Prevalence of hypogonadism in transfusion-dependent ß-thalassemia patients of Bangladesh: investigating the role of serum ferritin level as a diagnostic tool

ABSTRACT Introduction: Hypogonadism is one of the most frequent complications in transfusion-dependent thalassemia patients and early recognition and treatment is the core element in restoring impaired gonadal function. Despite the high burden of disease, relevant studies are scarcely addressing the gonadal function of such patients in Bangladesh. The pattern of gonadal function in transfusion-dependent thalassemia patients must be characterized before planning a generalized management plan. Moreover, since iron overload is a key reason behind hypogonadism in thalassemia patients, investigating the role of serum ferritin level as a diagnostic tool for hypongadism was also an aim of this study. Methods: This cross-sectional study was conducted at the Department of Transfusion Medicine of the Bangabandhu Sheikh Mujib Medical University. According to the inclusion and exclusion criteria, a total of 94 patients were enrolled in this study. A detailed history and thorough clinical examination were carried out in each patient and recorded using a pretested structured questionnaire. In addition, the laboratory assessment of serum ferritin, luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol in serum were also performed. The data were analyzed using the STATA (v.16). Results: The mean age of the patients with transfusion-dependent thalassemia was 18.81 ± 4.65 (SD), with 53.3% of the patients being male. The overall prevalence of hypogonadism was 35.11%, 18.1% being normogonadotropic, 11.7% being hypogonadotropic and 5.3% being hypergonadotropic. The serum ferritin level was significantly higher (p < 0.001) in patients with hypogonadism (Eugonadal: 2,174.79 (± 749.12) ng/ml; Hypogonadal: 3,572.59 (± 1,199.49) ng/ml). The area under the receiver operating characteristic (ROC) curve of serum ferritin was high (0.83) and the p-value was highly significant (< 0.001). Conclusion: Therefore, the serum ferritin level and gonadal hormone analysis of transfusion-dependent thalassemia patients can be considered a screening tool for assessing gonadal function and early detection and prevention of hypogonadism.

Aumento da Espessura Médio-intimal Aórtica e sua Relação com Estresse Oxidativo Elevado em Pacientes com Talassemia Menor / Aortic Intima Media Thickness is Increased and Closely Related to Elevated Oxidative Stress Increases in Beta Thalassemia Minor

Resumo Fundamento A espessura médio-intimal (EMI) da artéria aorta abdominal (EMI-A) pode ser um marcador precoce de aterosclerose subclínica e um indicador objetivo de estresse oxidativo em pacientes com talassemia menor. Objetivo Avaliar se as EMIs da artéria aorta e da artéria carótida (EMI-C) se alteram com estresse oxidativo, e examinar a relação entre esses parâmetros em pacientes com talassemia menor. Métodos O estudo incluiu 80 pacientes diagnosticados com talassemia menor, e 50 indivíduos sadios com idade e sexo similares. Após procedimentos de rotina, as amostras de sangue foram coletadas dos grupos de estudo para a medida da homeostase tiol/dissulfeto e da albumina modificada pela isquemia (AMI). As medidas da EMI-C foram realizadas a partir de quatro regiões diferentes (artéria carótida externa direita e esquerda e artéria carótida interna direita e esquerda) por ultrassonografia, e a medida da EMI-A foi realizada por ultrassonografia abdominal. Um valor de p<0,05 foi definido como estatisticamente significativo. Resultados Nos pacientes com talassemia menor, os níveis de tiol nativo e tiol total, e a razão tiol nativo/tiol total foram mais baixos, e os valores de AMI, razão dissulfeto/tiol nativo, e razão dissulfeto/tiol total foram mais altos que no grupo controle. A EMI-A foi significativamente maior no grupo de pacientes com talassemia menor que nos controles (1,46±0,37 vs 1,23±0,22 e p<0,001). Quando os parâmetros associados com EMI-A na análise univariada foram avaliados por regressão linear multivariada, EMI-A apresentou uma relação positiva, e os níveis de tiol nativo e tiol total apresentaram uma forte relação negativa com AMI (p<0,01). Conclusão Nós demonstramos, pela primeira vez, um aumento no estresse oxidativo com a elevação da EMI-A, e valores inalterados da EMI-C em pacientes com talassemia menor.

