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1.
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
3.
Health Qual Life Outcomes ; 17(1): 137, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395066

RESUMO

BACKGROUND: Thalassaemia is a chronic disease without an effective cure in a majority. The clinical management has improved considerably during recent years; however, minimal attempts are made to up lift the quality of life among patients, especially in developing countries. Here we aim to describe and compare and to determine factors associated with health related quality of life among patients with transfusion dependent ß-thalassaemia major and haemoglobin E ß-thalassemia in Sri Lanka. METHODS: A case control study was conducted in the three largest thalassaemia centres of Sri Lanka. All patients with transfusion dependent ß-thalassaemia (ß-thalassaemia major and haemoglobin E ß-thalassaemia) aged 5-18 years were recruited as cases whilst a randomly selected group of children without chronic diseases were recruited as controls. Socio-demographic and clinical data were collected using an interviewer-administered questionnaire and health related quality of life was measured using the validated Paediatric Quality of Life Inventory Version 4.0. RESULTS: Two hundred and seventy one patients with transfusion dependent ß-thalassaemia (male-49.1%; mean age- 10.9 ± 3.6 years) and 254 controls (male-47.2%; mean age- 10.4 ± 3.5 years) were recruited. Mean health-related quality of life scores were significantly lower in patients compared to controls (72.9 vs. 91.5, p < 0.001). Of the patients, 224 (84%) had ß-thalassaemia major and 43 (16%) had haemoglobin E ß-thalassaemia. Quality of life scores in psychological health (p < 0.05), emotional functioning (p < 0.05) and social functioning (p < 0.05) were significantly lower in patients with haemoglobin E ß-thalassaemia compared to ß-thalassaemia major. Splenectomy (p < 0.05), short stature (p < 0.05), under nutrition (p < 0.05) and longer hospital stays (p < 0.05) were significantly associated with lower quality of life scores. CONCLUSIONS: Despite improvements in management, the quality of life among patients with ß-thalassaemia still remains low. This is more pronounced in the subset of patients with haemoglobin E ß-thalassaemia. Splenectomy, short stature, undernutrition and longer hospital stays were significantly associated with poor quality of life. It is timely, even in developing countries, to direct emphasis and to take appropriate steps to improve standards of living and quality of life of patients with ß-thalassaemia.


Assuntos
Qualidade de Vida , Talassemia beta/psicologia , Adolescente , Estudos de Casos e Controles , Criança , Estudos de Coortes , Feminino , Hemoglobina E , Humanos , Masculino , Sri Lanka , Inquéritos e Questionários , Talassemia beta/classificação , Talassemia beta/terapia
4.
Blood Rev ; 37: 100588, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324412

RESUMO

Patients with ß-thalassemia major (BTM) require regular blood transfusions, supported by appropriate iron chelation therapy (ICT), throughout their life. ß-thalassemia is a global disease that is most highly prevalent in Southeast Asia, Africa, and Mediterranean countries. However, the global distribution of patients with ß-thalassemia is changing due to population migration, and Northern European countries now have significant thalassemia populations. Globally, many patients with BTM have limited access to regular and safe blood transfusions. A lack of voluntary nonremunerated blood donors, poor awareness of thalassemia, a lack of national blood policies, and fragmented blood services contribute to a significant gap between the timely supply of, and demand for, safe blood. In many centers, there is inadequate provision of antigen testing, even for common red cell antigens such as CcEe and Kell. Policies to raise awareness and increase the use of red blood cell antigen testing and requesting of compatible blood in transfusion centers are needed to reduce alloimmunization (the development of antibodies to red blood cell antigens), which limits the effectiveness of transfusions and the potential availability of blood. Patients with BTM are also at risk of transfusion-transmitted infections unless appropriate blood screening and safety practices are in place. Hence, many patients are not transfused or are undertransfused, resulting in decreased health and quality-of-life outcomes. Hemovigilance, leukoreduction, and the ability to thoroughly investigate transfusion reactions are often lacking, especially in resource-poor countries. ICT is essential to prevent cardiac failure and other complications due to iron accumulation. Despite the availability of potentially inexpensive oral ICT, a high proportion of patients suffer complications of iron overload and die each year due to a lack of, or inadequate, ICT. Increased awareness, training, and resources are required to improve and standardize adequate blood transfusion services and ICT among the worldwide population of patients with BTM. ICT needs to be available, affordable, and correctly prescribed. Effective, safe, and affordable new treatments that reduce the blood transfusion burden in patients with ß-thalassemia remain an unmet need.


