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The thalassaemia syndromes (TS) show different phenotype severity. Developing a reliable, practical and global tool to determine disease severity and tailor treatment would be of great value. Overall, 7910 patients were analysed with the aim of constructing a complication risk score (CoRS) to evaluate the probability of developing one or more complications. Nine independent variables were included in the investigation as predictors. Logistic regression models were used for Group A [transfusion-dependent thalassaemia (TDT)], Group B [transfused non-TDT (NTDT)] and Group C (non-transfused NTDT). Statistically significant predictors included age (years), haemoglobin levels, hepatic transaminases [alanine aminotransferase (ALT) and aspartate aminotransferase] and left-ventricular ejection fraction (LVEF) for Group A; age (years), age at first chelation (months), ALT and LVEF for Group B; and age (years), mean serum ferritin (SF) levels and LVEF for Group C. The area under the receiver operating characteristic curve was 84·5%, 82·1% and 80·0% for Groups A, Group B and Group C respectively, suggesting the models had good discrimination. Finally, the CoRS for each group was categorised into four risk classes (low, intermediate, high, and very high) using the centiles of its distribution. In conclusion, we have developed a CoRS for TS that can assist physicians in prospectively tailoring patients’ treatment.

Background Hydroxyurea (hydroxycarbamide) promotes the production of foetal haemoglobin (HbF) by reactivating gamma-genes. Evidence has shown clinical benefits of hydroxyurea in people with sickle cell anemia; however, only a few studies have assessed this treatment in people with beta (β)-thalassaemia. Objectives The primary objective is to review the efficacy of hydroxyurea in reducing or ameliorating the requirement of blood transfusions in people with transfusion-dependent β-thalassaemia. The second objective is to review the safety of hydroxyurea with regards to severe adverse effects in this population. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and hand searching of journals and conference abstract books. We also searched electronic databases and trial registries, including ClinicalTrials.gov, the WHO ICTRP and PubMed (09 October 2018).Date of last search of the Group's haemoglobinopathies trials register: 04 March 2019. Selection criteria Randomised controlled trials of hydroxyurea in people with transfusion-dependent β-thalassaemia, compared with placebo or standard treatment or comparing different doses of hydroxyurea. Data collection and analysis Two authors independently assessed trials for inclusion in the review, which was verified by a third author. Main results No trials were eligible for inclusion in this review. Authors' conclusions Currently, there is no high-quality evidence to support or challenge the continued use of hydroxyurea for managing people with transfusion-dependent β-thalassaemia. Multicentre, randomised controlled trials (compared to placebo or other available treatment, i.e. blood transfusion and iron chelation) are needed in order to assess the efficacy and safety of hydroxyurea for reducing the need for blood transfusion, for maintaining or improving mean haemoglobin levels, as well as for determining its cost-effectiveness.

β-Thalassemia is the most common hereditary disorder characterized by reduced production of β-globin chains of hemoglobin A (HbA). In recent years, hydroxyurea (HU) has shown promising therapeutic benefits in patients with β-thalassemia by fetal hemoglobin augmentation. We have analyzed effects of hydroxyurea treatment on oxidative stress in β-thalassemia patients by assessing activities of paraoxonase (PON) and arylesterase along with malondialdehyde (MDA) and total reactive oxygen species (ROS) concentrations. Blood samples from 159 individuals including 56 HU-treated and 58 untreated β-thalassemia patients and 45 healthy controls were analyzed. PON activity was found to be highest in healthy individuals (177.76 ± 4.44 U/mL) as compared to treated (52.67 ± 3.65 U/mL) and untreated (55.11 ± 3.26 U/mL) patients. A similar trend was observed in the case of arylesterase activity in normal, β-thalassemia-treated, and untreated (210.0 ± 11.25 U/mL, 163.03 ± 9.04 U/mL, 139.77 ± 10.10 U/mL) subjects. Serum MDA concentrations (2.59 ± 0.09 nmol/mL, 2.45 ± 0.08 nmol/mL, and 1.15 ± 0.05 nmol/mL) and total ROS concentrations (3.73 ± 0.20 nmol/mL, 3.54 ± 0.23 nmol/mL, and 2.45 ± 0.14 nmol/mL) were significantly elevated in both groups (untreated and treated) as compared to healthy individuals (P < .01). Oxidative stress was found to be markedly elevated in β-thalassemia patients as compared to healthy controls. Insignificant differences were, however, observed in mean concentrations of PON1 paraoxonase and arylesterase activities, serum MDA concentration and total ROS concentrations between HU-treated and untreated patients. We propose that HU therapy alone seems to be ineffective in managing oxidative stress and is likely to offer a better clinical outcome when supplemented with efficient iron chelation therapy and antioxidants.