Abstract Background Abdominal aortic intima media thickness (A-IMT) may be an early marker of subclinical atherosclerosis and an objective indicator of increased oxidative stress in beta-thalassemia minor patients. Objective To evaluate whether aortic and carotid IMTs change with oxidative stress and to assess the relationship between these parameters in beta-thalassemia minor patients. Methods The study included 80 patients diagnosed with beta-thalassemia minor, and 50 healthy individuals with similar age and gender. After routine procedures, blood samples were collected from the study groups for thiol-disulfide hemostasis and ischemia-modified albumin (IMA). C-IMT measurements were performed in four different regions (right and left internal and external carotid artery) by ultrasonography. In addition, A-IMT measurement was performed by abdominal ultrasonography. Statistically significant p value was set as <0.05 for all comparisons. Results In beta-thalassemia minor patients, native thiol, total thiol and native thiol / total thiol ratio were lower, and the IMA, disulfide / native thiol ratio and disulfide / total thiol ratios were higher than in healthy control group. A-IMT measurement was significantly higher in beta-thalassemia minor group than controls (1.46±0.37 vs 1.23±0.22 and p<0.001). When the parameters associated with A-IMT in univariate analysis were evaluated by multivariate linear regression analysis, A-IMT was positively related, and native thiol and total thiol levels were negatively and closely related to IMA (p<0.01). Conclusion We demonstrated, for the first time, that oxidative stress status increased with increased A-IMT, while C-IMT remained unchanged in beta-thalassemia minor patients.

The inverse correlation between serum levels of anti-pneumococcal and ferritin after pneumococcal vaccination in splenectomised beta thalassemia major

Splenectomy is necessary in beta thalassemia major patients when the spleen becomes hyperactive, leading to extreme destruction of erythrocytes. This study assessed the ferritin effect on serum pneumococcal antibody response following pneumococcal vaccination, in patients with beta thalassemia major after splenectomy. In this case series study, convenience sampling was used to recruit 347 splenectomised beta thalassemia patients under the auspices of Jahrom University of Medical Sciences. Demographic data such as age, sex, and time after splenectomy were recorded by a questionnaire. All participants had been splenectomised and received a dose of Pneumovax1 23 vaccine 14 days before surgery. The IgG antibody responses to pneumococcal vaccine and levels of serum specific ferritin were determine by commercial enzyme immunoassay kits. For the analysis, SPSS software version 16 was used. A p-value less than 0.05 was considered statistically significant. Most of the participants (63.4 percent) were hypo-responders to pneumococcal vaccine. Also, serum anti-pneumococcal IgG antibody was related to post splenectomy duration and serum ferritin (p 0.05). An important result was a relation of serum anti-pneumococcal IgG antibody to serum ferritin according to post splenectomy duration groups. Therefore, in three groups of post splenectomy duration, the serum ferritin was higher in hypo-responder than in good responder subjects. Our results indicate that serum anti-pneumococcal IgG antibody decreased with increment of serum ferritin and post splenectomy duration. Thus, there is a need to re-address the approach towards revaccination in this immune-compromised group of patients by administering a booster pneumococcal vaccination in an attempt to recover immunity and reduce morbidity(AU)

La esplenectomía es necesaria en pacientes con beta talasemia mayor cuando el bazo se vuelve hiperactivo, lo que lleva a una destrucción extrema de los eritrocitos. Este estudio evaluó el efecto de la ferritina sobre la respuesta de anticuerpos antineumocócicos en suero después de la vacunación antineumocócica, en pacientes con talasemia beta mayor a los que se les realizó esplenectomía. En este estudio de serie de casos, se utilizó un muestreo de conveniencia para reclutar a 347 pacientes con beta talasemia esplenectomizados bajo los auspicios de la Universidad de Ciencias Médicas de Jahrom. Los datos demográficos como la edad, el sexo y el tiempo después de la esplenectomía se registraron mediante un cuestionario. Todos los participantes fueron esplenectomizados y recibieron una dosis de la vacuna Pneumovax® 23, 14 días antes de la cirugía. Las respuestas de anticuerpos IgG a la vacuna neumocócica y los niveles de ferritina sérica específica se determinaron mediante estuches comerciales de inmunoensayo enzimático. Para el análisis se utilizó el programa SPSS versión 16. Un valor de p inferior a 0,05 se consideró estadísticamente significativo. La mayoría de los participantes (63,4 por ciento) resultaron hiporrespondedores a la vacuna antineumocócica. Además, el anticuerpo sérico antineumocócico IgG se relacionó con la duración de la esplenectomía y la ferritina sérica (p0,05). Un resultado importante fue la relación del anticuerpo sérico IgG antineumocócico con la ferritina sérica según los grupos de duración postesplenectomía. Por lo tanto, en tres grupos de duración posterior a la esplenectomía, la ferritina sérica fue mayor en los sujetos con hiporrespuesta que en los sujetos con buena respuesta. Nuestros resultados indican que el anticuerpo sérico IgG antineumocócico disminuyó con el incremento de la ferritina sérica y la duración posterior a la esplenectomía. Por lo tanto, existe la necesidad de volver a abordar el enfoque hacia la revacunación en este grupo de pacientes inmunocomprometidos mediante la administración de una vacunación antineumocócica de refuerzo en un intento por recuperar la inmunidad y reducir la morbilidad(AU)

