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Transfusion-dependent thalassemia (TDT) is a type of beta-thalassemia that needs regular and long-term blood transfusions. Complications can occur due to the deposition of iron in TDT patients, including endocrine complications causing deficiency of testosterone that plays a role in the secondary sexual development in males. The objective of this study was to understand the correlation between ferritin and testosterone level in male adolescences with transfusion-dependent thalassemia. This cross-sectional observational correlative study was conducted from April to August 2019 on 74 males aged 12-18 years old who were presented to the Thalassemia Outpatient clinic, Dr. Hasan Sadikin General Hospital, Bandung. Blood was collected using phlebotomy for ferritin and total testosterone serum examination. Data were then analyzed using SPSS version 17.0. Low testosterone level (

Transfusion-dependent thalassemia (TDT) patients require regular blood transfusions. The unavoidable consequence is iron overload. Iron chelation therapy is the mainstay of treatment, of which the favorable outcome depends mainly on adherence level. The aim of this study was to assess adherence to iron chelation therapy of TDT patients. A cross-sectional cohort of TDT patients were evaluated on their adherence to chelation therapy using the Thai version of Morisky Medication Adherence Scales (MMAS-8). A total of 70 patients (38 males, 32 females), with a median age of 10 years, were enrolled in the study. Sixteen patients (22.9%) and 54 patients (77.1%) were classified as high and medium-low adherence level groups. The raised serum ferritin value for 6 months previous to enrollment in the high adherence level group is lower than the medium-low adherence level group (276.4 vs. 413.0 ng/mL, p = 0.034, respectively). Factors impacted high adherence to iron chelation including younger age (p = 0.015) and deferasirox (DFX) administration (p = 0.025). The body weight and height in both groups were not statistically different. The most common obstacle to adherence was forgetfulness. The Thai version of MMAS-8 is a practical tool for evaluating adherence to chelation therapy in TDT patients. High adherence level of patients correlates with more controlled serum ferritin level. The younger age and once-daily dose chelation therapy are associated with better adherence.

Objective The objective of this study was to examine the cross-sectional convergent and known-group validity of the Malay-language EQ-5D-3L instrument in children and adults with transfusion-dependent thalassemia (TDT). Methods A cross-sectional health-related quality of life survey involving TDT patients from 12 different treatment centers across Malaysia was conducted using the Malay PedsQL 4.0 Generic Core Scales and the Malay EQ-5D-3L questionnaire. Patients with non–TDT and other hemoglobinopathies were excluded. Convergent, discriminant, and known-group validity of the EQ-5D-3L was assessed against the PedsQL 4.0 Generic Core Scales in children. In the adult population, known-group validity of the EQ-5D-3L was assessed using an a priori hypothesis between patients’ demographic characteristics and health outcomes obtained from literature. Results A total of 370 children and 225 adults were sampled. The mean (standard deviation) EQ-5D-3L scores of the children were 0.892 (0.082) and the adults were 0.887 (0.085). Convergent and discriminant validity was identified when correlated with the PedsQL domain in children. In both groups, known-group validity was evident when comparing groups of patients with reported problems to the group of patients with no reported problems on the EQ-5D-3L domains based on the a priori hypothesis derived from literature. Conclusion This study found convergent, discriminant, and known-group validity of the Malay EQ-5D-3L in a population-based sample of patients with TDT. Hence, the instrument is valid for the assessment of health-related quality of life in children and adults with TDT in Malaysia.

Objectives To assess pubertal development and its determinants in adolescents with transfusion-dependent thalassemia (TDT). Methods In this cross-sectional study from a tertiary teaching hospital in Delhi, records of adolescents aged 17-19 years with TDT on regular transfusion at thalassemia day-care centre were reviewed. Pubertal development and its determinants were assessed. Results Records of 58 (33 male) adolescents with TDT were reviewed. Among them, 42 (72.4%) had normal/delayed onset with spontaneous progression of puberty, while 16 (27.6%) had pubertal arrest/failure and received hormonal replacement therapy (HRT). Short stature was observed in all adolescents on HRT. Amongst other endocrinopathies, only hypoparathyroidism was found to be significantly higher in the HRT group. On multivariate analysis, serum ferritin (OR-1.005, 95% CI 1.002, 1.009) was observed to be the only significant determinant of pubertal arrest/failure. Conclusions A significant proportion of adolescents with TDT continue to have pubertal arrest/failure. High systemic iron load is the key determinant for this.

Background: Thalassemia is a chronic disease requiring lifelong treatment. The adherence to regular iron chelation therapy is important to ensure complication-free survival and good quality of life. The study aim to assess the adherence to iron chelation therapy (ICT) in patients with transfusion-dependent thalassemia (TDT), evaluate various causes of non-adherence and study the impact of non-adherence on the prevalence of complications secondary to iron overload. Materials and Methods: Patients with TDT on ICT for > 6 months were enrolled in the study. Hospital records were reviewed for demographic details, iron overload status, treatment details, and the prevalence of complications. A study questionnaire was used to collect information on adherence to ICT, knowledge of patients, and the possible reasons for non-adherence. Results: A total of 215 patients with a mean age of 15.07+7.68 years and an M: F ratio of 2.2:1 were included in the study. Non-adherence to ICT was found in 10.7% of patients. Serum ferritin levels were significantly higher in the non-adherent group (3129.8+1573.2 µg/l) than the adherent population (2013.1+1277.1 µg/l). Cardiac as well as severe liver iron overload was higher in the non-adherent patients. No correlation was found between disease knowledge and adherence to ICT. Difficulties in drug administration and many medicines to be taken daily were statistically significant reasons for non-adherence. There was no difference in the co-morbidities arising due to the iron overload in the two groups. Conclusion: Nearly 11% of patients with TDT were non-adherent to ICT. Non-adherence results in higher iron overload.

