Association of ZBTB38 gene polymorphism (rs724016) with height and fetal hemoglobin in individuals with sickle cell anemia.

Objectives: Our study evaluated the association of the polymorphism rs724016 in the ZBTB38 gene, previously associated with height in other populations, with predictors of height, clinical outcomes, and laboratory parameters in sickle cell anemia (SCA). Methods: Cross-sectional study with individuals with SCA and aged between 3 and 20 years. Clinical, laboratory, molecular, and bone age (BA) data were evaluated. Levels of IGF-1 and IGFBP-3 were adjusted for BA, target height (TH) was calculated as the mean parental height standard deviation score (SDS), and predicted adult height (PAH) SDS was calculated using BA. Results: We evaluated 80 individuals with SCA. The homozygous genotype of the G allele of rs724016 was associated with a lower height SDS (p < 0.001) and, in a additive genetic model, was negatively associated with HbF levels (p = 0.016). Lower adjusted IGF-1 levels were associated with co-inheritance of alpha-thalassemia and with the absence of HU therapy. Elevated HbF levels were associated with a lower deficit in adjusted growth potential (TH minus PAH). Conclusion: Our analysis shows that SNP rs724016 in the ZBTB38 is associated with shorter height and lower HbF levels, an important modifier of SCA.

Clinical, laboratory, and molecular characteristics of a cohort of children with hemoglobinopathy S/beta-thalassemia.

INTRODUCTION: Hemoglobinopathy Sß-thalassemia (HbSß-thal) has a wide range of clinical and laboratory severity. There is limited information on the natural history of HbSß-thal and its modulating factors. We described the molecular, hematological, and clinical characteristics of a cohort of children with HbSß-thal and estimated its incidence in Minas Gerais, Brazil. METHODS: Laboratory and clinical data were retrieved from medical records. Molecular analysis was performed by HBB gene sequencing, PCR-RFLP, gap-PCR, and MLPA. RESULTS: Eighty-nine children were included in the study. Fourteen alleles of ß-thal mutations were identified. The incidence of HbSß-thal in the state was 1 per 22,250 newborns. The most common ßS-haplotypes were CAR and Benin. The most frequent ßthal-haplotypes were V, II, and I. Coexistence of 3.7 kb HBA1/HBA2 deletion was present in 21.3 % of children. ß-thalassemia mutations were associated with several clinical and laboratory features. In general, the incidence of clinical events per 100 patient-years was similar for children with HbSß0-thal, IVS-I-5 G>A, and IVS-I-110 G>A. Children with HbSß+-intermediate phenotypes had a more severe laboratory and clinical profile when compared with those with HbSß+-mild ones. ßS-haplotypes and α-thalassemia did not meaningfully influence the phenotype of children with HbSß-thal. CONCLUSION: The early identification of ß-thalassemia alleles may help the clinical management of these children.

CETP gene polymorphisms and haplotypes are explanatory variables for HDL cholesterol level in sickle cell disease

Variations in lipid profile have been observed in sickle cell disease (SCD) and understanding their relationship with disease severity is crucial. This study aimed to investigate the association of polymorphisms of the CETP gene and laboratory markers of disease severity with lipid profile in a pediatric population with SCD. Biochemical and anthropometric analyses and CETP and alpha-thalassemia genotyping were performed. The study included 133 children and adolescents with sickle cell anemia (SCA) or hemoglobin SC disease (SCC), in steady-state. The SCA and no hydroxyurea (no HU) groups had higher values of ApoB, total cholesterol, low-density lipoprotein cholesterol (LDL-C), and non-high-density lipoprotein cholesterol (non-HDL-C) compared to the SCC and HU groups. However, there were no significant differences in ApoA1 and HDL-C levels between the groups based on genotype. Furthermore, the groups with altered levels of ApoA1, HDL-C, and the triglyceride/HDL ratio exhibited lower hemoglobin (Hb) levels and higher white blood cell counts. Hb level was associated to HDL-C levels. Analysis of CETP gene variants showed that the minor alleles of rs3764261 (C>A), rs247616 (C>T), and rs183130 (C>T), as well as the TTA haplotype, are explanatory variables for HDL-C levels. These findings suggested that dyslipidemia in SCD, specifically related to HDL-C levels, may be influenced by individual genetic background. Additionally, further investigation is needed to determine if clinical manifestations are impacted by CETP gene variants.

