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.

Human leukocyte antigen immunization in transfusion-dependent Moroccan patients with beta-thalassemia major: prevalence and risk factors.

INTRODUCTION: Beta-thalassemia major patients need a regular blood transfusion to have an initial normal growth. However, these patients have an increased risk of developing alloantibodies. Our main goal was to study HLA alloimmunization in Moroccan Beta-thalassemia patients by confronting it with transfusion and demographic criteria, exploring the involvement of HLA typing profile in the development of HLA antibodies and in turn determining risk factors for their development. METHODS: The study consisted of 53 Moroccan pediatric patients with Beta-thalassemia major. Screening for HLA alloantibodies was performed using Luminex technology Whereas HLA genotyping was done with sequence-specific primers (PCR-SSP). RESULTS: In this study, 50.9% of patients have been identified as positive for HLA antibodies, with 59.3% having both HLA Class I and Class II antibodies. A significant increase frequency of DRB1*11 allele was revealed in non-immunized patients (34.6% vs. 0%, p = 0.001). Our results also revealed that the majority of our HLA immunized patients were women (72.4% vs. 27.6%, p = 0.001), and transfused with more than 300 units of RBC units (66.7% vs. 33.3%, p = 0.02). There were statistically significant differences when comparing these frequencies. CONCLUSIONS: This paper revealed that the transfusion dependent Beta-thalassemia major patients are exposed to risk of developing HLA antibodies following transfusions with leukoreduced RBC units. The HLA DRB1*11 was a protective factor against HLA alloimmunization in our beta-thalassemia major patients.

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

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)

Molecular and Hematological Analysis of Alpha- and Beta-Thalassemia in a Cohort of Mexican Patients.

Introduction: Alpha- and beta-thalassemia are caused by reduced or absent synthesis of hemoglobin (Hb) subunits α and/or ß. HBA2, HBA1, and HBB mutations are the main cause of thalassemias. The aim of this article is to analyze molecular and hematological features of α- and ß-thal in a cohort of Mexican patients. Methods: One hundred forty-one thalassemia patients were studied. Peripheral blood was collected for blood cell count, electrophoresis, Hb quantification, and molecular testing. Molecular screening was performed by Gap-PCR, ARMS-PCR, Sanger sequencing, and MLPA. Results: Fifty-four patients had α-thal, 75 ß-thal, and 12 patients were complex cases, we observed 13 α- and 18 ß-thal alleles in 43 genotypes, -α3.7/αα and ßCd39C>T/ß were the most frequent. Four α-thal deletions (-Mex4 included HBA2 and HBA1, whereas (αα)Mex5, Mex6 and Mex7 involved MCS-R), a hereditary persistence of fetal hemoglobin-2 like (HPFH-2 like) deletion and six alleles not previously reported in Mexicans (α-59C>Tα, -α4.2, αPlasenciaα, ß-32C>T, ßInitCdA>C and ßFSCd71/72+A) were identified. Conclusion: The observed alleles denote the high heterogeneity and multiple origin admixture of Mexican population. Hematological data are consistent with genotypes, variability in simple carriers, from asymptomatic forms to mild or moderate anemia, was ascertained. We emphasize the importance to consider hematological parameters to establish adequate molecular screening strategies.

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.

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.

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.

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.

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.

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

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.

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

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/ß-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 Sß0 with Sß+ 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.

Beta-Talasemia: Un mundo de complicaciones con nuevas alternativas de tratamiento / Beta-Thalassemia: A world of complications with new alternatives of treatment

Introducción: ß-talasemia, es causada por mutaciones en el gen de la globina HBB, que codifica la subunidad ß de la HbA. La enfermedad es conocida por ser altamente prevalente en el área que se extiende desde África subsahariana, a través de la región mediterránea y Medio Oriente. En Colombia, se han reportado varios estudios independientes de hemoglobinopatías en ciudades como Cartagena, Buenaventura, Cali, San Andrés y Providencia debido a su gran población afrodescendiente sobre la cual las Talasemias y otras hemoglobinopatías tienen incidencia directa. Objetivo: recolectar datos acerca de las características clínicas, complicaciones y clasificaciones de ß-talasemia con el fin de brindar una fuente de información que permita realizar un diagnóstico eficaz y en consecuencia un tratamiento que busque llegar a la curación completa de los pacientes que sufren esta condición, con el mínimo de complicaciones para los mismos. Conclusión: la ß-Talasemia es una hemoglobinopatía estructural que tiene un porcentaje de prevalencia e incidencia importante en el mundo. En Colombia no se tiene claro cuál es la epidemiología real para esta condición puesto que no se han realizado estudios que abarquen una muestra adecuada y significativa. Esta enfermedad genera múltiples complicaciones en diferentes órganos, que no solo están asociadas al desarrollo de la enfermedad, sino también a la terapia de trasfusión a largo plazo. Por esta razón, los nuevos tratamientos están encaminas a lograr en un futuro la curación completa, reduciendo al máximo las complicaciones..(AU)