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Initiation of regular transfusion in transfusion-dependent thalassemia (TDT) is based on the assessment of clinical phenotype. Pathogenic HBB variants causing β-thalassemia are important determinants of phenotype and could be used to aid decision-making. We investigated the association of HBB genotype with survival in a cohort study in the four thalassemia centers in Cyprus. HBB genotype was classified as severe (β0/β0 or β+/β0), moderate (β+/β+), or mild (β0/β++ or β+/β++). Risk factors for mortality were evaluated using multivariate Cox proportional- hazards regression. Of the 537 subjects who were followed for a total of 20,963 person-years, 80.4% (95% confidence interval [95% CI]: 76.4-84.7) survived to 50 years of age with increasing rates of liver-, infectionand malignancy-related deaths observed during recent follow-up. We evaluated non-modifiable risk factors and found worse outcomes associated with male sex (hazard ratio 1.9, 95% CI: 1.1-3.0, P=0.01) and milder genotype (hazard ratio 1.6, 95% CI: 1.1-2.3, P=0.02). The effect of genotype was confirmed in a second model, which included treatment effects. Patients with a milder genotype initiated transfusion significantly later and had reduced blood requirements compared to those with moderate or severe genotypes, although pre-transfusion hemoglobin levels did not differ between genotypes. Our results suggest that early treatment decisions to delay transfusion and different long-term treatment strategies in individuals with milder genotypes have led to adverse longterm effects of under-treated thalassemia and worse survival. We propose that HBB genotype determination and use of this information to aid in decision-making can improve long-term outcomes of thalassemia patients.

Patients with beta thalassemia major (TM) are transfusion-dependent (TD) since early childhood and for life. Development of alloantibodies and autoantibodies against red blood cell (RBC) antigens is increasingly recognized as a significant transfusion hazard, especially among heavily transfused patients. The aim of this study is to assess RBC alloimmunization and autoimmunization rates in TD TM patients treated in our Comprehensive Center of Adult Thalassemia, Hemoglobinopathies and Rare Anemias. TD TM patients, regularly transfused every 2-3 weeks, were included in the study. Clinical and RBC transfusion records, including RBC antibodies, since diagnosis in early childhood, were retrieved from patients' files and from the blood bank database. Forty TD TM patients, > 18 years of age, were included in the study. Alloimmunization was demonstrated in 17 (42.5%) patients. Thirty-four alloantibodies were detected, with the most frequent being RH related (12 of 34, 35.3%) followed by those of the Kell system (8 of 34, 23.5%). Age at first transfusion was positively related to the probability of developing alloantibodies (p = 0.02). Splenectomy was found to be correlated with developing alloantibodies (p = 0.016). Logistic regression analysis of the lifelong probability of developing alloantibodies on the age at first transfusion and splenectomy demonstrates a strong positive relationship (p = 0.002). A substantially high rate of alloimmunization was found among adult TD TM patients. Early initiation of RBC transfusions, avoidance of splenectomy and extended Rh and K antigen matching, can reduce the incidence of alloimmunization in TD TM patients.

BACKGROUND/OBJECTIVES Cardiac T2* magnetic resonance imaging (MRI) is the gold standard to determine myocardial iron overload. As availability of Cardiac T2* is not uniform across developing nations, our strategy was to identify a more accessible and cost effective tool to assess myocardial iron accumulation. As children with transfusion-dependent thalassemia also experience various electrocardiographic abnormalities, we performed electrocardiography (ECG) as well as Cardiac T2* MRI on all children registered in our thalassemia unit. MATERIALS AND METHODS Forty-eight transfusion-dependent thalassemia children with transfusion burden ≥12 times/y (6 to 19 y) in the Thalassemia Unit of the Division of Hematology Oncology, Department of Pediatrics were enrolled. Patients were divided into 3 groups based on severity of T2* value, that is group I (T2* 20). A T2* value >20 was taken as normal. ECG and serum ferritin was also performed on the day of MRI. RESULTS Among the various ECG parameters, QRS duration, and QTc interval were significantly increased if cardiac iron overload was high with a P-value of 0.036 and 0.000, respectively. Also, high serum ferritin predicted a decline in T2* value with a P-value of 0.001. QT interval and QTc interval significantly correlated inversely with T2* (P=0.042, r=-0.295 and P=0.002, r=-0.446, respectively) but not QRS duration (P=0.05, r=-0.282). Serum ferritin also was found to have a significant inverse correlation with T2* value (P=0.000, r=-0.497). CONCLUSIONS Abnormalities on ECG, that is prolongation of QRS duration, QT interval, and QTc interval were significantly associated with cardiac iron overload, that is decrease in the value of Cardiac T2* in our study.

BACKGROUND: Cardiac complications are still the primary cause of mortality and a major cause of morbidity in thalassemia patients. OBJECTIVES: The aims of this study were to assess the prevalence of cardiac involvement in TDT and NTDT beta thalassemia patients and compare between the different forms and severity in both groups. MATERIALS AND METHODS: In this prospective study, 70 TDT and 50 NTDT β-thalassemia patients were recruited; their cardiac status was evaluated by transthoracic echocardiography as per the standard recommendations. Patients' cardiac status was evaluated against the causal risk factors. RESULTS: The mean serum ferritin level was significantly (P < 0.001) higher in the TDT patients (4940 ± 3643 ng/mL) compared to the NTDT patients (634 ± 520 ng/mL). The mean hemoglobin was significantly (P = 0.004) higher in the TDT group (9.2 ± 0.8 vs. 8.7 ± 1.0 g/dL). The prevalence of dilated cardiomyopathy and left cardiac dysfunction in TDT was 18.6%, whereas pulmonary hypertension (PHT) was found in 30% of NTDT patients. CONCLUSION: Dilated cardiomyopathy was prevailing in the adult TDT patients, whereas PHT was the main cardiac complication in NTDT patients.

