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1.
Ann Hematol ; 99(9): 2019-2026, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32676731

RESUMO

Hyperbilirubinemia and pigment gallstones are frequent complications in transfusion-dependent ß-thalassemia (TDßT) patients. Bilirubin production and clearance are determined by genetic as well as environmental variables like ineffective erythropoiesis, hemolysis, infection-induced hepatic injury, and drug- or iron-related toxicities. We studied the frequency of the Gilbert syndrome (GS), a common hereditary cause of hyperbilirubinemia in 102 TDßT patients aged 13-43 years (median 26 years). Total and unconjugated hyperbilirubinemia were frequent (81.4% and 84.3% patients respectively). Twenty (19.6%) patients showed total bilirubin > 3.0 mg/dL; 53 (51.9%) had an elevation of either alanine or aspartate aminotransferase, or alkaline phosphatase liver enzymes. Nineteen (18.6% of the 92 tested) were positive for hepatitis B or C, or HIV. The mean total and unconjugated bilirubin levels and AST, ALT, and ALP levels in patients positive for hepatitis B or C were not significantly different from negative cases. Eighteen patients (17.7%) had GS: homozygous (TA)7/7 UGT1A1 promoter motif (the *28/*28 genotype), 48 (47.1%) were heterozygous (TA)6/7. Total + unconjugated bilirubin rose significantly with the (TA)7 allele dose. Fourteen (13.7%) patients had gallstones. There was no significant difference in total/unconjugated bilirubin in patients with/without gallstones and no significant differences in frequencies of gallstones within the three UGT1A1 genotypes. This largest study in Indian TDßT patients suggests that GS should be excluded in TDßT cases where jaundice remains unexplained after treatable causes like infections, chelator toxicity, or transfusion-related hemolysis are excluded. GS was not associated with gallstones, possibly due to a lower incidence of cholelithiasis overall, a younger age cohort, or other environmental factors.


Assuntos
Grupo com Ancestrais do Continente Asiático , Colelitíase/epidemiologia , Doença de Gilbert/epidemiologia , Glucuronosiltransferase , Hiperbilirrubinemia/epidemiologia , Talassemia beta/epidemiologia , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Transfusão de Sangue/tendências , Colelitíase/genética , Feminino , Doença de Gilbert/genética , Glucuronosiltransferase/genética , Humanos , Hiperbilirrubinemia/genética , Índia/epidemiologia , Masculino , Estudos Prospectivos , Adulto Jovem , Talassemia beta/genética , Talassemia beta/terapia
2.
Ann Hematol ; 99(7): 1475-1483, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32524201

RESUMO

Large deletions in the ß-globin gene cluster lead to increased HbF levels by delaying the γ- to ß-globin switch process. However, these deletions when inherited as a homozygous condition or when co-inherited with ß-thalassemia result in variable clinical phenotypes. Individuals or families with a clinically presenting child, where the parents had HbF levels ≥ 10%, were further screened for the presence of large ß-globin cluster deletions. Six deletions in the ß-globin gene cluster were screened by GAP-PCR, and the uncharacterized deletions were further analyzed by gene dosage or by multiplex ligation-dependent probe amplification (MLPA). Among 192 individuals suspected for the inheritance of large deletions, 138 were heterozygous for large deletions, 45 were compound heterozygous of a large ß-globin cluster deletion and ß-thalassemia, and 9 were found to be homozygous for deletions. Among the heterozygotes, the Asian Indian inversion-deletion was found to be the most common deletion (39.9%), followed by the HPFH-3 deletion (30.0%). Other deletions 49.3 kb, δß-thalassemia (21.2%), and 32.6 kb deletion (4.4%) were also found to be prevalent in our population. Patients compound heterozygous or homozygous for HPFH-3 and 32.6 kb deletions showed a milder clinical presentation, as compared with the patients compound heterozygous or homozygous for the Asian Indian inversion-deletion and 49.3 kb δß-thalassemia. This comprehensive study highlights the mutation spectrum of large ß-globin cluster deletions and the clinical heterogeneity in the patients homozygous or compound heterozygous with ß-thalassemia, thus asserting the need for molecular characterization of these deletions.


