessment of cardiac iron burden. In vitro data has shown that like T2*, novel native Modified Look-Locker Inversion recovery (MOLLI) T1 shortens with increasing tissue iron. The relative merits of T1 and T2* are largely unexplored. We compared the established 1.5T BB T2* technique against native T1 values at 1.5T and 3T in iron overload patients and in normal volunteers. METHODS: A total of 73 subjects (42 male) were recruited, comprising 20 healthy volunteers (controls) and 53 patients (thalassemia major 22, sickle cell disease 9, hereditary hemochromatosis 9, other iron overload conditions 13). Single mid-ventricular short axis slices were acquired for BB T2* at 1.5T and MOLLI T1 quantification at 1.5T and 3T. RESULTS: In healthy volunteers, median T1 was 1014 ms (full range 939-1059 ms) at 1.5T and modestly increased to 1165ms (full range 1056-1224 ms) at 3T. All patients with significant cardiac iron overload (1.5T T2* values

Background Thyroid gland dysfunction and echocardiographic cardiac abnormalities are well-documented in patients with transfusion dependent beta-thalassemia major (β-TM). Aim This cross-sectional analytic study was conducted to investigate left ventricle (LV) diastolic and systolic function using pulsed Doppler (PD) and tissue Doppler (TD) echocardiography and correlate that with serum level thyroid stimulating hormone in patients with β-TM. Methods The study was conducted on patients with β-TM (n = 110, age 15.9 ± 8.9 years) and compared with a control group (n = 109, age 15.8 ± 8.9 years). In all participants, echocardiographic indices of PD and TD were performed and blood samples were withdrawn for measuring the serum level of TSH, free T4, and ferritin. A linear regression analysis was performed on TSH level as the dependent variable and serum ferritin as independent. Stepwise multiple regression analysis was used to determine the odds ratio of different biochemical and echo variables on the risk of developing hypothyroidism. Results Patients with β-TM compared with controls had thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm/M2, P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm/m2, P < 0.01) and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm/m2, P < 0.001). In addition, β-TM patients had higher transmitral E wave velocity (E) (70.81 ± 10.13 vs. 57.53 ± 10.13 cm/s, P = 0.02) and E/A ratio (1.54 ± 0.18 vs. 1.23 ± 0.17, P < 0.01) and shorter deceleration time (DT) (170.53 ± 13.3 vs. 210.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em) was significantly higher in the β-TM group (19.68 ± 2.81 vs. 13.86 ± 1.41, P < 0.05). The tissue Doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in the β-TM group compared with controls with Sm, 4.82 ± 1.2 vs. 6.22 ± 2.1 mm/sec, P < 0.05 and (Em), 3.51 ± 2.7 vs. 4.12 ± 2.5 mm/sec. P < 0.05, respectively). The tricuspid valve velocity was significantly higher in β-TM patients compared with controls 2.85 ± 0.56 vs. 1.743 ± 0.47 m sec, respectively, P < 0.01). The prevalence of subclinical hypothyroidism in patients with β-TM was 15.4%, with significantly higher mean serum TSH compared with controls (6.78 ± 1.5 vs. 3.10 ± 1.02 μIU/mL, P < 0.01) and positively correlated with the serum ferritin level ( r = 0.34, P = 0.014). On multiple regression analysis, the LV mass, LVEF%, and E/A ratio were not positive predictors of hypothyroidism in patients with β-TM. Conclusion We conclude that patients with β-TM had a high prevalence of subclinical hypothyroidism of 15.4%. Thyroid stimulating hormone was significantly high and positively correlated with the serum ferritin level. Echo cardiographic pulsed Doppler showed a restrictive LV diastolic pattern suggestive of severe diastolic dysfunction with preserved left ventricle systolic function.