Background Hypertriglyceridemia thalassemia syndrome (HTS) is not a well understood entity, and is mainly identified in the Indian subcontinent. We present a unique case of this syndrome along with severe autoimmune haemolysis that presented with life-threatening anaemia. Observations An infant with transfusion dependent thalassemia (TDT) presented with suspected mismatched blood transfusion leading to severe haemolysis. Severe haemolysis, lipemic serum were initial findings. Detailed evaluation revealed IgG, C3d positive mixed autoimmune haemolytic anaemia (AIHA), severe hypertriglyceridemia that improved with steroids and least mismatched packed red cell transfusion. Conclusion Children with thalassemia presenting with excessive hemolysis may have mismatched transfusion reaction, alloimmunization or an autoimmune hemolysis. Baseline extended blood grouping, detailed immune hemolytic work-up aids in prompt diagnosis. HTS on a background of autoimmune hemolysis is rare and needs urgent medical support.

Aims To explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low–middle-income country (LMIC) and using the result to guide chelation in transfusion-dependent patients. Methods and results A prospective UK–India collaborative cohort study was conducted in two cities in India. Two visits 13 months apart included clinical assessment and chelation therapy recommendations based on rapid CMR results. Participants were recruited by the local patient advocate charity, who organized the patient medical camps. The average scanning time was 11.3 ± 2.5 min at the baseline and 9.8 ± 2.4 min (P Conclusion For thalassaemia patients in an LMIC, a simplified CMR protocol linked to therapeutic recommendation via the patient camp model led to enhanced chelation therapy and a reduction in cardiac iron in 1 year.

Shaikha Alshamsi,1 Samer Hamidi,2 Hacer Ozgen Narci3 1School of Health and Environmental Studies, Hamdan Bin Mohammed Smart University, Dubai, United Arab Emirates; 2School of Health and Environment Studies, Hamdan Bin Mohammed Smart University, Dubai, United Arab Emirates; 3Department of Health Management, Istinye University, Istanbul, TurkeyCorrespondence: Shaikha AlshamsiHamdan Bin Mohammed Smart University, Academic City, Dubai, United Arab EmiratesEmail Shaikha_Alshamsi@hmbsu.ac.aeObjective: The aim of this study was to assess the indirect burden of patients with transfusion-dependent thalassemia (TDT) in Dubai, the United Arab Emirates (UAE).Methods: Adult patients with TDT were enrolled during blood transfusion sessions. Productivity loss for patients in the preceding four weeks was reported using the validated iMTA Productivity Cost Questionnaire (iPCQ).Results: A total of 161 adult patients with TDT were included in the study. The annual total productivity loss cost at paid work among 79 employed patients was AED 17,230 (USD 4691) (95% CI: 12,302– 22,159), out of which absenteeism contributed AED 10,328 (USD 2812) and presenteeism contributed AED 6902 (USD 1879), whereas the annual total productivity loss cost at unpaid work was AED 4053 (USD 1104) (95% CI: 3471– 4661). The annual mean total indirect cost for paid and unpaid work was AED 21,283 (USD 5795). Monthly income, nationality, and having two and more disease complications were the significant predictors of higher productivity loss costs. Having previously had a splenectomy was a negative and significant predictor of productivity loss costs.Conclusion: TDT was associated with substantial productivity loss and indirect costs in the UAE. Health policies that aim to control transfusion-dependent thalassemia effectively are necessary and could result in cost savings for patients and employers.Keywords: productivity loss, friction cost approach, transfusion-dependent thalassemia, Dubai, United Arab Emirates

Background: Paediatric patients with transfusion dependent thalassemia require regular lifelong red cell transfusions. Blood transfusions increase the risk of iron overload, which can lead to cardiac hemosiderosis. Serum ferritin can be a parameter for evaluating systemic hemosiderosis. Objective: To evaluate the correlation between serum ferritin levels and impaired heart function in children with transfusion dependent thalassemia Methods: A cross sectional study was conducted with transfusion-dependent thalassemia who attended a cardiology and hemato-oncology outpatient clinic from January to December 2018 and had undergone more than 10 transfusion periods. Serum ferritin levels were taken from the mean of 3 measurements before echocardiography. Echocardiography examination was performed by a cardiologist using a 3D Doppler tool to evaluate ejection fraction (EF), tricuspid annular plane systolic excursion (TAPSE) and E / A ratio by calculating the initial diastole (E wave) and atrial contraction (wave A). Data analysis used the Spearman correlation with p Results: There were 45 children with a median age of 10 (2-17) years and had received a median of 18 (10-51) blood transfusions. The mean serum ferritin level was 4,321 (1,168-15,233) ng / mL. Blood transfusion frequency was associated with an increase in serum ferritin (rho 0.74, P Conclusion: Paediatric patients with TDT have decreased cardiac systolic and diastolic function, and serum ferritin correlates with the decreased cardiac function.