General considerations for clinical trials design of gene therapy drug for β-thalassemia / 白血病·淋巴瘤

β-thalassemia is a single-gene genetic disease caused by β globin gene mutations leading to the fact that red blood cells are unable to form normal adult hemoglobin, and then patients develop hemolytic anemia. Current treatment regimens mainly include allogenetic hematologic stem cell transplantation, symptomatic regular blood transfusions and the use of iron removers to reduce iron load. Some severe patients have quite poor prognoses and deadly consequences if not treated timely. Genetically modified autohematopoietic stem cells can provide a new treatment option for patients with β thalassemia, which may achieve a long-term and stable increase in hemoglobin level through a single dose, making one-time cure β-thalassemia possible. This paper reviews the key elements of clinical trial design for β-thalassemia gene therapy from the aspects of efficacy evaluation endpoints, clinical trial design, enrollment population, and subject monitoring in order to provide a reference for pharma-therapeutic research and development enterprises.

Clinical study of unrelated mismatched hematopoietic stem cell transplantation for β-thalassemia major / 中华器官移植杂志

Objective:To explore the efficacy and safety of unrelated mismatched hematopoietic stem cell transplantation(HSCT)for thalassemia major.Methods:For this retrospective cohort study, 15 patients with β-thalassemia major underwent unrelated mismatched HSCT between January 2018 and April 2022. There were 8 males and 7 females with a median age of 7(3-12)years and a median ferritin level of 3 417.3(223-14 485)μg/L. The conditioning regimens on the basis of fludarabine(Flu), busulfan(Bu)and cyclophosphamide(CTX)and GVHD prophylaxis on the basis of cyclosporine(CsA), mycophenolate mofetil(MMF), anti-human thymocyte immunoglobulin(ATG)plus low-dose post-cyclophosphamide(PTCy)and mesenchymal stem cells were offered.Results:Up until April 1, 2022, 15 children were successfully implanted during a median follow-up period of 24.1(11-49)months and all of them achieved stable donor chimerism. The median time to neutrophil and platelet engraftment were 12(11-22)and 14(8-38)days respectively. Except for 2 deaths, 13 cases survived. The estimated 2-year probability of overall survival(OS)and thalassemia-free survival(TFS)were both 86.67%. There were 5 cases of acute graft versus host disease (aGVHD) below grade Ⅱ, 2 cases of grade Ⅲ to Ⅳ aGVHD, and 3 cases of localized chronic graft versus host disease (cGVHD) after transplantation. No gengralized cGVHD occurred. Both cytomegalovirus and Epstein-Barr virus were activated in five recipients.Conclusions:Unrelated mismatched donor HSCT is both safe and feasible for thalassemia major.

Comparative metavirome analysis in polytransfused patients

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 Ribeirão 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.

Effectiveness of Using Mean Corpuscular Volume and Mean Corpuscular Hemoglobin for Beta-thalassemia Carrier Screening in the Guangdong Population of China / 生物医学与环境科学（英文）

Beta (β)-thalassemia is one of the most common hemoglobinopathies worldwide, creating major public health problems and social burdens in many regions. Screening for β-thalassemia carriers is crucial for controlling this condition. To investigate the effectiveness of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) for screening β-thalassemia, retrospective data were analyzed for 6,779 β-thalassemia carriers subjected to genetic testing following thalassemia screening in Guangdong province between January 2018 and December 2019. Prevalent mutations observed included CD41/42 (-TTCT) (38.43%), IVS-II-654 (C > T) (25.71%), -28 (A > G) (15.78%), CD17 (AAG > TAG) (10.03%), and β

Nature and severity of dental malocclusion in children suffering from transfusion-dependent (-thalassemia major

ABSTRACT 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<0.001) greater in thalassemic children than in healthy children. Severe tooth displacements were 3.5 times greater in thalassemic children, compared to controls. A greater proportion of thalassemic children were in IOTN grades 3 and 4, compared to the controls (p<0.001). MSE grades 4 and 5 were significantly (p<0.001) more prevalent in thalassemic children, compared to the controls. Conclusion: There is a high prevalence of Angle's Class II malocclusion in thalassemic children. Majority of these children are categorized in higher grades of IOTN-DHC and TPI-MSE, showing a great severity of malocclusion and high orthodontic treatment needs.