Objective: It was studied the clinical management and the medical outcomes of 6 pregnancies in 5 women affected by Beta Thalassemia major, based on last guidelines and pharmacological treatments. Background: Paediatric Department and Department of Obstetrics and Gynaecology of the University of Catania. Methods: These patients were taken among a group of 116 women affected by beta-thalassemia major divided into three subgroups, according to the characteristics of their menstrual cycle: 1) women with primitive amenorrhoea, 2) women with secondary amenorrhoea and 3) women with normal menstruation. Only one woman, affected by primitive amenorrhoea, needed the induction of ovulation. An accurate and detailed pre-pregnancy assessment was effected before each conception. This was constituted by a series of essays, including checks for diabetes and hypothyroidism, for B and C hepatitis and for blood group antibodies. Moreover were evaluated: cardiac function, rubella immunity and transaminases. Other pregnancy monitoring, and cares during labour and delivery were effected according to usual obstetrics practice. Results: All the women were in labour when they were 38 week pregnant, and the outcome were six healthy babies born at term. There were no complications related to the pregnancy and to the immediate outcome after delivery. Conclusions: The improvements of current treatments, especially in the management of iron deposits, the prolongation of survival rate, will result in a continuous increase of pregnancies in thalassemic women. Pregnancy is now a real possibility for women affected by such disease. Although numerous complications can occur, vigilant monitoring by both experienced obstetricians and hematologists can lead to successful pregnancy outcomes (Tab. 1, Fig. 1, Ref. 16). Full Text in PDF www.elis.sk.

WOS: 000286902400010, PubMed ID: 21071497, Background The efficacy of cardiac iron chelation in transfusion-dependent patients has been demonstrated in one-year prospective trials. Since normalization of cardiac T2* takes several years, the efficacy and safety of deferasirox was assessed for two years in patients with beta-thalassemia major in the cardiac sub-study of the EPIC trial. Design and Methods Eligible patients with myocardial T2* greater than 5 to less than 20 ms received deferasirox, with the primary endpoint being the change in T2* from baseline to two years. Results Baseline myocardial T2* was severe (>5 to = 5%) increased serum creatinine, rash and increased alanine aminotransferase. Conclusions Continuous treatment with deferasirox for two years with a target dose of 40 mg/kg/d continued to remove iron from the heart in patients with beta-thalassemia major and mild, moderate and severe cardiac siderosis. (Clinicaltrials.gov identifier: NCT 00171821), Novartis Pharma AG; British Heart FoundationBritish Heart Foundation [PG/09/074/27961]; National Institute for Health ResearchNational Institute for Health Research (NIHR) [NF-SI-0508-10081], this study was sponsored by Novartis Pharma AG. Financial support for medical editorial assistance was provided by Novartis Pharmaceuticals.

Background : Children suffering from beta-thalassemia major require repeated blood transfusions which may be associated with dangers like iron overload and contraction of infections such as HIV, HCV, and HBsAg which ultimately curtail their life span. On the other hand, inadequate transfusions lead to severe anemia and general fatigue and debility. Materials and Methods: Data were obtained from 142 beta-thalassemia major patients aged 3 years or more receiving regular blood transfusions at a transfusion centre in Western India from 1 April 2009 to 30 June 2009. The clinical data and laboratory results were subsequently analyzed. Results: Of the 142 patients, 76 (53.5%) were undertransfused (mean Hb Conclusions: The study suggests the need to step up the transfusions to achieve hemoglobin goal of 10 gm% (as per the moderate transfusion regimen) and also to institute urgent and effective chelation measures with the aim of keeping serum ferritin levels below 1000 ng/ml to avoid the systemic effects of iron overload. In addition, strict monitoring of the children for endocrinopathy and other systemic effects of iron overload should be done. Rigid implementation of quality control measures for the ELISA kits used to detect HCV in donor blood needs to be done urgently. Alternately, more sensitive and specific measures (like NAT testing) should be employed for detection of HCV. In the absence of a definitive cure accessible and available to all patients, strict implementation of the above suggested measures will go a long way in improving the quality (and quantity) of life in patients of beta-thalassemia major.