Background: Transfusion dependent thalassemia (TDT) patients will progressively experience iron overload due to repeated blood transfusions. It also causes vitamin D hydroxycholecalcoferol (25OH) depletion in the liver parenchyma. Methods: This was a cross-sectional study of children with TDT in Hemato-oncology outpatient clinic, Dr. Soetomo Hospital Surabaya which has enrolled in the study from January-june 2020. Serum ferritin level by Enzym linked Fluorescent Assay (ELFA) and vitamin D hydroxycholecalciferol (25OH) level was examined by the ADVIA centaur VitD assay method. To determine the correlation between serum ferritin level and vitamin D hydroxycholecalciferol (25OH) Spearman correlation was used, significant if p 1000 ng / ml, 12/30 subjects were considered deficient in vitamin D hydroxycholecalciferol (25OH), with vitamin D hydroxycholecalciferol (25OH) level

Background Transfusion is a lifesaving treatment for lots of patients. However, in chronic blood recipients such as thalassemia patients, there are high concerns about alloantibody production that affects the quality of their life. Therefore, research on risk factors of alloimmunization has been started and followed. This study aimed at the determination of correlation probability between some HLADRB1 alleles and alloimmunization in Iranian thalassemia patients. Materials and methods The present study was conducted on 60 alloimmunized and 60 non-alloimmunized transfusion-dependent thalassemia patients. Antibody screening and identification tests were carried out using the tube method, and HLA-DRB1 genotyping was done using a single specific primer-polymerase chain reaction (PCRSSP). Results The results of antibody screening showed that the most prevalent alloantibodies were Anti-K (46.7 %), and followed by Anti-E (32.5 %), Anti-C (15.8 %), Anti-D (13.3 %), Anti-e (8 %), and Anti-c (5.8 %), respectively. DRB1*07:01 was detected more in non-responder patients (28.3 %). However, data analysis showed that there is no significant relationship between DRB1*07:01, *10, *13:01 frequency among responder and non-responder groups (p = 0·195, 0.648, 0.402, respectively). There was not any significant correlation between HLA-DRB1*10 and *13:01 allele and alloimmunization. There was a significant association between HLA-DRB1*12 and alloimmunization (p Conclusion The findings of this study represented that there is a significant relationship between HLADRB1*12 and Kell and E alloantibodies. Although more developed studies on other HLA alleles are demanded, these findings can be valuable in determining important alloimmunization risk factors to better management of transfusion complications.

Thalassemia is the most common hematological transfusion-dependent disease in Thailand. Even though prenatal diagnosis (PND) can detect the condition, many new cases are diagnosed in pediatric practice. This study assessed the clinical outcome of patients with thalassemia who did PND. One hundred and six participants (53 female, 50%), with a median age of 8.5 years (Interquartile range [IQR] 8.00), were enrolled in the study. Twenty-one participants (19.8%) were prenatally diagnosed with thalassemia, with a median age of 8 years (IQR 9.00), 16 were diagnosed with transfusion-dependence thalassemia (TDT), and 5 participants were diagnosed with non-TDT. Another 80.2% did not prenatally diagnose, with a median age of 9 years (IQR 8.00). The PND group found early diagnosis compared with a non-PND group, at a median age of 6 months versus 15 months. There was a significant early diagnosis ( P

Background. Thalassemia is one of the most common genetic hematologic disorders in the world. Despite outstanding achievements in prenatal diagnosis and a decrease in the number of patients, thalassemia is still a significant issue in most parts of the world, especially in the Mediterranean countries. Understanding the factors associated with this condition is crucial to help clinicians and policymakers provides social and medical support for patients to facilitate their lives. This study aims to appraise the quality of life (QoL) and its related paraclinical factors in Iranian transfusion-dependent thalassemia patients. Methods and Materials. This study is a cross-sectional study performed in the thalassemia clinic of Imam-Ali Hospital, Karaj, Iran. The demographic, clinical, and laboratory data of 100 patients with transfusion-dependent thalassemia were recorded. The patients’ QoL was measured by the World Health Organization Quality of Life Instruments Brief (WHOQOL-BREF) version questionnaire. The results were analyzed using SPSS software. Results. This study demonstrated that all four features of life are influenced in transfusion-dependent thalassemia patients. Also, higher educational status and lower serum ferritin levels were associated with better scores in assessing the QoL. On the other hand, an elevated level of AST (aspartate transaminase), ALT (alanine transaminase), and FBS (fasting blood sugar) are associated with lower scores. Conclusion. All features of QoL are correlated to the patients’ laboratory findings. Our data suggest that managing patients’ laboratory indices is attributed to their higher QoL. We also suggest regular screening of patients’ QoL to manage disease complications more efficiently.

In this cross-sectional study we assessed the vascular alterations in retinal and choriocapillaris perfusion in patients affected by β-thalassemia, by means of optical coherence tomography angiography (OCTA). A total of 124 eyes of 62 patients (mean age 44.74 ± 5.79 years old) affected by β-thalassemia (transfusion dependent thalassemia (TDT), non-transfusion dependent thalassemia (NTDT) and minor) were compared to 40 eyes of twenty healthy subjects. We evaluated the vessel density (VD) in superficial capillary plexus, deep capillary plexus, radial peripapillary capillary, choriocapillaris and the foveal avascular zone area. The TDT group showed a statistically significant reduction in retinal and choriocapillaris VD respect to controls and the other groups (p &lt, 0.05). No statistically significant difference was found in OCTA parameters between β-thalassemia minor and controls. The NTDT group showed a significant reduction in VD in deep capillary plexus respect to controls and β-thalassemia minor. Significant negative correlations were shown in TDT group between foveal avascular zone and hemoglobin (r = −0.437, p = 0.044) and between ferritin levels and VD of choriocapillaris (r = −0.431, p = 0.038). The OCTA parameters provided a deeper understanding on retinal and choriocapillaris vascular impairment affected by tissue hypoxia levels and the oxidative stress in different clinical phenotypes of the β-thalassemia.