Clinical, laboratory, and molecular characteristics of a cohort of children with hemoglobinopathy S/betathalassemia

ABSTRACT Introduction: Hemoglobinopathy Sβ-thalassemia (HbSβ-thal) has a wide range of clinical and laboratory severity. There is limited information on the natural history of HbSβ-thal and its modulating factors. We described the molecular, hematological, and clinical characteristics of a cohort of children with HbSβ-thal and estimated its incidence in Minas Gerais, Brazil. Methods: Laboratory and clinical data were retrieved from medical records. Molecular analysis was performed by HBB gene sequencing, PCR-RFLP, gap-PCR, and MLPA. Results: Eighty-nine children were included in the study. Fourteen alleles of β-thal mutations were identified. The incidence of HbSβ-thal in the state was 1 per 22,250 newborns. The most common βS-haplotypes were CAR and Benin. The most frequent βthal-haplotypes were V, II, and I. Coexistence of 3.7 kb HBA1/HBA2 deletion was present in 21.3 % of children. β-thalassemia mutations were associated with several clinical and laboratory features. In general, the incidence of clinical events per 100 patient-years was similar for children with HbSβ0-thal, IVS-I-5 G>A, and IVS-I-110 G>A. Children with HbSβ+-intermediate phenotypes had a more severe laboratory and clinical profile when compared with those with HbSβ+-mild ones. βS-haplotypes and α-thalassemia did not meaningfully influence the phenotype of children with HbSβ-thal. Conclusion: The early identification of b-thalassemia alleles may help the clinical management of these children. © 2023 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U. This is an open access article under the CC BY-NC-ND license

Lipids profile in children and adolescents with b-thalassemia major

ABSTRACT Introduction: Patients with β-thalassemia major (β-TM) are at risk of developing abnormal lipid profiles. Lipid abnormalities, in turn, have a potential role in the pathogenesis of some clinical aspects of thalassemia Objectives: To evaluate lipid levels and atherogenic indices in β-TM patients compared to healthy children and for any association between lipid levels, lipid peroxidation and inflammatory biomarkers Methods: This case-control study was carried out on 79 patients with β-TM, aged 6 to 16 years, registered at the Basrah Center for Hereditary Blood Diseases and 85 age- and sex-matched apparently healthy children and adolescents. Complete blood count, serum lipids and ferritin, liver function tests, C-reactive protein (CRP), high-sensitivity CRP (hs-CRP) and serum malondialdehyde (MDA) were evaluated Results: Patients with β-TM had significantly lower hemoglobin (Hb), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) and significantly higher very low-density lipoprotein (VLDL), triglycerides (TGs), LDL/HDL ratio, MDA, hs-CRP, total serum bilirubin (TSB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group (p < 0.05). A bivariate analysis revealed that TC has a significant positive association with Hb. The TG has a significant negative association with Hb and a positive association with serum ferritin. Furthermore, MDA, TG, TSB, ALT and AST were significantly positively correlated with serum ferritin (p < 0.05) Conclusions: Atherogenic dyslipidemia, defined as a high low-density lipoprotein cholesterol (LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio and high TG level, is common among pediatric β-TM patients, it is associated with iron overload and places patients at an increased cardiovascular risk.

Extramedullary haematopoiesis in patients with thalassemia: a cross-sectional description of its prevalence, clinical features and survival.