BackgroundDoppler echocardiographic studies in patients with β-Thalassemia Major (β-TM) had shown different patterns of left ventricle (LV) systolic and diastolic dysfunctions.AimThis cross-sectional study was designed to study the LV systolic and diastolic function in patients with β-TM using Pulsed Doppler (PD) Echocardiogram and assess the QTc interval and QT dispersion (QTd) on 12 leads ECG.MethodAll patients were evaluated clinically as well as by echocardiography and 12 leads ECG. The study included patients with β-TM (n = 38, age 15.7 ± 8.9 years), compared with an age-matched healthy control group (n = 38, age 15.9 ± 8.9 years).ResultsIn 38 patients with β-TM Compared with healthy control group, The QTc interval and the QTd dispersion on ECG were increased with no significant difference mode echo showed that β-TM patients have thicker LV septal wall index (0.659 ± 0.23 vs. 0.446 ± 0.219 cm/M2, P < 0.001), posterior wall index (0.659 ± 0.235 vs. 0.437 ± 0.214 cm/M2, P < 0.01), and larger LVEDD index is (3.99 ± 0.48 vs. 2.170 ± 0.57 cm/M2. P < 0.05). Pulsed Doppler showed high LV trans-mitral E wave velocity index (70.818 ± 10.139 vs. 57.532 ± 10.139, P < 0.05) and E/A ratio (1.54 vs.1.23, P < 0.01). The duration of deceleration time index (DT) and isovolumic relaxation time index (IVRT) were significantly shorter in patients with β-TM (150.234 ± 20.0.23 vs. 167.123 ± 167.123 ± 19.143 msec/M2, P < 0.01) and (60.647 ± 6.77 vs. 75.474 ± 5.83 msec/M2, P < 0.001), respectively. The tricuspid valve velocity in patients with β-TM was significantly higher than controls (2.993 ± 0.569 vs. 1.93 ± 0.471 m/sec, respectively, P < 0.01), with calculated pulmonary artery pressure of 2.4 times the control (36.0 vs. 14.8 mmHg). However, the LVEF% or fractional shortening were not significantly different.ConclusionIn this study, β-thalassemia major patients compared with controls have differences of QT dispersion and corrected QT interval that is of no statistical significance. A significantly thicker LV wall and LV diastolic filling indices are suggestive of restrictive diastolic pattern. These data indicate that LV diastolic abnormalities compromised initially in patients with β-thalassemia major.

Background: Despite recent progress in iron chelation therapy, sudden cardiac death due to malignant ventricular arrhythmias remains a vexing, clinical problem in patients with β-thalassemia major (TM). In this study we assessed whether the major indices of QT variability, emerging tools for risk stratification of sudden cardiac death, differ in young asymptomatic patients with TM and healthy persons. Methods: Thirty patients with TM and 30 healthy control subjects underwent a 5-min electrocardiography recording to calculate the following variables: QT variance (QTv), QTv normalized for mean QT (QTVN) and QT variability index (QTVI). All subjects also underwent a two-dimensional and Doppler echocardiography study and magnetic resonance imaging (MRI) to determine cardiac and hepatic T2* values. Results: No differences were observed in clinical and conventional echo-Doppler findings in healthy control subjects and patients with TM whereas QTv, QTVN and QTVI values were significantly higher in patients than those in controls (QTv, P

Thirty-seven patients with beta-thalassemia major, including 14 adolescents (15.2 +/- 3.0 years) and 23 adults (26.4 +/- 6.9 years), were studied. T2 relaxation time (T2) of the liver, bone marrow, pancreas and pituitary gland was measured in a 1.5-Tesla magnetic resonance (MR) imager, using a multiecho spin-echo sequence (TR/TE 2,000/20, 40, 60, 80, 100, 120, 140, 160 ms). Pituitary gland height was evaluated in a midline sagittal scan of a spin-echo sequence (TR/TE, 500/20 ms). The T2 of the pituitary gland was higher in adolescents (59.4 +/- 15 ms) than in adults (45.3 +/- 10.4 ms), P < 0.05. The T2 of the pancreas was lower in adolescents (43.6 +/- 10.3 ms) than in adults (54.4 +/- 10.4 ms). No difference among groups was found in the T2 of the liver and bone marrow. There was no significant correlation of the T2 among the liver, pancreas, pituitary gland and bone marrow. There was no significant correlation between serum ferritin and T2 of the liver, pancreas and bone marrow. Pituitary T2 showed a significant correlation with pituitary gland height (adolescents: R=0.63, adults: R=0.62, P < 0.05) and serum ferritin (adolescents: R=-0.60, adults: R=-0.50, P < 0.05). In conclusion, iron overload evaluated by T2 is organ specific. After adolescence, age-related T2 changes are predominantly associated with pituitary siderosis and fatty degeneration of the pancreas. Pituitary size decreases with progressing siderosis. European Radiology