This study was organized to determine the efficacy and safety of deferasirox (DFX) in reducing the SF of patients with transfusion-dependent thalassemia (TDT). This is a retrospective, descriptive study of 101 transfusion- dependent patients with thalassemia major who were followed for 48 months. Twenty-nine patients who used an alternative chelator either alone or combined, who were not compliant to the treatment, changed the drug due to adverse reactions, and had multiple transfusions and did not complete 4 years of DFX use were excluded. A total 72 out of 101 patients completed the study. SF decreases were noted for the 6-12 and18-year age groups, from a median of 1532 ng/mL to 1190 ng/mL, and from 1386 ng/mL to 1165 ng/mL, respectively (p 0.05). The proportion of patients with SF concentrations2000 ng/mL is decreased (29% at baseline decreased to 15% at the end of the study) during the 48 months. The median SF of those who used30 mg/kg/day (n = 38) increased from 767 ng/mL to 1006 ng/mL, whereas the30 mg/kg/day (n = 34) group's SF concentrations decreased from a median of 1575 ng/mL to 1209 ng/mL (p = 0.029). The decrease of median SF values for Syrian patients was statistically significant (p = 0.043). Most common adverse events were gastric irritation symptoms (19.4%). The total DFX discontinuation ratio was calculated as 9.7%. Although dosages between 25-30 mg/kg/day are adequate to stabilize SF concentrations higher dosages are needed to achieve a statistically significant decrease.

OBJECTIVES: With the advent of COVID-19 in Pakistan, the already fragmented blood transfusion services (BTS) received a severe blow, putting the lives of transfusion-dependent thalassemia children on stake. This study aimed to assess the impact of the COVID-19 on blood transfusion therapy (BTT) of thalassemia patients and suggest ways to ensure safe and reliable blood supplies amid such health crises. MATERIAL AND METHODS: A retrospective, cross-sectional study was conducted from October 2019 (before COVID-19) to July 2020 (during COVID-19) based on the data provided by a thalassemia center, named Help International Welfare Trust, Karachi, Pakistan. SPSS version 24.0 was used for the data analysis. Data were described in the form of means and percentages. RESULTS: There was a significant reduction in the consumption of PRBCs bags after the emergence of COVID-19 (P=0.002). Moreover, the number of thalassemia patients receiving BTT was dropped by 10.56% during the pandemic. There was a strong negative correlation observed between the rising cases of COVID-19 in Pakistan and the number of patients missing their therapy sessions (r=-0.914, P=0.030). A considerable decline in the reserves of all Rhesus-negative blood groups amid the COVID-19 outbreak was also observed. CONCLUSION: The COVID-19 pandemic adversely affected the already suboptimal care catered to thalassemia patients in Karachi, Pakistan. The fear of the virus contraction coupled with the lockdown and restricted mobility has disrupted the entire transfusion chain from donor to the recipient. Collaborated efforts by the government and healthcare authorities are essential to ensure sufficient blood for thalassemia patients amid the pandemic.

Objective: To evaluate the prevalence and severity of malocclusion in children suffering from β-thalassemia and to assess orthodontic treatment need using Grainger’s Treatment Priority Index (TPI) and index of orthodontic treatment need (IOTN)-dental health component (DHC). Methods: A cross-sectional study was conducted on 200 transfusion-dependent children diagnosed with homozygous β-thalassemia and 200 healthy school children aged 11-17 years. The TPI and IOTN-DHC data was recorded for both groups. Total TPI score for each subject was calculated and graded according to malocclusion severity estimate (MSE). Independent sample t-test was used to compare mean TPI scores, overjet and overbite between thalassemic and healthy children. Chi-square test was used to compare the frequency of IOTN-DHC grades, Angle’s classification, and MSE grades between thalassemic and healthy children. Results: The most prevalent malocclusion was Class I in normal children (67.5%) and Class II in thalassemic children (59%). The mean overjet and overbite were significantly (p

Background: Survival in transfusion dependent thalassemia is closely linked to iron overload with severe cardiac iron causing heart failure. MRI guided chelation improves survival in high income countries. We explored the use of rapid MRI to guide therapy in a Lower Middle Income Country (LMIC), India, via locally organized thalassemia patient medical camps. Methods: Rapid cardiac MRI (rCMR) was implemented at two sites with clinical assessment and therapy recommendations based on rCMR findings. Investigations and clinical reassessment were repeated at 13 months. Findings: The baseline visit was attended by 103 patients, the second by 86. Average time of scanning was 10 minutes. At baseline 29% had a cardiac T2* = 17ms). At 13 months more patients were taking 2 oral chelators (21% to 37%, p

Numerous problematic disorders such as vitamin D (Vit-D) deficiency subsequent to large iron loading can be developed in patients with β-thalassemia. The study aimed to estimate Vit-D insufficiency and its risk factors in patients with β-thalassemia. In this multicenter and observational study, all β-thalassemia patients, who referred to 14 hospital-based thalassemia divisions or clinics in Mazandaran province, Iran were included in the study. The data belong to December 2015 until December 2019. The study population was made of transfusion dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT) patients. Serum levels of 25-OHD3 have been measured by high performance liquid chromatography (HPLC) method as ng/mL. Demographic and clinical information along with some biological tests, as well as the results of T2*-weighted magnetic resonance imaging were analyzed. Of 1959 registered patients, 487 (24.9%) patients had Vit-D-related data. The prevalence of Vit-D insufficiency (P = 0.03, sensitivity 67%, specificity 49%, positive predictive value [PPV] 47% and negative predictive value [NPV] 68%). In spite of the national programs for treating Vit-D deficiency and our previous efforts for giving supplements to all patients, Vit-D insufficiency/deficiency is still common in our patients. Also, moderate to severe liver siderosis and raised AST were the independent risk factors for the Vit-D insufficiency.