RESUMO Objetivo: Avaliar a prevalência e gravidade da má oclusão em crianças que sofrem de beta-talassemia e mensurar a necessidade de tratamento ortodôntico usando o Índice de Prioridade de Tratamento (IPT) de Grainger e o Índice de Necessidade de Tratamento Ortodôntico (Index of Orthodontic Treatment Need - IOTN) - Componente de Saúde Dental (Dental Health Component - DHC). Métodos: Um estudo transversal foi conduzido com 200 crianças com diagnóstico de beta-talassemia homozigótica dependentes de transfusão e 200 crianças saudáveis em idade escolar, entre 11 e 17 anos. Os dados do IPT e do IOTN-DHC foram documentados para ambos os grupos. A pontuação total do IPT para cada sujeito foi calculada e classificada de acordo com a Estimativa de Severidade da Má oclusão (ESM). O teste t para amostras independentes foi usado para comparar os escores médios de IPT, sobressaliência e sobremordida, entre as crianças saudáveis e as com talassemia. O teste qui-quadrado foi usado para comparar a frequência dos escores do IOTN-DHC, a classificação de Angle e os escores do ESM entre crianças com beta-talassemia e crianças saudáveis. Resultados: A má oclusão mais prevalente foi a Classe I em crianças normais (67,5%) e a Classe II em crianças com beta-talassemia (59%). Os valores médios de sobressaliência e a sobremordida foram significativamente (p< 0,001) maiores em crianças com beta-talassemia do que em crianças saudáveis. Os deslocamentos dentários graves foram 3,5 vezes maiores em crianças com beta-talassemia em comparação com os controles. Uma proporção maior de crianças com beta-talassemia estava nos escores 3 e 4 do IOTN em comparação com os controles (p <0,001). Os escores 4 e 5 de ESM foram significativamente (p< 0,001) mais prevalentes em crianças com beta-talassemia em comparação com os controles. Conclusão: Há uma alta prevalência de má oclusão de Classe II de Angle em crianças com beta-talassemia. A maioria dessas crianças é categorizada em escores superiores de IOTN-DHC e IPT-ESM, mostrando uma grande gravidade de má oclusão e alta necessidade de tratamento ortodôntico.

Discriminant indexes to simplify the differential diagnosis between iron deficiency anemia and thalassemia minor in individuals with microcytic anemia

SUMMARY INTRODUCTION: Microcytic anemias are very common in clinical practice, with iron deficiency anemia (IDA) and thalassemia minor (TT) being the most prevalent. Diagnostic confirmation of these clinical entities requires tests involving iron metabolism profile, hemoglobin electrophoresis, and molecular analysis. In this context, several discriminant indices have been proposed to simplify the differential diagnosis between IDA and TM. OBJECTIVE: The aim of this paper was to demonstrate the clinical relevance of the use of discriminant indices in individuals with microcytic anemia to simplify the differential diagnosis between iron deficiency anemia and minor thalassemia. METHODS: A bibliographic and cross-sectional search was performed in the PubMed, SciELO and LILACS databases, using the following descriptors: iron deficiency anemia, thalassemia minor, and differential diagnosis. RESULTS: More than 40 mathematical indices based on erythrocyte parameters have been proposed in the hematological literature in individuals with microcytosis. Green & King indexes (IGK), Ehsani index, and erythrocyte count (RBC) had excellent performances, especially when their efficacy was observed in adults and children. CONCLUSIONS: Confirmatory tests for differential diagnosis between IDA and TM require time-consuming and costly methods. Despite the excellent performances of IGK, Ehsani index, and RBC, none of them presented sufficient sensitivity and specificity to establish a diagnosis. However, they can provide a powerful additional tool for diagnostic simplification between IDA and TM.