Aims: The aim of this study was to assess ocular changes in thalassemia patients who have received multiple transfusions and chelate binding therapy in order to avoid iron accumulation. Settings and Design: A cross-sectional study. Subjects and Methods: A total of 54 thalassemia major patients were selected as case group, and 54 age- and sex-matched healthy subjects were regarded as a control group. Ocular examination included visual acuity, refraction testing, slit lamp examination, funduscopy, tonometry, perimetry, tear break-up time test, and color vision testing were performed for all the participants. We computed the frequency and duration of blood transfusion, the mean serum ferritin level, pretransfusion hemoglobin concentration, and type, duration, and daily dose of chelation therapy for thalassemia patients based on their records. Statistical Analysis Used: All data analysis was performed using SPSS, version 19. Results: All the thalassemic patients were asymptomatic, but abnormal ocular findings (dry eye (33.3%), cataract (10.2%), retinal pigment epithelium degeneration (16.7%), color vision deficiency (3.7%), and visual field defects (33.7%)) were seen in 68.5% of thalassemic group. The prevalence of ocular abnormalities in normal group was 19.4%, which was significantly lower than that in thalassemia patients (P = 0.000). No significant correlation was found between ocular abnormalities and mean serum ferritin level (P = 0.627) and mean hemoglobin concentration (P = 0.143). Correlation of number of blood transfusion with the presence of ocular abnormalities was found to be statistically significant (P = 0.005). Conclusions: As life expectancy for beta-thalassemia patients extends, regular ophthalmological evaluation to detect early changes in their ocular system is recommended.

The aim of our cross-sectional study was to evaluate the effects of hormonal replacement therapy (HRT) on a population of young thalassemics in order to understand better the role of hypogonadism in the balance of bone metabolism. Markers of bone turnover and bone mineral density (BMD) were measured in 40 young patients (mean age 19.8 +/- 4.5 years) with beta-thalassemia major: 20 subjects were biochemically eugonadal. since they were undergoing HRT (group A, treated patients), and 20 were hypogonadic, having suspended HRT (group B, untreated patients). We also examined 20 healthy control subjects (group C) matched for age, anthropometric features and sex to the study groups. Our study shows that young thalassemic patients exhibit a significant loss of cortical and trabecular bone [aBMD L2-L4: 0.886 +/- 0.052 g/cm2 (group A), 0.726 +/- 0.040 g/cm2 (group B), 1.083 +/- 0.090 g/cm (group C); aBMD femoral neck: 0.890 +/- 0.071 g/cm2 (group A), 0.700 +/- 0.065 g/cm2 (group B), 0.934 +/- 0.076 g/ cm2 (group C)]. Osteoporosis is only observed at the lumbar level in treated thalassemic patients, while in untreated patients it involves the femoral neck also. Bone turnover in thalassemic patients is higher in the resorptive phase, than in the neoformation phase and this is more marked in hypogonadic untreated patients. In conclusion, our data demonstrate the important role played by hypogonadism in the development and deterioration of osteopenia/osteoporosis in thalassemia major. Consequently, sex hormone replacement therapy represents an appropriate tool in the prevention and treatment of osteoporosis in thalassemics, probably together with bisphosphonates in cases with severely increased bone resorption.