Introduction: ß-thalassemia is caused by mutations in the HBB globin gene, which encodes the ß subunit of HbA. The disease is known to be highly prevalent in the area that stretches from sub-Saharan Africa, through the Mediterranean region and the Middle East. In Colombia, several independent studies of hemoglobinopathies have been reported in cities such as Cartagena, Buenaventura, Cali, San Andrés and Providencia due to their large Afro-descendant population on wich the thalassemias and other hemoglobinopathies.have direct incidence. Objective: to collect data about the clinical characteristics, complications and classifications of ß-thalassemia in order to provide a source of information that allows an effective diagnosis and a treatment that seeks to reach the complete cure of patients that have this condition. , with the minimum of complications for them. Conclusion: ß-thalassemia is a structural hemoglobinopathy that has a percentage of prevalence and incidence important in the world. In Colombia it is not clear what is the real epidemiology for this condition that has not been conducted studies that include an adequate and significant sample.This disease generates multiple complications in different organs, but not only in long-term transfusion therapy. For this reason, the new treatments are aimed at achieving complete healing in the future, minimizing complications at maximum..(AU)

Prevalência de hemoglobinopatias na população adulta brasileira: Pesquisa Nacional de Saúde 2014-2015 / Prevalence of hemoglobinopathies in the Brazilian adult population: National Health Survey 2014-2015

RESUMO: Objetivo: Descrever a prevalência das hemoglobinopatias da população adulta brasileira, segundo exames laboratoriais da Pesquisa Nacional de Saúde. Métodos: Estudo descritivo realizado com os dados laboratoriais da Pesquisa Nacional de Saúde coletados entre os anos de 2014 e 2015. A pesquisa de hemoglobinopatias foi feita pelo método da cromatografia líquida de alto desempenho. Os resultados dos exames individuais foram interpretados fornecendo os parâmetros normais, homozigotos ou heterozigotos para hemoglobina S, C e D, além de outras eventuais hemoglobinopatias. Foram estimadas prevalências das hemoglobinopatias segundo sexo, cor da pele, região, idade e escolaridade. Resultados: Houve presença de hemoglobinopatias em 3,7% da população. As principais foram o traço falciforme (2,49%), a talassemia menor (0,30%) e a suspeita de talassemia maior (0,80%). Em relação ao traço falciforme e à suspeita de talassemia maior, houve diferença estatisticamente significativa para a variável cor da pele (p < 0,05). As prevalências encontradas para traço falciforme segundo cor de pele foram: preta (4,1%), parda (3,6%), branca (1,2%) e outras (1,7%). Conclusão: As hemoglobinopatias mais prevalentes foram o traço falciforme e a talassemia menor, predominando entre pretos e pardos. O estudo ajuda na identificação das hemoglobinopatias e no aconselhamento genético na preconcepção.

ABSTRACT: Objective: To describe the prevalence of hemoglobinopathies in the Brazilian adult population, according to laboratory tests from the National Health Survey. Methods: A descriptive study was carried out with National Health Survey laboratory data collected between 2014 and 2015. The hemoglobinopathies test was performed using the High Performance Liquid Chromatography method. The results of the individual tests were interpreted as providing normal, homozygous or heterozygous results for S, C and D hemoglobin, in addition to other possible hemoglobinopathies. Prevalence of hemoglobinopathies according to gender, skin color, region, age and schooling was estimated. Results: Hemoglobinopathies were present in 3.7% of the population. The main ones were the sickle cell trait (2.49%), thalassemia minor (0.30%) and suspected thalassemia major (0.80%). In relation to the sickle cell trait and suspected thalassemia major, there was a statistically significant difference for the skin color variable (p<0.05). The prevalences found for sickle cell trait according to skin color was: 4.1% among dark-skinned blacks, 3.6% among light-skinned blacks, 1.2% among whites, and 1.7% among others. Conclusion: The most prevalent hemoglobinopathies were the sickle cell trait and minor thalassemia, and were predominate among light- and dark-skinned black people. The study helps in identifying hemoglobinopathies and in genetic counseling in pre-conception.

Two novel unstable hemoglobin variants due to in-frame deletions of key amino acids in the ß-globin chain.