Background Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. Methods This research aimed to study the leukocyte telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ≥18 years. Leukocyte telomere length was measured by real-time quantitative PCR. Results Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18–57) years, and mean pre-transfusion hemoglobin level was 7.1 (± 1.07) g/dL. The mean telomere to single copy gene (T/S) ratios of patients with TDT and the controls were 0.72 ± 0.18 and 0.99 ± 0.25, respectively (p p = 0.0002), and hemoglobin level (p = 0.044). There was no correlation between telomere length and other factors. Conclusions Our study showed that TDT patients had shorter leukocyte telomere length compared with controls. Leukocyte telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level.

Background The treatment of children with transfusion-dependent thalassemia (TDT) in Malaysia has progressed since 2005. This study provides an updated health-related quality of life (HRQoL) assessment for children with the disorder and the factors affecting the HRQoL. MethodsA cross-sectional HRQoL survey of Malaysian children with TDT was conducted using the PedsQL™ 4.0 Generic Core Scales. Patients with non-transfusion dependent thalassemia and other haemoglobinopathies were excluded. Parent-proxy and self-reported HRQoL scores were obtained using a multi-stage convenient sampling. The relationship between HRQoL scores and demographic factors were tested using association, correlation and regression analysis. Results A total of 368 patients were recruited. The mean (SD) Total Summary Score (TSS) was 80.12(13.87). Predictors for a lower TSS was an increasing age group and the use of dual chelating agents (R2 = 0.057, F (4, 359) = 5.40, p = 2 = 0.075, F (5,358) = 5.80, p = 2 = 0.041, F (1, 362) = 15.60, p =  ConclusionThe HRQoL of TDT children in Malaysia has improved over the last decade owing to the better access in treatment. However, further effort is needed to improve the school functioning dimension.

Early mixed chimerism (MC) can lead to secondary graft rejection post allogeneic hematopoietic stem cell transplantation in transfusion dependent thalassemia (TDT) patients. Reduction of immunosuppression and donor lymphocyte infusions is the mainstay for treating MC. We report our experience of administering unmanipulated stem cell boost (SCB) in reversing progressive early MC. There were 70 transplants done for 69 TDT patients at our center between September 2005 and January 2020. Mixed chimerism was defined by > 5% recipient cells and the severity was assigned according to the proportion of recipient cells as level 1 = 25%. For patients developing MC level 2 and 3, we administered unmanipulated SCB and analyzed its safety and efficacy. Out of 70 transplants 7 (10%) had MC level 2 (3/7) and 3 (4/7). These patients received unmanipulated SCB at a median CD34 cell dose of 4.5 × 10(6)/kg (range—3.5 × 10(6)/kg–5.5 × 10(6)/kg). Overall Response (stable MC and/or transfusion independency) to unmanipulated SCB was seen in 5 patients (71.4%). Five patients (71.4%) developed acute graft versus host disease (GVHD) of which 1 patient expired due to severe GVHD. SCB infusion was well tolerated by majority of our patients. The 3 year overall survival and thalassemia free survival was 85.7% (6/7) and 57.1% (4/7) respectively. Timely monitoring of chimerism is important for detecting early MC. Development of acute GVHD is common after administration of unmanipulated SCB and requires vigilance and prompt management. Unmanipulated SCB is a feasible modality for treating progressive MC and salvaging the graft especially in resource-constrained settings.

Regular blood transfusions in transfusion-dependent thalassemia (TDT) patients can lead to iron overload, causing oxidative stress and sympathovagal imbalance, resulting in increased cardiac complications. We hypothesized that administrating of N-acetylcysteine (NAC) prevents serious adverse events including cardiac complications in TDT patients by reducing systemic oxidative stress and balancing cardiac sympathovagal control. This study was double-blind, randomized control trial, investigating in 59 Thai TDT patients. After randomization, the participants were divided into two groups. The control group received standard care of TDT patient plus placebo, whereas the intervention group received 600 mg of NAC orally for six months. Serum 8-isoprostane, TNF-alpha, IL-10, 24-hour ECG monitoring, echocardiograms and the incidence of thalassemia-related complications were collected. At baseline, no significant difference in any parameters between the control and the intervention groups. At the end of intervention, the incidence of serious adverse events (i.e. infection, worsening thalassemia) was significantly higher in the control group when compared with the intervention group (24.1% vs. 3.3%, p=0.019) (Chi-square test; absolute risk reduction=20.8%, number needed to treat=4.8). The control group also had significantly lower time-dependent HRV parameters, compared with the intervention group (p=0.025 and 0.030, independent t-test). Treatment with NAC restored HRV and reduced serious adverse event in TDT patients, however, no difference in cardiac complications could be demonstrated. NAC could prevent serious adverse events in TDT patients. The proposed mechanism might be the balancing of sympathovagal control.

Thalassemia is one of the most prevalent monogenic diseases most frequently caused by quantitative defects in the production of β-globin leading to severe anemia. Technological advances in genome sequencing, stem cell selection, viral vector development, transduction and gene-editing strategies now allow for efficient ex-vivo genetic manipulation of human stem cells that can lead to correction leading to a meaningful clinical benefit in thalassemia patients. In this review, the status of the gene-therapy approaches available for transfusion dependent thalassemia are discussed, along with the critical criteria that affect efficacy and lessons that have been learned from the early phase trials. Salient steps necessary for the clinical development, manufacturing, and regulatory approvals of gene therapies for thalassemia are also highlighted, so that the potential of these therapies can be realized. It is highly anticipated that gene therapies will soon become a treatment option for patients lacking compatible donors for hematopoietic stem cell transplant and will offer an alternative for definitive treatment of β- thalassemia. This article is protected by copyright. All rights reserved.