34th Annual Meeting of the European-Paediatric-Nephrology-Congress -- JUN 18-20, 2000 -- HELSINKI, FINLAND WOS: 000090145800027 PubMed ID: 11095025 In patients with beta -thalassemia major, the most important cause of mortality and morbidity is organ failure due to deposits of iron.. In this study, the nature of the kidney injury and possible pathogenetic factors were investigated. Seventy children with beta -thalassemia major and 14 age and sex-matched healthy children were involved in the study. Blood and timed urine samples were obtained for hematological and biochemical tests. The mean values of blood urea nitrogen (BUN), serum creatinine, creatinine clearance, serum sodium, urine osmolality, fractional excretion of sodium, potassium, and uric acid were not statistically different between the groups. Serum levels of potassium, phosphorus, and uric acid and the urine volume, high urinary protein to creatinine (U-P/Cr), urinary N-acetyl-beta -D-glucosaminidase to creatinine (U-NAG/Cr), and urinary malondialdehyde to creatinine, (U-MDA/Cr), and the tubular phosphate reabsorption (TRP) values were statistically different between two groups (P

Twenty-one patients with homozygous b-TM and Increased frequency of venous thrombosis, re13 healthy controls were investigated. Mean age current transient ischemic attacks, and stroke for b-TM patients (8 women, 12 men) was 11.5 has been documented in patients with beta(4–21) and for control group (6 women, 7 men) thalassemia major (b-TM) [1,2] and shown to rep11.6 (7–20). Routine hematological measurements resent an important cause of mortality [3]. In this were performed in control subjects and patients context the pathophysiologic role of platelets has with standard techniques. All patients had plasma been supported by Eldor et al. who reported deferritin levels .1500 g/L (normal levels of 50 to crease of platelet life span and more recently in150 g/L). The mean hemoglobin level was 9.2 g/dL creased urinary excretion of TxA2 metabolites [4]. and mean hematocrit level was 27.1%. Patients The mechanism of increased platelet activation in discontinued any therapy 4 weeks before the study, b-TM patients is still unclear, but it could be associand their last blood transfusion was at least 8 weeks ated with red blood cell (RBC) abnormality. In fact, before the study began. No patient had a clinical RBCs affect platelet activation [5,6], but it has never history of thrombosis. established whether the release of hemoglobin by RBCs might also play a role. Hb in the nanomolar 1.2. Materials range is able to favor platelet activation by redox cycling of heme-bound iron or heme-derived iron Collagen, ADP, Thrombin, ATP standard solution, [7]. Since large amounts of Hb, non-Hb-iron, and and luciferin-luciferase were obtained from Chronoferritin were documented in thalassemic patients Log, catalase (CAT) from Calbiochem (La Jolla, [8,9], we investigated if an iron-mediated mechaCA), desferroxamine (DSF) from Sigma (St. Louis, MO). nism contributes to the increase platelet activation in b-TM patients. 1.3. Platelet Activation Study

The health background management and outcomes of 5 pregnancies in 4 women affected by Cooley Disease, from Paediatric Institute of Catania University, are described, considering the preconceptual guidances and cares for such patients. These patients were selected among a group of 100 thalassemic women divided into three subgroups, according to their first and successive menstruation characteristics: i) patients with primitive amenorrhoea, ii) patients with secondary amenor-rhoea and iii) patients with normal menstruation. Only one woman, affected by primitive amenorrhoea, needed the induction of ovulation. A precise and detailed prepregnancy assessment was effected before each conception. This was constituted by a series of essays, including checks for diabetes and hypothyroidism, for B and C hepatitis and for blood group antibodies. Moreover were evaluated: cardiac function, rubella immunity and transaminases. Other pregnancy monitoring, and cares during labour and delivery were effected according to usual obstetrics practice. All the women were in labour when she were 38 week pregnant, and the outcome were five healthy babies born at term, weighting between 2600 and 3200gs. The only complication was the Caesarean section. The improvements of current treatments, especially in the management of iron deposits, the prolongation of survival rate, will result in a continuous increase of pregnancies in thalassemic women. Pregnancy is now a real possibility for women affected by such disease. We are furthermore studying the possibility to collect the fetus' umbilical cord blood, after the delivery, to attempt eterologus transplantation to his mother trying to get a complete marrow reconstitution., peer-reviewed