INTRODUCTION: Despite knowledge advances on extramedullary haematopoiesis (EMH) in thalassemic patients, the real picture remains an open issue. OBJECTIVES: To assess EMH prevalence in patients with thalassemia major (TM) and intermedia (TI), to describe magnetic resonance imaging (MRI) findings and to explore clinical risk factors. METHODS: In this cross-sectional study, images and clinical records of 184 consecutive patients with thalassemia who underwent T2* MRI between 2004 and 2011 were reviewed. Association of EMH with survival was investigated for patients with available follow-up charts. RESULTS: EMH was detected in 16/168 (9.5%) patients with TM (aged 19-49 years) and in 3/16 (18.8%) with TI (aged 36-41 years). Most (88%) had paravertebral thoracic and/or abdominal masses. Age was significantly associated with EMH risk (hazard ratio, [HR] 1.10/year; confidence interval [CI]: 1.03-1.18; p-value < 0.001), while lower pancreatic iron content by T2*MRI (HR: 0.94/ms; CI: 0.89-0.99; p-value = 0.049) was a protective factor. Estimated survival rate was superior for EMH-positive (n = 19) when compared to EMH-negative patients (n = 75) (p-value = 0.013). CONCLUSIONS: The prevalence of EMH was 10.3% (19/184), presented mainly as tumoral masses of 3 to 10 cm. Age was a risk factor for EMH development, while lower pancreatic iron might be a protective factor in this cohort.

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.

Genetic analysis of TMPRSS6 catalytic domain variants in Mexican patients with iron treatment refractoriness.

OBJECTIVE: To identify the TMPRSS6 gene variants in Mexican patients with iron treatment refractoriness, to describe hematological and iron profile parameters, and to use bioinformatic prediction and protein modeling tools to assess a possible biological impact for the detected missense variants. METHODS: Nineteen patients referred with iron treatment refractoriness were studied. Peripheral blood was collected to determine hematic cytometry, iron profile, hemoglobin electrophoresis, and quantification. Molecular screening was carried out for exons 15 through 18 of the TMPRSS6 gene by Sanger sequencing and for frequent thalassemia variants by amplification-refractory mutation system-polymerase chain reaction (PCR) and gap-PCR. The biological impact of the detected missense variants was assessed using bioinformatic prediction and protein modeling tools. RESULTS: We found 5 genetic variants in the matriptase-2 catalytic domain: 1 at intron-15/exon-16 junction (rs60484081) and 4 exonic, 3 missense (rs377054987, p.Gly626Asp; rs1384127820, p.Ser672Thr; rs855791, p.Val727Ala) and 1 synonymous (rs2235321, p.Tyr730=), with frequencies ranging from 0.18 to 0.53. No significant differences were observed in the hematological parameters or iron profile, considering type and number of variants. Bioinformatic predictions suggested a possible biological impact only for rs377054987. CONCLUSIONS: The TMPRSS6 variants observed in Mexican patients with oral iron treatment refractoriness have high frequencies; nevertheless, their relationship with hematological and iron profile parameters needs further research. The possible biological impact for rs377054987 is due to size and amino acid hydrophobicity changes and hydrogen bond modifications.

Differences in the distribution of hemoglobin variants according to the geographic regions in a Colombian population

ABSTRACT Introduction: Colombia has been subject to intense genetic and cultural currents due to its geographical location. Hemoglobinopathies are the most common recessive diseases found worldwide and represent an important public health problem, according to the region and ancestry of each country. Objectives: To evaluate the frequency of hemoglobin variants according to the geographical region in a population group adjusted to sex and age in Colombia. Methods: This was a descriptive retrospective study of hemoglobin variants performed by electrophoresis in patients treated at and/or referred to specialized care institutions in Bogota, Colombia between January 2009 and December 2020. Results: A total of 2,224 results were analyzed, 48.4% male and 51.5% female; 63.3% of patients were without alterations, 14.3% presented with thalassemia, 17.3%, HbS, 2.3%, HbS/C, 1.8%, HbC, 0.5%, HbE and 0.5% persistent HbF, with HbS being more prevalent in males (p = 0.005). When assessing the geographical regions of Colombia, a higher prevalence of HbS was found in the Pacific (p = 0.005) and Caribbean regions, while Thalassemia and HbS were more prevalent in the Andean and Orinoquia regions, and it was rare to find any hemoglobinopathies (p = 0.0001) in the Amazonian region. Conclusions: The main hemoglobinopathies found in Colombia are HbS, predominantly in males, and Thalassemia. The distribution of hemoglobinopathies in different geographical regions of Colombia is influenced by ancestry.