RESUMO INTRODUÇÃO: Anemias microcíticas são muito comuns na prática clínica, sendo a anemia ferropriva (AF) e a talassemia menor (TM) as mais prevalentes. A confirmação diagnóstica dessas entidades clínicas requer testes que envolvem o perfil do metabolismo do ferro, eletroforese de hemoglobinas e análises moleculares. Nesse contexto, vários índices discriminantes têm sido propostos para simplificação do diagnóstico diferencial entre AF e TM. OBJETIVO: O objetivo deste artigo foi demonstrar a relevância clínica da utilização de índices discriminantes em indivíduos com anemia microcítica, para simplificação do diagnóstico diferencial entre anemia ferropriva e talassemia menor. MÉTODOS: Foi realizada uma pesquisa bibliográfica e transversal nas bases de dados PubMed, SciELO e Lilacs, utilizando-se os seguintes descritores: anemia ferropriva, talassemia menor e diagnóstico diferencial. RESULTADOS: Mais de 40 índices matemáticos baseados em parâmetros eritrocitários foram propostos na literatura hematológica em indivíduos com microcitose. Os índices de Green & King (IGK), o índice de Ehsani e a contagem de eritrócitos (RBC) obtiveram excelentes desempenhos, especialmente quando sua eficácia foi observada em adultos e crianças. CONCLUSÕES: Testes confirmatórios para o diagnóstico diferencial entre AF e TM demandam métodos que consomem bastante tempo e alto custo. Apesar dos excelentes desempenhos do IGK, do índice de Ehsani e do RBC, nenhum deles possui sensibilidade e especificidade suficientes para firmar diagnóstico. No entanto, podem fornecer uma poderosa ferramenta adicional para simplificação diagnóstica entre AF e TM.

Sehgal index and its comparison with Mentzer's index and Green and King index in assessment of peripheral blood smear with marked anisopoikilocytosis

Background: Mild microcytic hypochromic anaemias due to iron deficiency (IDA) and beta thalassemia trait(β-TT) continue to be a cause of significant burden to the society, particularly in the poorer developing countries. The objective of the present study was to study the RBC based indices in patients of marked anisopoikilocytosis in determining the etiology of it, to standardize few automated red cell parameters, and also objective grading of RBC morphology on peripheral smear and interpreting its utility in indicating a diagnosis. Also, to establish a relation between value of RBC indices with that of degree of anisocytosis.Methods: A total of 500 patients diagnosed with mild microcytic hypochromic anaemia on complete blood count and peripheral blood film were included in the study. Hb, RBC count, MCV, MCH and RDW obtained from the electronic cell counter were used to calculate discrimination indices by various mathematical formulae. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and Youden’s index (YI) were calculated.Results: Green and King index demonstrated the lowest sensitivity of 70.51%. Mentzer index demonstrated the highest specificity of 96.80%. The highest and lowest PPV were found for Mentzer index (97.09%) and Sehgal index (92.81%) respectively. Sehgal’s index demonstrated the highest NPV of 95.96% and lowest NPV was exhibited by G and K (87.9%). The highest and the lowest values for Youden’s index were shown by Sehgal’s index (87.82%) and G and K index (68.47%).Conclusions: Sehgal’s index followed by Mentzer index are highly sensitive and reasonably specific in differentiating β-TT from IDA and none of the indices is 100% sensitive and specific. Though HbA2 estimation is the gold standard for diagnosing β-TT, in developing countries, Sehgal index followed by Mentzer et al, index can be used to screen mild microcytic hypochromic anaemia cases to eliminate as many false positive cases as possible to reduce the financial cost.

Experience with NESTROFT for screening for thalassemia trait/ minor: evaluation against CBC and HPLC in a high prevalence region in Saurashtra, Gujarat, India

Background: Hemoglobinopathies pose a significant health burden in India. Prevention programmes can significantly reduce this burden. Although sophisticated methods of screening for β thalassemia trait are available, a cheap and simple method is beneficial for population screening. Although the Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) has been evaluated in many studies, sample sizes were small in some and many earlier studies have not done complete blood count (CBC) and High-Performance Liquid Chromatography (HPLC) in all the cases. We evaluate the suitability of NESTROFT for detection of β-thalassemia trait in a high prevalence region in Saurashtra, Gujarat.Methods: Here, 1000 unrelated individuals were studied. NESTROFT, CBC and estimation of HbA2 and HbF or other hemoglobin variants were done by HPLC.Results: Prevalence of β thalassemia trait was 7.8% in this population. NESTROFT showed an overall sensitivity and specificity of 94.87 and 85.38 respectively for the detection of β thalassaemia trait. Using red cell indices (MCH <27 pg and MCV <80 fl), One β thalassemia trait with normal indices would have been missed. Among twelve individuals with other hemoglobinopathies (HbS, HbD, HbE, δβ thalassemia trait or HPFH), seven had a positive NESTROFT while three had normal MCV & MCH values.Conclusions: NESTROFT is a cost-effective sensitive test which does not require any equipment and can be done in remote areas. It remains a useful first line screening test when large populations have to be screened.