Hemoglobinopathies are the most common autosomal recessive disorders and are mostly inherited in a recessive manner. However, certain mutations can affect the globin chain stability, leading to dominant forms of thalassemia. The aim of this work was the molecular and structural characterization of two heterozygous in-frame deletions, leading to ß-globin variants in pediatric patients in Argentina. The HBB gene of the probands and their parents was sequenced, and other markers of globin chain imbalance were analyzed. Several structural analyses were performed, and the effect of the mutations on the globin chain stability was analyzed. In Hb JC-Paz, HBB:c.29_37delCTGCCGTTA (p.Ala10_Thr12del), detected in an Argentinean boy, one α-helix turn is expected to be lost. In Hb Tavapy, HBB:c.182_187delTGAAGG (p.Val60_Lys61del), the deleted residues are close to distal histidine (His63) in the heme pocket. Both mutations are predicted to have a destabilizing effect. The development of computational structural models and bioinformatics algorithms is expected to become a useful tool to understand the impact of the mutations leading to dominant thalassemia.

Frequencies of CD39, IVS1-1, IVS1-6 and IVS1-110 mutations in beta-thalassemia carriers and their influence on hematimetric indices / Frequências de mutações CD39, IVS1-1, IVS1-6 e IVS1-110 em portadores de betatalassemia e suas influências nos valores hematimétricos

ABSTRACT Introduction: Beta-thalassemia is caused by a deficient synthesis of the ß-chain of hemoglobin, which leads to a chronic, microcytic and hypochromic anemia. More than 200 mutations have already been associated with this type of thalassemia, and their frequencies may vary according to the population. Objectives: The objectives of this study were to determine the frequencies of CD39, IVS1-1, IVS1-6 and IVS1-110 mutations in people with beta-thalassemia from the city of Franca, São Paulo, and to evaluate the influence of the genotypes on hematological alterations. Methods: Venous blood samples were collected from 25 volunteers previously diagnosed with beta-thalassemia. Complete blood counts (CBC) were performed, and the identification of the mutations was carried out using the polymerase chain reaction (PCR). Results: The CD39 mutation was found in 11 (44%) individuals, followed by IVS1-6 (9; 36%) and IVS1-110 (4; 16%). One patient (4%) did not present any of these mutations. IVS1-6 mutation was inversely correlated to red cell distribution width (RDW) (rs = -0.44; p = 0.034), and CD39 was correlated to lower mean corpuscular volume (MCV) (rs = -0.44; p = 0.034). Multivariable linear regression models showed that the CD39 mutation carriers have lower levels for hemoglobin (ß = -0.61; p = 0.044) and hematocrit (ß = -2.1; p = 0.018). Conclusion: The results showed a high frequency of the CD39 mutation in the city of Franca, and the correlations observed between the presence of CD39 mutation and the hematological alterations suggest a genotype influence on the phenotype of beta-thalassemia, which would contribute to the clinical variations of this hemoglobinopathy.

RESUMO Introdução: A betatalassemia é causada pela síntese deficiente da cadeia ß da hemoglobina, o que leva à ocorrência das anemias crônica, microcítica e hipocrômica. Mais de 200 mutações já foram associadas a esse tipo de talassemia, mesmo que diferentes populações apresentem frequências variadas para cada uma delas. Objetivos: Os objetivos deste estudo foram determinar as frequências das mutações CD39, IVS1-1, IVS1-6 e IVS1-110 em indivíduos betatalassêmicos da cidade de Franca, São Paulo, e avaliar a influência dos genótipos sobre alterações hematológicas. Métodos: Amostras de sangue venoso foram coletadas de 25 voluntários previamente diagnosticados com betatalassemia. Foram realizados hemogramas completos, e a identificação das mutações foi feita utilizando a técnica de reação em cadeia da polimerase (PCR). Resultados: A mutação CD39 foi encontrada em 44% dos indivíduos, seguida por IVS1-6 (36%) e IVS1-110 (16%). Um paciente (4%) não apresentou nenhuma das mutações. A mutação IVS1-6 correlacionou-se inversamente ao red cell distribution width (RDW) (rs = -0,44; p = 0,034), enquanto a presença da mutação CD39 mostrou-se correlacionada a menores valores de volume corpuscular médio (VCM) (rs = -0,44; p = 0,034). Modelos de regressão linear multivariados mostraram que os portadores da mutação CD39 possuem menores valores de hemoglobina (ß = -0,61; p = 0,044) e hematócrito (ß = -2,1; p = 0,018). Conclusão: Os resultados mostraram alta frequência da mutação CD39 na cidade de Franca, e as correlações observadas entre a presença da mutação CD39 e as alterações hematológicas sugerem influência do genótipo sobre o fenótipo da betatalassemia, o que poderia contribuir para as variações clínicas dessa hemoglobinopatia.