Unusual Association of Intestinal Tuberculosis and Thalassemia: A Case Report

Introduction: Tuberculosis is an infectious disease that can be prevented and cured, but it is still associated with high morbidity and mortality rates. Disseminated tuberculosis, although rare, can occur in individuals with underlying pathologies that affect the immune system. Currently, there are limited reports on disseminated tuberculosis in individuals with congenital disorders. Clinical case: We present a case of a patient with a history of ß thalassemia who was admitted to the emergency department with symptoms of abdominal pain and constitutional symptoms. The final diagnosis was disseminated tuberculosis. This case is of particular interest due to its atypical presentation, the initial suspicion of malignancy, and the extensive involvement of the disease despite the patient's absence of immunosuppression history. Conclusions: Disseminated tuberculosis in immunocompetent patients is a rare presentation associated with poor outcomes. The history of ß thalassemia may be a risk factor to consider based on the metabolic pathways involved in the pathophysiology of both diseases.

Introducción: la tuberculosis es una enfermedad infecciosa prevenible y curable asociada a una alta morbimortalidad, la presentación de tuberculosis diseminada es poco frecuente y está asociada a patologías que comprometen el sistema inmunitario. En la actualidad hay pocos informes sobre tuberculosis diseminada y trastornos congénitos subyacentes. Caso clínico: paciente con antecedente de talasemia ß que ingresó al servicio de urgencias por dolor abdominal y síntomas constitucionales con diagnóstico final de tuberculosis diseminada. Es un caso de especial interés debido a la presentación atípica, la sospecha diagnóstica inicial de malignidad y el amplio compromiso de la enfermedad a pesar de que el paciente no tenía antecedentes de inmunosupresión. Conclusiones: la tuberculosis diseminada en el paciente inmunocompetente es una presentación poco frecuente asociada a desenlaces adversos. El antecedente de talasemia ß podría ser un factor de riesgo para tener en cuenta con base en las vías metabólicas involucradas en la fisiopatología de ambas enfermedades.

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.

Dyslipidemia and atherogenic indexes in children with transfusion-dependent thalassemia.

OBJECTIVE: This study endeavored to assess the lipid profile and atherogenic lipid indexes in children with transfusion-dependent thalassemia (TDT) and to compare them with matched healthy children. METHOD: The study group consisted of a total of 72 TDT patients aged 3 to14 years, while the control group had 83 age- and sex-matched healthy children. The fasting lipid profile and lipid indexes were estimated and the atherogenic index of plasma (AIP), Castelli's risk indexes I and II, atherogenic coefficient were calculated and compared between the two groups. RESULT: Compared to the control group, the mean LDL, HDL and cholesterol levels were significantly lower among the case group (p-value < 0.001). The mean VLDL and triglycerides were significantly higher in the case group (p-value < 0.001). Lipid indexes, including the atherogenic index of plasma (AIP), Castelli's risk indexes I and II and atherogenic coefficients were significantly higher in TDT children. CONCLUSION: Dyslipidemia and increased risk of atherosclerosis were found in TDT children, as they had elevated atherogenic lipid indexes. Our study underlines the importance of the routine use of these indexes in TDT children. Future studies should focus on lipid indexes in this high-lipid group of children so that preventive strategies can be planned accordingly.

Cardiac iron overload evaluation in thalassaemic patients using T2* magnetic resonance imaging following chelation therapy: a multicentre cross-sectional study

Abstract Introduction Magnetic resonance imaging (MRI) T2* technique is used to assess iron overload in the heart, liver and pancreas of thalassaemic patients. Optimal iron chelation and expected tissue iron response rates remain under investigation. The objective of this study was to analyse serum ferritin and the iron concentration in the heart, liver and pancreas measured by MRI T2*/R2* during regular chelation therapy in a real-world cohort of patients with thalassemia. Methods We evaluated thalassaemic patients ≥ 7 years old undergoing chelation/transfusion therapy by MRI and assessed serum ferritin at baseline and follow-up from 2004-2011. Results We evaluated 136 patients, 92% major thalassaemic, with a median age of 18 years, and median baseline ferritin 2.033ng/ml (range: 59-14,123). Iron overload distribution was: liver (99%), pancreas (74%) and heart (36%). After a median of 1.2 years of follow-up, the iron overload in the myocardium reduced from 2,63 Fe mg/g to 2,05 (p 0.003). The optimal R2* pancreas cut-off was 148 Hertz, achieving 78% sensitivity and 73% specificity. However, when combining the R2* pancreas cut off ≤ 50 Hertz and a ferritin ≤ 1222 ng/ml, we could reach a negative predictive value (NPV) of 98% for cardiac siderosis. Only 28% were undergoing combined chelation at baseline assessment, which increased up to 50% on follow up evaluation. Conclusions Chelation therapy significantly reduced cardiac siderosis in thalassaemic patients. In patients with moderate/severe liver iron concentration undergoing chelation therapy, ferritin levels and myocardium iron improved earlier than the liver siderosis.