Pattern of hemoglobinopathies and thalassemia in Manipur, India

Background: Hemoglobinopathies are the commonest genetic disorders worldwide. Thalassemia Major, Thalassemia Intermedia and Sickle Cell Disease are the major disorders that require lifelong management and are to be considered for prevention. In India, Beta-Thalassemia is prevalent across the country, with an average frequency of carriers being 3-4%.Methods: This is a cross sectional study conducted between June 2016 - May 2017 in the Department of Medicine, RIMS Imphal in 453 patients as a workup for anemia and clinically suspected cases of Hemoglobinopathy or beta thalassemia. Blood samples were collected and sent for Haemoglobin Electrophoresis using cellulose alkaline technique.Results: Among the 453 cases of the population surveyed, 35% showed the presence of abnormal hemoglobin. 16% were found to be beta thalassemia carrier, 11.69% HbE trait, 6.62% Homozygous HbE, 0.4% beta thalassemia and 0.7% had Hereditary persistence of HbF.Conclusions: High prevalence of Beta Thalassemia trait occurred more frequently than other Hemoglobinopathies. The study concludes that it is immensely important epidemiologically to explore the haemoglobin variants in Manipur so that the carriers can be detected for prevention of more serious disorder in the future generations.

P-Wave and QT Dispersion in Children With βeta-Thalassemia

Aim:This study aimed atassessingP-wave and QT interval dispersion in children with β-thalassemia and to correlate them with various laboratory and echocardiographic data. Methodology:Subjects comprised of 30 children with β-thalassemia major as the patient group. 30 healthy children matched for age and sex served as the control group. All patients were evaluated clinically as well as by echocardiography and 12 leads ECG. The type of study isprospective case control study.Results:There was a statistically significant increase ofInterventricular Septal end diastole(IVSd),Interventricular Septal end systole(IVSs),Left Ventricular Internal Diameter end diastole (LVIDd), Left Ventricular Internal Diameter end systole(LVIDs) andLeft Ventricular Posterior Wall end diastole(LVPWd) in patients as compared to controls (Mean ±SD = 0.950±0.166, 0.863±0.103, 3.983±0.456, 2.947±0.535and 0.797±0.165 respectively) (P < 0.05). Moreover, there were a significant increase of LV mass (Mean ±SD = 107.267±26.736, P= 0.002) and LV mass index of the studied patients (Mean ±SD = 106.900±22.651, P = 0.005)compared to the controls. There were significant decrease ofejection fraction(EF%)(Mean ±SD = 60.373 ± 8.088, P = 0.032)and fractional shortening(FS%) (Mean ±SD = 29.495 ± 4.171, P = 0.026) of the studied patients compared to control group. Both P wave dispersion (PWd) (Mean ±SD = 33.667 ± 13.767, P = 0.029) and QT dispersion (QTd) (Mean ±SD = 53.000 ± 18.411, P = 0.001) were significantly higher in patients compared to controls. There was a significant positive correlation between PWd and serum ferritin(r =0.551,P-value=0.002), LVIDd (r =0.406,P-value=0.026), LVPWd(r =0.461,P-value=0.010), LV mass (r =0.412,P-value=0.024), and LV mass index(r = 0.379,P-value=0.039). While, there were a significant positive correlations between QTd and serum ferritin (r =0.654,P-value <0.001), LVIDd (r = 0.388,P-value =0.034), LV mass (r = 0.454,P-value =0.012)and LV mass index (r = 0.456,P-value =0.011). Conclusion:P wave dispersion and QT dispersion were prolonged in children with β-thalassemia major denoting cardiac autonomic dysfunction with homogeneity disorders of atrial conduction and ventricular repolarization in these patients

Left ventricular dysfunction by strain echocardiography in thalassemia patients: a pilot study