Objectives To evaluate any association between pre-transfusion hemoglobin (Hb) levels and thalassemia complications and to identify the Hb cutoff values to predict thalassemia complications. Methods We performed a cross-sectional study in thalassemia patients who attended the Adult Hematology Clinic of the tertiary care University Hospital from October 2017 to October 2018. A point-biserial correlation was used to identify any association between Hb levels and thalassemia complications. A receiver operating characteristic (ROC) curve was used to identify the diagnostic ability of Hb levels to predict thalassemia complications and identify Hb cutoff values. Results Out of the 102 patients, there were 53 transfusion dependent thalassemia (TDT) patients and 49 non-transfusion dependent thalassemia (NTDT) patients. In theTDT group, Hb levels showed a negative correlation with severe hepatic iron overload and hypogonadism. The cutoff Hb levels to predict severe hepatic iron overload and hypogonadism were ≤7.01 and 6.81 g/dL, respectively, at which points the area under the ROC curve (AUC) were 0.721 and 0.708, respectively. In the NTDTgroup, Hb levels were negatively correlated with hepatic iron overload, osteoporosis, and pulmonary hypertension. The cutoff values of Hb levels to predict hepatic iron overload, osteoporosis, and pulmonary hypertension were ≤8.24, 7.16, and 7.16 g/dL, respectively, at which points the AUC were 0.923, 0.715, and 0.725, respectively. Conclusions Lower Hb level was associated with more frequent complications in both TDT and NTDT patients. The Hb cutoff levels to predict these complications were identified.

Heart disease remains a leading cause of morbidity and mortality in transfusion-dependent thalassemia (TDT), which can be attributed to several factors but primarily develops in the setting of iron overload. This was a retrospective cohort study utilizing Webthal® patient data from five major centers across Italy. Patients without heart disease were followed-up for 10 years (2000-2010) and data were collected for demographics, splenectomy status, serum ferritin and hemoglobin levels, and comorbidities associated with heart disease. Among 379 patients analyzed (mean age 22.9 ± 5.1years, 47.8% men), 44 (cumulative incidence: 11.6%) developed heart disease during the period of observation. Splenectomy (p = 0.002) and serum ferritin level (p

Thalassemia is among the most common genetic diseases. Patients with severe forms of the disease are transfusion-dependent, leading to iron overload. A condition which can eventually develop in the iron-loaded heart is iron overload cardiomyopathy, a debilitating disease that accounts for the majority of deaths in thalassemia patients. Areas covered: This review article provides a comprehensive summary of the diagnosis and treatment of cardiac iron overload in transfusion-dependent thalassemia patients, with discussion covering current weak points and potential improvements of the relevant diagnostic and therapeutic strategies. Expert commentary: Current limitations of various diagnostic techniques for iron overload cardiomyopathy include suboptimal accuracy, untimely detection, or inadequate accessibility, and novel modalities are required to overcome these shortcomings. Treatment should address key pathophysiologic mechanisms of iron overload cardiomyopathy, which include cardiac iron mishandling and iron-induced oxidative injury. Apart from the promotion of iron removal by chelators, prevention of cardiac iron deposition and attenuation of oxidative damage should also be rigorously investigated on a cell-to-bedside basis.

Introduction of MRI techniques for identifying and monitoring tissue iron overload and the current understanding of iron homeostasis in transfusion-dependent (TDT) and non-transfusion-dependent thalassemia have allowed for a more robust administration of iron chelation therapies. The development of safe and efficient oral iron chelators and the insights gained from large-scale prospective studies using these agents have improved iron overload management. A significant reduction in iron toxicity-induced morbidity and mortality and improvements in quality of life were observed in TDT. The appropriate management of tissue-specific iron loading in TDT has been portrayed using evidence-based data obtained from investigational studies.

The aim of our study was to evaluate the Greek version of the transfusion-dependent quality of life (TranQol) questionnaire and report our experience of using this novel disease-specific quality of life (QoL) measure in patients with transfusion-dependent thalassemia (TDT). The TranQol and SF-36v2 questionnaires were administered to 94 adult TDT patients with a mean age of 32.1 years (SD = 7, range = 19–58), recruited from the Adult Thalassemia Unit of Hippokration General Hospital of Thessaloniki, Greece. The TranQol was evaluated in terms of construct validity, reliability, and responsiveness. There was a moderately strong correlation between the TranQol summary and both the SF-36v2 physical and mental component summaries (r = 0.4, p

With regular blood transfusions and modern medical management strategies, transfusion-dependent thalassemia (TDT) patients are currently living into adulthood, but they still suffer from the chronicity of the disease and its complications. This study was aimed to assess the health-related quality of life (HRQoL) scores in pediatric TDT patients compared with healthy controls.The PedsQL 4.0 Generic Core Scales were administered to 80 pediatric TDT patients (aged 5 to 18 y, child self-report) and their parents (parent-proxy report), as well as age-matched and sex-matched healthy controls (80 participants and their parents).Patients with TDT and their parents rated lower HRQoL scores in all domains (physical, emotional, social, and school functioning) compared with the healthy population (P0.01). The univariate analysis indicated that the total HRQoL score for children's self-reports was negatively predicted by high ferritin levels and the presence of any complication. The only negative predictor of the total HRQoL score in multivariate analyses was a high ferritin level (1800 ng/dL).This study showed that thalassemia has a negative impact on HRQoL when compared with a healthy population. For a better quality of life, intensive treatment should be applied for complications and high ferritin levels.