In order to clarify whether the damage in gonadotropin secretion due to iron overload in patients with beta-thalassemia is of pituitary or hypothalamic origin, 14 euthyroid patients (8 females and 6 males, age 15-24 years) affected by beta-thalassemia major with hypogonadotropic hypogonadism were studied. Luteinizing-hormone (LH), follicle-stimulating hormone (FSH) and free alpha-subunit (FAS) were measured during LH-releasing hormone (LH-RH) stimulation test, and thyroid-stimulating hormone (TSH), prolactin (PRL) and FAS during thyrotropin-releasing hormone (TRH) stimulation test. During LH-RH stimulation, the mean basal LH, FSH and FAS levels were similar to those found in normal prepubertal children, but the peak values were lower than those found in such children. Also during TRH stimulation, the mean peak values of FAS were lower than those of normal prepubertal children, but the TSH response was normal. The lack of response of gonadotropins and FAS to LH-RH cannot exclude hypothalamic failure; however, the normal response of TSH to TRH, in spite of the poor response of FAS, indicates that the origin of hypogonadotropic hypogonadism is the pituitary damage concerning not only the gonadotroph but also the thyrotroph cells.

Background Doppler echocardiographic studies of the left ventricle (LV) function in patients with β-Thalassemia Major (β-TM) had shown different patterns of systolic and diastolic dysfunctions associated with abnormal serum brain natriuretic peptide (BNP). Aim This cross-sectional study was designed to study the LV systolic and diastolic functions and correlate that with serum level of N-terminal pro brain natriuretic hormone (NT- pro BNP) in patients with β-TM using Pulsed Doppler (PD) and Tissue Doppler (TD) echocardiography. Methods The study was conducted on patients with β-TM (n = 38, age 15.7 ± 8.9 years) and compared with an age-matched controls (n = 38, age 15.9 ± 8.9 years). In all participants, PD and TD echocardiography were performed and blood samples were withdrawn for measuring the serum level of NT-pro BNP, ferritin, and alanine transaminase. Results Patients with β-TM compared with controls, have thicker LV septal wall index (0.65 ± 0.26 vs. 0.44 ± 0.21 cm, P < 0.001), posterior wall index (0.65 ± 0.23 vs. 0.43 ± 0.21 cm, P < 0.01), and larger LVEDD index (4.35 ± 0.69 vs.3.88 ± 0.153 mm, P < 0.001). In addition, β-TM patients have higher transmitral E wave velocity (E) (70.818 ± 10.139 vs. 57.532 ± 10.139, p = 0.027) and E/A ratio (1.54 ± 0.17 vs. 1.23 ± 0.19, P < 0.01) and shorter deceleration time (DT) (160.13 ± 13.3 vs. 170.50 ± 19.20 m sec, P < 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em–) was significantly higher in β-TM group (19.6 ± 2.81 vs. 13.868 ± 1.41, P < 0.05). The tissue doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in β-TM group compared to controls (Sm: 4.82 ± 1.2 vs. 6.22 ± 2.1 mm/sec, P < 0.05; Em: 3.51 ± 2.7 vs. 4.12 ± 2.5 mm/sec P < 0.05, respectively). The tricuspid valve velocity was significantly higher in β-TM patients compared with controls (2.993 ± 0.569 vs. 1.93 ± 0.471 m/sec, respectively, P < 0.01). The mean serum NT pro-BNP in β-TM was significantly higher compared with controls (37.6 ± 14.73 vs. 5.5 ± 5.4pg/ml, P < 0.05). The left ventricle ejection fraction (EF%) and fractional shortening (FS%) were not significantly different between both groups. Conclusion We conclude that patients with β-TM had a significantly higher serum level of NT-pro BNP that is positively correlated with the E/Em ratio on tissue Doppler. Furthermore, we confirm our previous findings that patients with β-TM exhibit LV diastolic pattern on echocardiogram suggestive of restrictive type with well preserved left ventricle systolic function.