Differences in the distribution of hemoglobin variants according to the geographic regions in a Colombian population.

INTRODUCTION: Colombia has been subject to intense genetic and cultural currents due to its geographical location. Hemoglobinopathies are the most common recessive diseases found worldwide and represent an important public health problem, according to the region and ancestry of each country. OBJECTIVES: To evaluate the frequency of hemoglobin variants according to the geographical region in a population group adjusted to sex and age in Colombia. METHODS: This was a descriptive retrospective study of hemoglobin variants performed by electrophoresis in patients treated at and/or referred to specialized care institutions in Bogota, Colombia between January 2009 and December 2020. RESULTS: A total of 2,224 results were analyzed, 48.4% male and 51.5% female; 63.3% of patients were without alterations, 14.3% presented with thalassemia, 17.3%, HbS, 2.3%, HbS/C, 1.8%, HbC, 0.5%, HbE and 0.5% persistent HbF, with HbS being more prevalent in males (p = 0.005). When assessing the geographical regions of Colombia, a higher prevalence of HbS was found in the Pacific (p = 0.005) and Caribbean regions, while Thalassemia and HbS were more prevalent in the Andean and Orinoquia regions, and it was rare to find any hemoglobinopathies (p = 0.0001) in the Amazonian region. CONCLUSIONS: The main hemoglobinopathies found in Colombia are HbS, predominantly in males, and Thalassemia. The distribution of hemoglobinopathies in different geographical regions of Colombia is influenced by ancestry.

Cardiac iron overload evaluation in thalassaemic patients using T2* magnetic resonance imaging following chelation therapy: a multicentre cross-sectional study.

INTRODUCTION: Magnetic resonance imaging (MRI) T2* technique is used to assess iron overload in the heart, liver and pancreas of thalassaemic patients. Optimal iron chelation and expected tissue iron response rates remain under investigation. The objective of this study was to analyse serum ferritin and the iron concentration in the heart, liver and pancreas measured by MRI T2*/R2* during regular chelation therapy in a real-world cohort of patients with thalassemia. METHODS: We evaluated thalassaemic patients ≥ 7 years old undergoing chelation/transfusion therapy by MRI and assessed serum ferritin at baseline and follow-up from 2004-2011. RESULTS: We evaluated 136 patients, 92% major thalassaemic, with a median age of 18 years, and median baseline ferritin 2.033ng/ml (range: 59-14,123). Iron overload distribution was: liver (99%), pancreas (74%) and heart (36%). After a median of 1.2 years of follow-up, the iron overload in the myocardium reduced from 2,63 Fe mg/g to 2,05 (p 0.003). The optimal R2* pancreas cut-off was 148 Hertz, achieving 78% sensitivity and 73% specificity. However, when combining the R2* pancreas cut off ≤ 50 Hertz and a ferritin ≤ 1222 ng/ml, we could reach a negative predictive value (NPV) of 98% for cardiac siderosis. Only 28% were undergoing combined chelation at baseline assessment, which increased up to 50% on follow up evaluation. CONCLUSIONS: Chelation therapy significantly reduced cardiac siderosis in thalassaemic patients. In patients with moderate/severe liver iron concentration undergoing chelation therapy, ferritin levels and myocardium iron improved earlier than the liver siderosis.

Lipids profile in children and adolescents with ß-thalassemia major.