Assuntos
Hemoglobina Fetal/genética , Estudos de Associação Genética , Heterogeneidade Genética , Talassemia beta/epidemiologia , Talassemia beta/genética , Talassemia delta/epidemiologia , Talassemia delta/genética , Idade de Início , Criança , Mortalidade da Criança , Pré-Escolar , Feminino , Hemoglobina Fetal/análise , Estudos de Associação Genética/estatística & dados numéricos , Humanos , Índia/epidemiologia , Lactente , Padrões de Herança/genética , Masculino , Talassemia beta/sangue , Talassemia beta/mortalidade , Talassemia delta/sangue , Talassemia delta/mortalidade
3.
Infez Med ; 28(suppl 1): 89-95, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32532944

RESUMO

INTRODUCTION: Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat. Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported. PURPOSE: In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease. METHODS: Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed. RESULTS: We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection. Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection. CONCLUSION: More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity.


Assuntos
Infecções por Coronavirus/sangue , Pneumonia Viral/sangue , Adulto , Idoso , Biomarcadores , Proteína C-Reativa/análise , Doenças Cardiovasculares/epidemiologia , Comorbidade , Infecções por Coronavirus/epidemiologia , Feminino , Ferritinas/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Grécia/epidemiologia , Humanos , L-Lactato Desidrogenase/sangue , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Talassemia beta/epidemiologia
5.
Ann Hematol ; 99(9): 2037-2046, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32436014

RESUMO

Cardiovascular complications account for a substantial increase in morbidity and mortality in beta-thalassemia patients. Many patients have structural heart disease, and some of them present with symptomatic heart failure (HF). Quality of life (QOL) of beta-thalassemia patients is lower than that of the general population. The aim of our study was to explore the relationship between HF stages and QOL in beta-thalassemia patients. Seventy-three consecutive adult beta-thalassemia patients took part in this cross-sectional study. Stages of HF, classified with increasing severity as A, B, and C, were determined based on ACC/AHA guidelines. QOL was assessed using the SF-36 questionnaire. Fifteen patients had stage C HF, twenty-eight had stage B HF, and the remaining were considered stage A patients, as beta thalassemia is a predisposing factor for HF. All QOL domains except for bodily pain were significantly lower in stage C patients than in stage A patients. Stage C patients had significantly lower QOL scores for physical functioning, role physical, and social functioning domains than stage B patients. Stage B patients' QOL differed from stage A patients only in the vitality domain. In the multiple regression analysis which took several demographic and clinical factors into account, stage of HF was the most important factor associated with QOL, and negatively and significantly related to five QOL domains, namely physical functioning, role physical, general health, social functioning, and vitality. In conclusion, QOL is negatively affected by the severity of heart failure in beta-thalassemia patients.


Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Talassemia beta/epidemiologia , Talassemia beta/psicologia , Adulto , Estudos Transversais , Feminino , Grécia/epidemiologia , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Talassemia beta/diagnóstico
6.
Med Hypotheses ; 142: 109827, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32447232

RESUMO

The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent PRE-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta-chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research.


Assuntos
Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Talassemia beta/imunologia , Betacoronavirus , Infecções por Coronavirus/complicações , Feminino , Hemoglobinas/análise , Hemoglobinas/química , Heterozigoto , Humanos , Sistema Imunitário , Imunização , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Prevalência , Análise de Regressão , Resultado do Tratamento , Talassemia beta/complicações , Talassemia beta/epidemiologia
9.
Gene ; 741: 144544, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32165295

RESUMO

The Maldives is an archipelago of 407,660 people according to population census of 2014, made up of 20 atolls, which has one of the highest prevalence of ß-thalassemia worldwide. However, there is a dearth of studies related to ß-thalassemia in the Maldives; therefore, in this study, we aimed to investigate the genetic epidemiology of ß-thalassemia in Maldives. Blood samples were collected from 110,504 participants (1992-2015). Hemoglobin and RBC indices were measured on automated hematology analyzers. The quantitation of hemoglobin, HbA2, Hb F, and other abnormal Hb variants were assessed by HPLC. Molecular analysis was performed for the most common mutations in Southeast Asia for only 874 individuals either heterozygous or homozygous for these mutations using reverse dot blot hybridization. We screened 110,504 individuals for ß-thalassemia between 1992 and 2015, which is ~ 30% of the entire population. The ß-thalassemia carrier frequency was estimated to be 16.2%. Molecular diagnosis of 874 ß-thalassemia carriers/major was performed for the most common seven mutations in Southeast Asia; of these, 139 patients were diagnosed as ß-thalassemia major. This analysis showed that the most common mutations were IVS1 + 5G > C, (678; 77.6%), followed by the CD 30 (136; 15.6%). The least frequent mutation was FS8/9, (1, 0.001%), followed by IVS1 + 1G > T and CD15 (2; 0.2%). The frequency of ß-thalassemia varies significantly among the 20 different atolls in Maldives. This study is expected to improve genetic counseling, creating awareness, enhance premarital screening, and customize the prevention and treatment strategies based on the needs of each atoll.