Background: To evaluate the myocardial function and its correlation with serum ferritin and the number of transfusions in beta-thalassemia major patients by using standard echocardiography and left ventricular strain imaging.Methods: This was a cross-sectional exploration study comprised of 56 beta-thalassemia patients conducted at a tertiary-care center in India between September 2016 and August 2017. Patients with age less than 18 years, diagnosed with thalassemia major, recipients of >20 units of blood transfusions, and normal Left Ventricular (LV) function by 2D-echocardiography were included in the study. Severity of iron overload was determined by using serum ferritin levels and LV strain imaging parameters were evaluated by using strain values of 17 LV segments.Results: A total of 56 beta-thalassemia patients were included in the study. Of these, 29(51.8%) patients were boys and 27(48.2%) patients were girls with a mean age of 7.8±1.84 years. Average serum ferritin level was found to be 4089.83 ng/dl. Strain values of the basal lateral wall of the left ventricle were significantly abnormal in patients who received more (>80) transfusions compared with those who received lesser transfusions (p=0.025 and p=0.045), respectively. Patients with serum ferritin >6000 ng/ml had impaired strain (p=0.03).Conclusions: Conventional echocardiographic parameters and Left Ventricular Ejection Fraction (LVEF) do not provide adequate information about LV dysfunction. Systolic strain index imaging of the LV indicated the presence of early LV systolic dysfunction in patients who received a greater number of blood transfusions and patients with higher serum ferritin levels.

Intraocular pressure in subjects with beta-thalassemia minor / Pressão intraocular em indivíduos com talassemia beta minor

ABSTRACT Purpose: Beta-thalassemia minor, a common hereditary blood disorder in Mediterranean countries such as Turkey, is associated with insulin resistance. Insulin resistance, in turn, can be associated with excessively high intraocular pressure and, therefore, intraocular pressure-induced blindness. This study aimed to investigate the intraocular pressure in subjects with beta-thalassemia minor. Methods: We conducted a cross-sectional study comprising of 203 subjects divided into two groups: beta-thalassemia minor (103) and healthy (100).Hemoglobin electrophoresis was performed and complete blood count, blood pressures, serum fasting glucose and insulin levels were measured. All subjects underwent ophthalmological examinations including intraocular pressure measurements. Results: Intraocular pressure in the subjects with beta-thalassemia minor was significantly lower than that in healthy subjects (p=0.007). Additionally, intraocular pressure was inversely correlated with hemoglobin A2 levels (p=0.001, r=-0.320). Serum insulin and systolic blood pressure were significantly higher in subjects with beta-thalassemia minor (p=0.03, p=0.009, respectively). Conclusion: Subjects with beta-thalassemia minor had lower intraocular pressure than healthy controls, suggesting beta-thalassemia minor may actually protect against high intraocular pressure.

RESUMO Objetivo: Beta-talassemia menor é uma doença hereditária comum no sangue em países mediterrâneos como a Turquia e está associada à resistência à insulina. A resistência à insulina por sua vez, pode estar associada à pressão intraocular excessivamente alta e, portanto à cegueira induzida pela pressão intraocular. Este estudo teve como objetivo investigar a pressão intraocular em indivíduos com beta-talassemia menor. Métodos: Foi realizado um estudo transversal compreendendo 203 indivíduos divididos em 2 grupos: beta-talassemia menor (103) e saudável (100). Eletroforese de hemoglobina foi realizada e hemograma completo, pressão arterial, glicemia em jejum e níveis de insulina medidos. Todos os indivíduos foram submetidos foram submetidos a exames oftalmológicos, incluindo medidas de pressão intraocular. Resultados: A pressão intraocular nos indivíduos com beta-talassemia menor foi significativamente menor do que em indivíduos saudáveis (p=0,007). Além disso, a pressão intraocular foi inversamente correlacionada com os níveis de hemoglobina A2 (p=0,001, r=-0,320). Insulina sérica e pressão arterial sistólica foram significativamente maiores em indivíduos com beta-talassemia menor (p=0,03, p=0,009, respectivamente). Conclusão: Os indivíduos com beta-talassemia menor tiveram pressão intraocular menor do que os controles saudáveis, sugerindo que a beta-talassemia menor pode, na verdade, proteger contra a alta pressão intraocular.

Echocardiografic abnormalities in patients with sickle cell/β thalassemia do not depend on the β-thalassemia phenotype