INTRODUCTION: Patients with ß-thalassemia major (ß-TM) are at risk of developing abnormal lipid profiles. Lipid abnormalities, in turn, have a potential role in the pathogenesis of some clinical aspects of thalassemia OBJECTIVES: To evaluate lipid levels and atherogenic indices in ß-TM patients compared to healthy children and for any association between lipid levels, lipid peroxidation and inflammatory biomarkers METHODS: This case-control study was carried out on 79 patients with ß-TM, aged 6 to 16 years, registered at the Basrah Center for Hereditary Blood Diseases and 85 age- and sex-matched apparently healthy children and adolescents. Complete blood count, serum lipids and ferritin, liver function tests, C-reactive protein (CRP), high-sensitivity CRP (hs-CRP) and serum malondialdehyde (MDA) were evaluated RESULTS: Patients with ß-TM had significantly lower hemoglobin (Hb), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) and significantly higher very low-density lipoprotein (VLDL), triglycerides (TGs), LDL/HDL ratio, MDA, hs-CRP, total serum bilirubin (TSB), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group (p < 0.05). A bivariate analysis revealed that TC has a significant positive association with Hb. The TG has a significant negative association with Hb and a positive association with serum ferritin. Furthermore, MDA, TG, TSB, ALT and AST were significantly positively correlated with serum ferritin (p < 0.05) CONCLUSIONS: Atherogenic dyslipidemia, defined as a high low-density lipoprotein cholesterol (LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio and high TG level, is common among pediatric ß-TM patients, it is associated with iron overload and places patients at an increased cardiovascular risk.

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.

Novel Decision Tool for More Severe α-Thalassemia Genotypes Screening with Functional Loss of Two or More α-Globin Genes: A Diagnostic Test Study.

After the exclusion of iron deficiency and ß-thalassemia, molecular research for α-thalassemia is recommended to investigate microcytic anemia. Aiming to suggest more efficiently the molecular analysis for individuals with a greater chance of having a symptomatic form of the disease, we have developed and validated a new decision tool to predict the presence of two or more deletions of α-thalassemia, increasing considerably the pre-test probability. The model was created using the variables: the percentage of HbA2, serum ferritin and mean corpuscular volume standardized by age. The model was trained in 134 patients and validated in 160 randomly selected patients from the total sample. We used Youden's index applied to the ROC curve methodology to establish the optimal odds ratio (OR) cut-off for the presence of two or more α-globin gene deletions. Using the OR cut-off of 0.4, the model's negative predictive value (NPV) was 96.8%; the cut-off point accuracy was 85.4%; and the molecular analysis pre-test probability increased from 25.9% to 65.4% after the use of the proposed model. This tool aims to assist the physician in deciding when to perform molecular studies for the diagnosis of α-thalassemia. The model is useful in places with few financial health resources.

Caracterización clínica y epidemiológica de población pediátrica costarricense con alfa-talasemia

Objetivo: Describir las características clínicas y epidemiológicas de pacientes con alfatalasemia atendidos en un hospital nacional pediátrico. Métodos: Estudio observacional descriptivo de corte transversal. Se estudia a 60 pacientes del Servicio de Hematología del Hospital Nacional de Niños "Dr. Carlos Sáenz Herrera", Caja Costarricense de Seguro Social, del 1° de enero de 2018 al 31 de enero de 2019, cuyas edades están comprendidas entre los 0 meses y 12 años 11 meses de edad, con índices hematimétricos sugestivos de alfa-talasemia y con electroforesis de hemoglobina patrón AA con HbA2 normal o disminuida. Análisis molecular: identificación de 21 mutaciones y deleciones más frecuentes para el gen de alfa-globina: 3.7, 4.2, 20.5, MED, FIL, SEA, THAI, anti-3.7 triplicación, HbConstant Spring, HbQuonSze, Hb Adana, HbKoya Dora, HbIcara, HbPakse, a2 poli A-1/2, a2-cd142, a1-cd14, a2-init-cd, a2-cd19, a2-IVS1, a2-cd59. Se utiliza el método de amplificación por reacción en cadena de la polimerasa e hibridación inversa del ácido desoxirribonucleico genómico en leucocitos de sangre periférica de los pacientes. Resultados: Se confirma la enfermedad en 44/60 casos (73%). La edad media al diagnóstico para estos casos es de 4.9 años (desviación estándar 3.0), predominó el sexo femenino en 52.3% de los casos. La provincia de Guanacaste reportó la mayor prevalencia de la enfermedad. El defecto genético delecional -3.7 Kb es el genotipo más frecuente. El fenotipo en el 77.2% de los casos indicó portador silente de alfa-talasemia. El 84.1% de los sujetos positivos para alfa-talasemia correlacionó con hipocromía, microcitosis y eritrocitosis en el hemograma inicial. El 9% de los casos evidenció la coexistencia de alfa-talasemia y anemia por deficiencia de hierro. Conclusiones: Este estudio demuestra que los hallazgos de índices eritrocitarios que indiquen hipocromía y microcitosis con aumento del cómputo de eritrocitos, índices férricos normales y una electroforesis de hemoglobina con patrón normal (AA) sugieren ser estudiados molecularmente por alfa-talasemia. La electroforesis de hemoglobina reportada como normal no excluye la condición de alfa-talasemia y debe realizarse el estudio molecular.