SUMMARY Background In Pakistan routine blood group typing of thalassemia patients identifies ABO and Rh(D) antigens only. Therefore, other antigen incompatibilities between blood donor and blood recipient may cause alloimmunisation. Objective The aim of this study was to estimate the frequency of alloimmunisation and to evaluate the risk factors associated with its development in beta (β)-thalassemia patients receiving regular blood transfusions. Materials and Methods In total 162 β thalassemia patients were included in this study. An extended red cell antigen panel was performed to detect antibodies. Patients received red cell concentrates, which were matched for ABO and Rh(D) antigens. Clinical and laboratory data were collected and analysed to estimate the frequency of alloantibodies and the factors influencing immunisation in patients on regular blood transfusion. Results The median age of patients was 6·7 (range: 0·5–25) years. A total of 14 (8·6%) patients developed alloantibodies against red cell antigens. The most frequently occurring alloantibodies was anti-E (2·5%), anti-K (1·8%), anti-e (1·2%) and anti-D (0·6%). Five (3·1%) patients developed more than one red blood cell (RBC) alloantibody. Age at first transfusion in alloimmunised patients was 1·22 ± 0·87 years. The frequency of blood transfusion in alloimmunised patients was 23 ± 8·81 days and in those without alloimmunisation was 31·8 ± 16 days (p = 0·02). Logistic regression analysis showed no independent risk factor associated with alloimmunisation. Conclusion The frequency of transfusion was increased in patients who developed alloantibodies. Typing patients and donors to match for Rh and Kell antigens would prevent more than 90% of RBC alloantibodies and reduce the frequency of transfusion in thalassemia patients.

Background Differentiation between thalassemia major and thalassemia intermedia at presentation is not uniformly characterized, for which an absolute criteria needs to be developed. This study investigated the primary and secondary genetic modifiers to develop a laboratory finding by forming different genetic mutational combinations seen among thalassemia intermedia patients and comparing them with thalassemia major. Methods This cross-sectional study analyzed 315 thalassemia intermedia patients. One hundred and five thalassemia major patients were recruited on the basis of documented evidence of diagnosis and were receiving blood transfusion therapy regularly. Various mutational combinations were identified, and comparison was performed between thalassemia intermedia and major using statistical software STATA 11.1. Results The mean age of the total population was 5.9 ± 5.32 years of which 165 (52%) were males. Of the two groups (thalassemia intermedia and thalassemia major), IVSI-5, IVSI-1, and Fr 8-9 were more prevalent among the thalassemia intermedia cohort. When comparison was performed between the thalassemia intermedia and thalassemia major patients, it showed significant results for the presence of Xmn-1 polymorphism. Conclusion The presence of IVSI-5 homozygous with Xmn-1, IVSI-5 heterozygous with Xmn-1, Cd 30 homozygous with or without Xmn-1 and IVSI-1 homozygous or heterozygous either with or without Xmn-1 prove to be strong indicators towards diagnosis of thalassemia intermedia.

β-Thalassemia is one of the most common inherited disorders and is widely distributed throughout the world. Owing to severe deficiencies in red blood cell production, blood transfusion is required to correct anemia for normal growth and development but causes additional complications owing to iron overload. The aim of this study is to quantify the biometal dysregulations in β-thalassemia patients as compared with healthy controls. A total of 17 elements were analyzed in serum samples of β-thalassemia patients and healthy controls using ICP-MS followed by chemometric analyses. Out of these analyzed elements, 14 showed a significant difference between healthy and disease groups at p0.05 and fold change3. A PLS-DA model revealed an excellent separation with 89.8% sensitivity and 97.2% specificity and the overall accuracy of the model was 92.2%. This metallomic study revealed that there is major difference in metallomic profiling of β-thalassemia patients specifically in Co, Mn, Ni, V and Ba, whereas the fold changes in Co, Mn, V and Ba were found to be greater than that in Fe, providing evidence that, in addition to Fe, other metals are also altered significantly and therefore chelation therapy for other metals may also needed in β-thalassemia patients.