Assuntos
Aconselhamento Genético , Epidemiologia Molecular , Globinas beta/genética , Talassemia beta/genética , Feminino , Genótipo , Hemoglobinas Anormais/genética , Heterozigoto , Humanos , Ilhas do Oceano Índico , Masculino , Programas de Rastreamento/métodos , Mutação , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
10.
BMC Med Genet ; 21(1): 43, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32111191

RESUMO

BACKGROUND: Individuals with δß-thalassemia/HPFH and ß-thalassemia usually present with intermedia or thalassemia major. No large-scale survey on HPFH/δß-thalassemia in southern China has been reported to date. The purpose of this study was to examine the molecular epidemiology and hematologic characteristics of these disorders in Guangzhou, the largest city in Southern China, to offer advice for thalassemia screening programs and genetic counseling. METHODS: A total of 125,661 couples participated in pregestational thalassemia screening. 654 subjects with fetal hemoglobin (HbF) level ≥ 5% were selected for further investigation. Gap-PCR combined with Multiplex ligation dependent probe amplification (MLPA) was used to screen for ß-globin gene cluster deletions. Gene sequencing for the promoter region of HBG1 /HBG2 gene was performed for all those subjects. RESULTS: A total of 654 individuals had hemoglobin (HbF) levels≥5, and 0.12% of the couples were found to be heterozygous for HPFH/δß-thalassemia, including Chinese Gγ (Aγδß)0-thal, Southeast Asia HPFH (SEA-HPFH), Taiwanese deletion and Hb Lepore-Boston-Washington. The highest prevalence was observed in the Huadu district and the lowest in the Nansha district. Three cases were identified as carrying ß-globin gene cluster deletions, which had not been previously reported. Two at-risk couples (0.0015%) were required to receive prenatal diagnosis. We also found 55cases of nondeletional-HPFH (nd-HPFH), including 54 with Italian nd-HPFH and one with the Aγ-197C-T heterozygous state. It is difficult to discriminate between Chinese Gγ (Aγδß)0-thal and Italian nd-HPFH carriers using hemoglobin (Hb) analysis. CONCLUSIONS: This study is the first to describe the familial prevalence of HPFH/δß-thalassemia and the high-risk rate in Greater Guangzhou Area, and the findings will support the implementation of thalassemia screening for three common deletions by gap-PCR. We also presented a systematic description of genotype-phenotype relationships which will be useful for genetic counseling and prenatal diagnostic services for ß-thalassemia intermedia.


Assuntos
Hemoglobina Fetal/genética , Talassemia beta/epidemiologia , Talassemia beta/genética , Talassemia delta/epidemiologia , Talassemia delta/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , China/epidemiologia , Cidades/epidemiologia , Família , Feminino , Hemoglobinas Anormais/genética , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Prevalência , Adulto Jovem , Globinas beta/genética , Talassemia beta/sangue , Talassemia delta/sangue
11.
BMC Med Genet ; 21(1): 6, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31906886