ABSTRACT Objectives and methods: We evaluated possible relationships between echocardiographic findings and clinical and laboratory parameters, in a cohort of Brazilian patients diagnosed with sickle cell/β-thalassemia, to better understand the cardiac involvement in this disease. Results: Left atrial (LA) and left ventricular (LV) dilation were found in 19.5 and 11% of patients, respectively; systolic left ventricular dysfunction was present in a single patient. There were no differences in masses and volumes of cardiac chambers comparing Sβ0 with Sβ+ patients, and no relationship between these parameters and specific complications of the disease. However, parameters of altered ventricular geometry were significantly correlated with serum creatinine, hepatic transaminases and bilirubin levels. Moreover, 3 patients presented stroke; they were significantly older [53 (41-56) × 37.5 (18-70), p = 0.048], had higher values of LV posterior wall diastolic thickness [10 (10-11) × 8 (6-14), p = 0.03], LV mass [226 (194-260) × 147 (69-537), p = 0.039] and LA/aortic ratio [1.545 (1.48-1.61) × 1.26 (0.9-1.48), p = 0.032]. Conclusions: Cardiac involvement in this disease does not appear to depend on the thalassemia phenotype. The presence of signs of myocardial remodeling in this group of patients was related to multi-organ impairment and rendered a higher propensity for stroke in older patients, suggesting the need for greater vigilance and control of associated factors.

Characterization of thalassemia major and diabetes mellitus patients at a reference center in Brazil

ABSTRACT Objective: This is a quantitative transversal study that aimed to analyze the sociodemographic and clinical characteristics of thalassemia major patients with and without diabetes mellitus. Method: The cohort consisted of 31 thalassemia major patients from a reference center of treatment in Brazil in 2016. The data were obtained from an interview using a questionnaire containing demographic and clinical variables. The results show that 16.1% of the participants with thalassemia major had diabetes mellitus. The participants' ages ranged from 20 to 48 years, with an average of 35 years, mostly students and starting in the formal job market. The most commonly used treatment was the oral desferasirox and the transfusion treatment interval was 15-22 days. Results: Patients with thalassemia major and diabetes mellitus presented altered values of fasting glycemia, serum alanine transaminase, magnetic resonance imaging and bone densitometry. Conclusion: It was concluded that knowledge of the characteristics of this population contributes in the proposal of effective educational strategies in light of the complexity of care and the progression of the disease.

Study of Ocular Manifestations among Beta Thalassemia Major Patients

Person with thalassemia major may have severe symptoms and may need regular blood transfusions. Iron overload is due to repeated blood transfusions and enhanced iron absorption by gastrointestinal tract and also creates negative impact on the organs function. We aimed to study the ocular changes in beta thalassemia major at a tertiary care hospital. Methods: In this prospective observational study, 234 patients diagnosed with beta thalassemia major, receiving multiple blood transfusions as a part of treatment were included. Patient brief history was taken, along with family history. Complete eye examination done. Ocular examination done by measuring visual acuity, refractive error assessment with autorefractometer, slit lamp examination, fundoscopy, perimetry, tonometry, color vision testing and tear break up time (TBUT) test. Results: A total of 234 beta thalassemia major patients of both sexes were evaluated, among them 132 (56.4%) were males and 102 (43.5%)were females. The mean age of thalassemic study population was 25.6±6.3. Most commonly observed were pinguecula (44%), visual field defects (40.5%), vascular tortuosity (39.3%), dry eye (33.3%), Refractive error (20.5%), Anterior segment involvement (18.8%), Cataract (13.2%), color vision defect (5.1%), normalization of optical vessels (4%). Conclusion: Regular Opthalmological examination helps to detect early changes due to disease and chelating agents. Issue of iron overload among thalassemic patients can be reduced by decreasing the need or the frequency of blood transfusions.

Renal Iron Load Estimation in Thalassemia Patients Using T2* Magnetic Resonance Imaging

Purpose: Multi-organ hemosiderosis is a known complication in thalassemia patients with chronic blood transfusion. T2-Star (T2*) MRI has been introduced as a non-invasive tool for detecting iron overload in the liver and heart in these patients. This study is to determine and assess renal iron overload by MRI and its relation to liver and heart iron and serum ferritin in Iranian thalassemia patients. Methods: Total 821 transfusion dependent major and intermediate thalassemia patients (age range 10-50 years) were included in this study and calculations were done on their MRI data in a medical imaging center through 2014-2016. Iron values were calculated and averaged in a different region of interests (ROI) using fast-gradient-echo multi-echo T2* sequences. Results: Pathological renal iron content less than 36 ms was around 19.6%. The mean T2* kidney of the total population was 50.26 ms. A moderate negative, statistically significant correlation between kidney T2* relaxation time and serum ferritin was noted. For liver and heart, T2* relaxation time weakly, a statistically significant correlation was acquired by renal T2* relaxation time. Conclusions: Renal hemosiderosis was shown in numerous thalassemia patients. Since the frequency of renal iron deposition was approximately 20% in TM patients in a general population study, it might shed light that frequently monitors the renal iron loading merit hematologists in preventing the secondary side effects.