Objective: Describe the clinical and epidemiological characteristics of patients with alpha thalassemia in the Hematology Service of a national pediatric hospital. Methods: Cross-sectional descriptive observational study. 60 patients from the Hematology Service of the National Children's Hospital "Dr. Carlos Sáenz Herrera", Costa Rican Social Security Fund, from January 1, 2018 to January 31, 2019, with hematometric indices suggestive of alphaThalassemia, with AA standard hemoglobin electrophoresis with normal or decreased HbA2 with ages between 0 months and 12 years 11 months old. Molecular analysis: Identification of 21 mutations and deletions that includes the detection of the most frequent deletions/mutations for the alpha globin gene: 3.7, 4.2, 20.5, MED, FIL, SEA, THAI, anti-3.7 tripling, HbConstant Spring, HbQuonSze, Hb Adana, HbKoya Dora, HbIcara, HbPakse, a2 poli A-1/2, a2-cd142, a1-cd14, a2-init-cd, a2-cd19, a2-IVS1, a2-cd59. The reverse hybridization PCR amplification method of genomic DNA in peripheral blood leukocytes of patients isused. Results: Of the 60 cases studied, in 44/60 (73%) cases the disease is confirmed. The average age at diagnosis for these cases is 4.9 years (SD 3.0), the female sex predominated in 52.3% of the cases. Guanacaste reported the highest prevalence of the disease. The deletional genetic defect -3.7 Kb was the most frequent genotype and the phenotype in 77.2% of the cases was he silent carrier of alpha thalassemia. In 84.1% of subjects positive for alpha thalassemia, it correlated with hypochromia, microcytosis, and erythrocytosis in the initial blood count. 9% of the cases showed the coexistence of alpha thalassemia and iron deficiency anemia. Conclusions: This study demonstrates that the findings of erythrocyte indices that indicate hypochromia and microcytosis with increased erythrocyte count; normal iron indices and a normal hemoglobin (AA) electrophoresis pattern suggest that they should be studied molecularly for alpha thalassemia. Hemoglobin electrophoresis reported as normal does not exclude the condition of alpha thalassemia and the molecular study must be carried out.

The state of the art of fetal hemoglobin-inducing agents.

INTRODUCTION: Sickle cell anemia (SCA) is a hematological genetic disorder caused by a mutation in the gene of the ß-globin. Pharmacological treatments will continue to be an important approach, including the strategy to induce fetal hemoglobin (HbF). AREAS COVERED: Here, we analyzed the articles described in the literature regarding the drug discovery of HbF inducers. The main approaches for such strategy will be discussed, highlighting those most promising. EXPERT OPINION: The comprehension of the mechanisms involved in the ß-globin regulation is the main key to design new drugs to induce HbF. Among the strategies, gamma-globin regulation by epigenetic enzymes seems to be a promising approach to be pursued, although the comprehension of the selectivity role for those new drugs is crucial to reduce adverse effects. The low druggability of transcription factors and their vital role in embryonic human development are critical points that should be taken in account for drug design. The guanylate cyclase and the NO/cGMP signaling pathway seem to be promising not only for HbF induction, but also for the protective effects in the cardiovascular system. The association of drugs acting through different mechanisms to induce HbF seems to be promising for the discovery of new drugs.