RESUMO

BACKGROUND: Thalassemia is a group of inherited hemoglobic disorders resulting from defects in the synthesis of one or more of the hemoglobin chains, which is one of the most prevalent inherited disorders in southern China. Only few studies reported the molecular characterization of α- and ß-Thalassemia in Hubei Province in the central of China. METHODS: A total of 4889 clinically suspected cases of thalassemia were analyzed by Gap-PCR, PCR-based reverse dot blot (RDB). RESULTS: 1706 (33.8%) subjects harbored thalassemia mutations, including 539 (11.0%) subjects with α-thalassemia, 1140 (23.3%) subjects with ß-thalassemia mutations, and 25 (0.51%) subjects with both α- and ß-thalassemia mutations. Seven genotypes of α-thalassemia mutations and 29 genotypes of ß-thalassemia mutations were characterized. --SEA/αα (66.05%), -α3.7/αα (24.12%), and -α4.2/αα (3.71%) accounted for 93.88% of the α-thalassemia mutations. ßIVS-II-654/ßN, ßCD41-42/ßN, ßCD17/ßN, ßCD27-28/ßN, ßCD71-72/ßN, ß - 28/ßN, ß - 29/ßN, ßCD43/ßN, ßE/ßN, accounting for 96.40% of all ß-thalassemia genotypes. Furthermore, mean corpuscular volume (MCV) and mean corpuscular Hb (MCH) were sensitive markers for both ß-thalassemia and α-thalassemia with --SEA/αα, but not -α3.7/αα and -α4.2/αα. CONCLUSIONS: Our data indicated great heterogeneity and extensive spectrum of thalassemias in Hubei province of China.


Assuntos
Genética Populacional , Hemoglobinas/genética , Talassemia alfa/genética , Talassemia beta/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , China , Feminino , Heterogeneidade Genética , Genótipo , Hemoglobinas/biossíntese , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem , Talassemia alfa/epidemiologia , Talassemia beta/sangue , Talassemia beta/epidemiologia
12.
J Clin Pathol ; 73(5): 278-282, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31653757

RESUMO

AIMS: Thalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and ß-thalassemia in the Quanzhou region of Fujian province, a city with high incidence of thalassemia in Southeast China. METHODS: A total of 11 668 cases were collected in Quanzhou region from January 2013 to June 2019. The deletions of α-thalassemia were detected by Gap-PCR, α-thalassemia and ß-thalassemia mutations were detected by DNA reverse dot blot hybridisation. Rare thalassemia gene testing and DNA sequencing were performed to detect rare and novel thalassemia mutation for suspected rare thalassemia carriers. RESULTS: Among 11 668 subjects, 4796 (41.10%) subjects were diagnosed with thalassemia. 3298 (28.27%) subjects were α-thalassemia carriers, 26 types of α-thalassemia mutations were identified, with the common α-thalassemia genotypes being --SEA/αα (71.47%), -α3.7/αα (17.13%) and -α4.2/αα (3.49%). 1407 (12.06%) subjects were ß-thalassemia carriers, 18 types of ß-thalassemia mutations were identified. The common five genotypes of ß-thalassemia were ßIVS-II-654/ßN (36.53%), ßCD41-42/ßN (30.28%), ßCD17/ßN (17.13%), ßCD26/ßN (5.12%) and ß-28/ßN (4.62%). Additionally, 91 (0.78%) subjects with composite α-thalassemia and ß-thalassemia were identified. Furthermore, 9 α-thalassemia and ß-thalassemia gene mutations (CAP +40-43 (-AAAC), IVS-I-1 (G>T), IVS-I-5 (G>C), SEA-HPFH, CD53 (-T), CD37 (A>G), -90 (C>T), CD3 (T>C), -α6.9) were identified for the first time in the region. Among them, CD53 (-T), CD37 (A>G) and -90 (C>T) mutations were identified for the first time in Fujian province. Moreover, CD3 (T>C), -α6.9 mutations were first identified in Chinese individual. CONCLUSIONS: Quanzhou region of South China has high incidence of thalassemia mutations. In this study, several cases of rare thalassemia mutations have been identified, providing reference for clinical consultation. The completion of this study is of great significance to strengthen the prevention and control of thalassaemia in the Quanzhou region.


Assuntos
Mutação , Talassemia alfa/genética , Talassemia beta/genética , Adolescente , Adulto , China , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sequência de DNA , Adulto Jovem , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
13.
PLoS One ; 14(12): e0216020, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830127