Thalassemias are emerging as a global public health concern. Due to remarkable success in the reduction of childhood mortality by controlling infectious diseases in developing countries, thalassemias are likely to be a major public health concern in the coming decades in South Asia. Despite the fact that Bangladesh lies in the world’s thalassemia belt, the information on different aspects (epidemiology, clinical course, mortality, complications and treatment outcomes) of thalassemias is lacking. In this comprehensive review, the aim is to to depict the epidemiological aspects of thalassemias, mutation profile and current treatment and management practices in the country by sharing the experience of dealing with 1178 cases over 2009–2014 time periods in a specialized thalassemia treatment centre. We have also discussed the preventative strategies of thalassemias from the context of Bangladesh which could be effective for other developing countries.

This was a prospective observational study to evaluate abnormalities in lipid profile in 50 children with transfusion dependent thalassemia. Dyslipidemia characterized by high triglycerides, low high density lipoprotein (HDL), and high total cholesterol: HDL ratio was noted. These pro atherogenic risk factors may be lead to significant cardiovascular morbidity in these patients.

Deferasirox is a once-daily oral iron-chelation agent approved by the US Food and Drug Administration in November 2005. The authors aimed to evaluate efficacy, safety, and satisfaction of patients regarding twice-daily dose of deferasirox in patients with thalassemia who are resistant to once-daily regimen.In this historical cohort multicenter study, 34 patients with beta-thalassemia major resistant or intolerant to once-daily dose of deferasirox (35 mg/kg/d) were investigated in 2016. Patients were registered at 3 thalassemia referral centers in Shiraz, southern Iran and Tehran, the capital of Iran. All patients were followed for 1 year and monitored by regular physical examination, laboratory data, serum ferritin levels, and heart and liver T2 magnetic resonance imaging.Mean age of thalassemia patients was 25.6±8.1 (8 to 40) years, including 22 female individuals and 12 male individuals. Serum ferritin levels significantly decreased during the study period (2021±955 at baseline vs. 1228±894 at the end of the study, P0.001). Liver T2 magnetic resonance imaging of the patients demonstrated a significant improvement during the study. 73.3% of patients showed normal values at the end of study compared with 28.1% at the baseline (P0.001). Drug side effects were reported only in 2 patients (5.8%) including 1 patient with abdominal pain and 1 with leukopenia and thrombocytopenia.It seems that deferasirox can be used with increased dose and twice daily with acceptable efficacy in unresponsive or intolerant thalassemia patients to once-daily dose. Close monitoring of the patients is necessary to detect and manage any possible adverse events.

Background and Objectives Recently, researchers have shown an increased interest in thalassemia for detecting susceptible factors in alloimmunization development. Alloimmunization, especially against Rh and Kell blood, occurs in 30% of thalassemia dependent transfusion (TDT) patients. The aim of this study is to determine the role of HLA-DRB1*11 and HLA-DRB1*13 group-specific alleles in the production of Rh and Kell alloantibodies. Materials and Methods 106 TDT patients were recruited for this study (54 responders and 52 non-responders). Responder patients developed Rh, Kell and/or specificities alloantibodies. HLA genotyping was done with Sequence-Specific Primers (SSP-PCR) and the results were compared between two groups. Results A significant association was found between anti-K (P=0.021, OR=2.546, 95%CI) and anti-E (P=0.049, OR=2.304, 95%CI) alloantibodies production with DRB1*11, respectively. Development of Anti-K and Anti-E alloantibodies were associated with DRB1*11 (P = 0.021, OR = 2.546, 95%CI) (P = 0.049, OR = 2.304, 95%CI), respectively. Further analysis showed that DRB1*11 is more frequent in multi responders (responder with both Rh and Kell alloantibodies) than mono-responders, 71% Versus 29%. There was not found any association between the DRB1*13 group-specific allele and the production of alloantibodies (P = 0.584, OR = 0.308, 95%CI). Conclusions The evidence from this study suggests that detecting the DRB1*11 group-specific allele before starting transfusion can be useful to identify susceptible patients, increase HSCT transplantation compatibility and blood transfusion management.

This study aimed to determine the predictors of Quality of Life (QoL) in Transfusion-Dependent Thalassemia (TDT) patients based on PRECEDE (Predisposing, Reinforcing and Enabling Constructs in Educational Diagnosis and Evaluation) model. This cross-sectional analytical study was performed on 389 TDT patients who were under treatment in four thalassemia centers in Tehran, Iran. Data gathering instrument consisted of three parts: socioeconomic and demographic information, the Persian version of the six standardized questionnaires for measuring some of the potential predictive factors of QoL in TDT patients based on the PRECEDE model constructs, and a researcher-made questionnaire to assess knowledge of patients about health- and QoL-promoting behaviors and enabling factors involved in health- and QoL-promoting behaviors. Using AMOS 23.0, the structural equation modeling with maximum likelihood estimation was conducted to test the proposed hypotheses. Associations of QoL with all of the PRECEDE model constructs, including anxiety–depression, self-efficacy, perceived barriers, knowledge, enabling factors, and reinforcing factors were significant (all p < 0.001). Anxiety–depression and perceived barriers were the significant negative predictors of QoL in TDT patients, whereas health-promoting lifestyle was the significant positive predictor of QoL in TDT patients. The final conceptual model of the study was adequately fit and can be applied as a framework for future educational-supportive programs aimed at improving the QoL in TDT patients.