RESUMO

BACKGROUND: The diagnosis of sickle cell disease (SCD) is made by hemoglobin assays such as high-performance liquid chromatography (HPLC), isoelectric focusing and cellulose acetate or citrate agar electrophoresis. These assays are easy to perform and used in large-scale newborn screening in many countries. These tests however may not easily differentiate Sß0 thalassemia from SS or identify other hemoglobin variants, and in this case, hemoglobin (HBB) gene sequencing may be necessary. OBJECTIVES: To develop a high throughput DNA based confirmatory assay for SCD and to detect mutations in the HBB gene. METHODS: We developed an automated pyrosequencing technique (PyS) based on QIAGEN technology (Hilden, Germany) to detect homozygous or heterozygous hemoglobin S mutations as well as hemoglobin C mutations. The technique was tested on 2,748 samples from patients enrolled in a multi-center SCD cohort in Brazil. Patients were previously tested using HPLC to diagnose SCD as part of routine clinical care. Any subjects with discrepant results between HPLC and PyS or with heterozygous hemoglobin S detected had Sanger sequencing of the HBB gene. RESULTS: We identified 168 samples with discrepant results between HPLC and PyS and 100 with concordant PyS = heterozygous S and HPLC, which would suggest SB-thalassemia or other heterozygous S variants. The PyS assay correctly identified 1906 (98.7%) of the 1930 HbSS and 628 (98.7%) of the 636 HbSC samples. Of the 179 remaining samples, PyS correctly indicated S heterozygosis in 165 (92.2%). Of the 165 heterozygous S samples confirmed by Sanger as consistent with Sß thalassemia genotype, 84 samples were classified as Sß0 thalassemia and 81 as Sß+ thalassemia. The most frequent beta thalassemia mutations of Sß0 and Sß+ were HBB: c.118C>T (Gln40Stop) and HBB c.92 + 6T> C, respectively. DISCUSSION: The PyS proved to be satisfactory for large-scale confirmatory testing of hemoglobin mutation. Moreover, with this study we were able to describe the most common ß+ and ß0 mutations in SCD patients with Sß-thalassemia in a large multi-institutional SCD cohort in Brazil.


Assuntos
Anemia Falciforme/diagnóstico , Hemoglobina Falciforme/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Talassemia beta/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Brasil/epidemiologia , Estudos de Coortes , Genótipo , Humanos , Talassemia beta/epidemiologia , Talassemia beta/genética
14.
Indian J Med Res ; 150(2): 161-166, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31670271

RESUMO

Background & objectives: Swiss-type hereditary persistence of foetal haemoglobin (HPFH) has been shown to be responsible for the wide range of F cell levels in healthy Thai adults. However, a survey for F cells in healthy Thai adults has not been performed. This study was conducted to determine the F cell distribution in adult Thai blood donors and to assess the possible involvement of ß-thalassaemia and haemoglobin E (HbE) carriers in increased HbF levels. Methods: Thai blood donors (n=375, 205 males and 170 females) were included in the study. Blood samples were collected for measuring haemoglobin (Hb) concentration and haematocrit (Hct) and F cell levels. Hb and Hct levels were determined by automated blood counter, while F cells were quantified by flow cytometric analysis of F cells stained by fluorescein isothiocyanate-conjugated anti γ-globin monoclonal antibody. Finally, F cell levels were compared between blood samples having mean corpuscular volume (MCV ) <80 fl and ≥80 fl as well as between ß-haemoglobinopathies (HbE and ß-thalassaemia carriers) and normal adults. Results: F cell levels varied markedly spanning 0.80-39.2 per cent with a positively skewed distribution. Thirty two per cent of these individuals had F cell levels more than the 4.5 per cent cut-off point. F cell levels in females were significantly higher than those in males (P<0.05). F cell levels in individuals having MCV <80 fl were significantly higher than those having MCV ≥80 fl (P<0.05). ß-haemoglobinopathy (HbE and ß-thalassaemia carriers) had significantly higher F cell levels than normal individuals (P<0.05). Interpretation & conclusions: The present results showed that besides Swiss-type HPFH, the ß-haemoglobinopathy was expected to be involved in increased F cell levels in adult Thais. Thus, influence of ß-haemoglobinopathy must be considered in interpreting F cell levels in area endemic of this globin disorder.


Assuntos
Hemoglobina Fetal/genética , Hemoglobina E/genética , Hemoglobinopatias/genética , Talassemia beta/genética , Adulto , Anemia Falciforme/sangue , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Anemia Falciforme/patologia , Doadores de Sangue , Pré-Escolar , Índices de Eritrócitos/genética , Feminino , Hemoglobinopatias/sangue , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/patologia , Heterozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Tailândia , Talassemia beta/sangue , Talassemia beta/epidemiologia , Talassemia beta/patologia
15.
Croat Med J ; 60(5): 405-413, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31686454

RESUMO

AIM: To determine whether serum ferritin, liver transaminases, and regularity and type of iron chelation protocol can be used to predict liver iron load as assessed by T2* magnetic resonance imaging (MRI) in patients with beta thalassemia major (TM). METHODS: This cross-sectional study, conducted from March 1, 2014 to March 1, 2015, involved 90 patients with beta TM on regular packed red blood cell transfusion. Liver and cardiac iron load were evaluated with T2* MRI. Compliance with iron-chelating agents, deferoxamine or deferasirox, and regularity of their use, as well as serum ferritin and liver transaminase levels were assessed. RESULTS: Patients with high serum ferritin were 2.068 times (95% confidence interval 1.26-3.37) more likely to have higher liver or cardiac iron load. High serum aspartate aminotransferases and irregular use of iron chelating agents, but not their type, predicted higher cardiac iron load. In a multiple regression model, serum ferritin level was the only significant predictor of liver and myocardial iron load. CONCLUSIONS: Higher serum ferritin strongly predicted the severity of cardiac and liver iron load. Irregular use of chelator drugs was associated with a higher risk of cardiac and liver iron load, regardless of the type of chelating agent.


Assuntos
Ferritinas/sangue , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro , Talassemia beta , Estudos Transversais , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/terapia , Fígado/química , Fígado/diagnóstico por imagem , Imagem por Ressonância Magnética , Adesão à Medicação/estatística & dados numéricos , Talassemia beta/sangue , Talassemia beta/complicações , Talassemia beta/epidemiologia , Talassemia beta/terapia
16.
Hemoglobin ; 43(4-5): 223-228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31603010

RESUMO

ß-Thalassemia (ß-thal) is a genetic disorder representing a major health problem in Algeria. Our first objective was to determine the allelic frequencies and molecular spectrum of ß-thal mutations in patients with major hemoglobinopathies [ß-thal major (ß-TM) and sickle cell disease] in three provinces of northeast Algeria. Our second objective was to assess if the clinical management of ß-TM patients depended on their region of origin. Our last objective was to assess a population originating from Maghreb, the reliability of the thalassemia severity score (TSS) for patients with homozygous ß-thal. Sanger HBB gene sequencing was performed on 59 patients with sickle cell disease and 60 with ß-TM. For the latter patients, the genetic modifiers of the TSS were genotyped: α-thalassemia (α-thal) deletions and four Hb F-inducing polymorphisms (XmnI, rs1427407 and rs10189857 for BCL11A and rs9399137 for HMIP). Eleven different ß-thal mutations were found but two of them (HBB: c.118C>T and HBB: c.93-21G>A) accounted for about 70.0% of the ß-thal alleles. A relatively high proportion of Hb S (HBB: c.20A>T)/ß-thal genotypes (27.0%) was found in our sickle cell disease cohort where a new frameshift ß0-thal mutation (HBB: c.374dup; p.Pro126Thrfs*15) was identified. No difference was found in the three provinces. Of the 60 ß-TM patients, those with a high or very high TSS were significantly younger at the age of first transfusion, thus assessing the reliability of this scoring system in a Maghrebin cohort. Trends for a lower age of splenectomy and high ferritin levels were also detected for the higher TSS categories.


Assuntos
Índice de Gravidade de Doença , Talassemia beta/genética , Adulto , Argélia/epidemiologia , Anemia Falciforme/genética , Transfusão de Sangue , Feminino , Ferritinas/sangue , Mutação da Fase de Leitura , Genótipo , Hemoglobina Falciforme/genética , Hemoglobinopatias/genética , Humanos , Masculino , Esplenectomia , Talassemia beta/epidemiologia
17.
Rev Bras Epidemiol ; 22Suppl 02(Suppl 02): E190007.SUPL.2, 2019.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31596378

RESUMO

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.


Assuntos
Inquéritos Epidemiológicos/métodos , Traço Falciforme/epidemiologia , Talassemia beta/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Brasil/epidemiologia , Cromatografia Líquida de Alta Pressão , Estudos Transversais , Feminino , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Distribuição por Sexo , Fatores Socioeconômicos , Adulto Jovem
18.
Saudi Med J ; 40(9): 887-892, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31522215

RESUMO

OBJECTIVES: To evaluate any association between the frequency of hereditary hemochromatosis (HFE) gene mutation (H63D and C282Y) and iron overload in beta-thalassemia major (BTM) patients. METHODS: The case-control study was conducted from June 2016 to February 2018. Blood samples from 204 BTM patients and 204 normal controls were taken from the Sundas Foundation Blood Bank. These samples were analyzed for serum ferritin assay and HFE mutation. Ferritin level was measured on the ARCHITECT 1000SR. Both patient and control samples were analyzed for mutations using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Serum ferritin levels for all patients were greater than 1000ng/mL. The p.H63D mutation was observed in 23 (11.3%) cases, out of which 19 cases were heterozygous for p.H63D and 4 cases were homozygous. In control samples, 4 cases (2%) were found heterozygous for the p.H63D, and no homozygous mutation was found. Significantly high serum ferritin levels were found in BTM patients with the H63D mutation (p=0.00). In the case of p.C282Y, neither homozygous nor heterozygous mutation was found in patients or in controls. CONCLUSION: H63D polymorphism is associated with iron overload in BTM patients. Larger-scale research is required to give an elaborated view of the association of the HFE mutation with iron overload in these patients and to confirm our conclusion.


Assuntos
Ferritinas/sangue , Proteína da Hemocromatose/genética , Hemocromatose/sangue , Talassemia beta/sangue , Adulto , Transfusão de Sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Comorbidade , Feminino , Hemocromatose/epidemiologia , Hemocromatose/genética , Humanos , Sobrecarga de Ferro/sangue , Sobrecarga de Ferro/epidemiologia , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/genética , Masculino , Mutação , Paquistão/epidemiologia , Prevalência , Reação Transfusional , Talassemia beta/epidemiologia , Talassemia beta/genética
19.
Blood Rev ; 38: 100594, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31416718

RESUMO

Thalassemia is among the most common monogenic diseases worldwide. Stem cell transplantation can be curative but is reserved for young patients, as probably gene therapy will be in the future. Adult thalassemia patients are treated with transfusion therapy and iron chelation, and improvements in the safety of transfusion protocols, use of iron chelation, monitoring of iron overload, and management of comorbidities have substantially prolonged survival, increasing the proportion of adult patients in the thalassemic population. However, older patients are more likely to develop multiple disease-related morbidities, including osteoporosis, endocrine disorders, liver disease, renal dysfunction, and cancer. Thus, the main objective of this article is to describe new challenges posed by the increasing life expectancy of patients with thalassemia, focusing on data from Italy where there is a well-documented history of thalassemia management. It is hoped that the mortality and morbidity benefits already seen in patients with thalassemia will continue to improve with ongoing advances in the quality of treatment.


Assuntos
Transfusão de Sangue , Quelantes de Ferro/uso terapêutico , Talassemia beta/terapia , Transfusão de Sangue/métodos , Gerenciamento Clínico , Humanos , Itália/epidemiologia , Talassemia beta/complicações , Talassemia beta/epidemiologia
20.
PLoS One ; 14(8): e0220852, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31419232

RESUMO

OBJECTIVES: Our aim was to describe the numbers and distribution of patients with different types of thalassemia and to assess the standards of care in all thalassemia treatment centers throughout Sri Lanka and the success of the ongoing prevention programme. METHODS: This cross-sectional island-wide survey was conducted by two trained medical graduates, who visited each thalassemia center to collect data from every patient, using a standardized form. Data was collected through review of patient registers and clinical records. RESULTS: We collected data on 1774 patients from 23 centers. 1219 patients (68.7%) had homozygous ß-thalassemia, 360 patients (20.3%) had hemoglobin E ß-thalassemia, and 50 patients (2%) had sickle ß-thalassemia. There were unacceptably high serum ferritin levels in almost all centers. The annual number of births of patients with ß-thalassaemia varied between 45-55, with little evidence of reduction over 19 years. CONCLUSIONS: Central coordination of the treatment and ultimately prevention of thalassemia is urgently needed in Sri Lanka. Development of expert centers with designated staff with sufficient resources will improve the quality of care and is preferred to managing patients in multiple small units.


Assuntos
Talassemia/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde , Sri Lanka/epidemiologia , Talassemia/epidemiologia , Talassemia/terapia , Talassemia beta/epidemiologia , Talassemia beta/prevenção & controle , Talassemia beta/terapia
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