Assuntos
Transfusão de Sangue/métodos , Talassemia beta/terapia , Humanos , Talassemia beta/patologia
5.
J Pak Med Assoc ; 69(7): 959-963, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31308562

RESUMO

OBJECTIVE: To find frequency ofalpha Thalsaemia nhomozygous beta Thalsaemia patients, and to se any difernce infrequency and age ofirst ransfusion and mean haemoglobin concentration. METHODS: The single-centred, escriptive cros-sectional study was conducted athe National Instiute of Blod Disease and Bone Marow Transplantaion, Karchi, from June 1,2012, to May 31, 2013. Patients of homozygous beta halsaemia, diagnosed by polymerase chain reaction, wer tested for coinheritance of alpha Thalsaemia nd foetal haemoglobin XMN1 polymorphism using polymerase chain reaction. SPS 17 was used for dat anlysi. RESULTS: Of the 286 patients, 19(41.6%) wer males, and 9(34.6%) showed coinheritance ofalpha thalsaemia. In the coinheritance group, 50(50%) and 1(1%) patients recived 1-20 and 21-40 times transfusions per year espectively, while inthe non-coinheritance group, the coresponding numbers wer 125(67%) and 27(14.%). Overal, 73(25.%) patients had nevr ben transfused, including 38(13.%) patients inthe alpha Thalsaemia group. XMN1 polymorphism was found in 86(41%) ofthe 208 patients who wer tested and anlysed on this count. CONCLUSIONS: Alpha thalsemia was presnt inmore than one-third homozygous beta halsemia patients.


Assuntos
Talassemia alfa/epidemiologia , Talassemia beta/epidemiologia , Adolescente , Transfusão de Sangue , Criança , Pré-Escolar , Comorbidade , Feminino , Homozigoto , Humanos , Lactente , Recém-Nascido , Masculino , Paquistão/epidemiologia , alfa-Globinas/genética , Talassemia alfa/sangue , Talassemia alfa/genética , Talassemia alfa/terapia , Globinas beta/genética , Talassemia beta/sangue , Talassemia beta/genética , Talassemia beta/terapia
6.
Cells ; 8(7)2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269695

RESUMO

Background: The aim of the study was to investigate the intra-host variability through next-generation-sequencing (NGS) of the NS5A-gene in nosocomial transmission-clusters observed in two Italian hospitals among hepatitis C virus (HCV)-genotype-1b infected patients. Methods: HCV-sequencing was performed by Sanger-sequencing (NS3 + NS5A + NS5B) and by NGS (NS5A, MiSeq-Illumina) in 15 HCV-1b infected patients [five acute with onco-hematologic-disease and 10 (4/6 acute/chronic) with ß-thalassemia]. Resistance-associated-substitutions (RAS) were analysed by Geno2pheno-algorithm. Nucleotide-sequence-variability (NSV, at 1%, 2%, 5%, 10% and 15% NGS-cutoffs) and Shannon entropy were estimated. Phylogenetic analysis was performed by Mega6-software and Bayesian-analysis. Results: Phylogenetic analysis showed five transmission-clusters: one involving four HCV-acute onco-hematologic-patients; one involving three HCV-chronic ß-thalassemia-patients and three involving both HCV-acute and chronic ß-thalassemia-patients. The NS5A-RAS Y93H was found in seven patients, distributed differently among chronic/acute patients involved in the same transmission-clusters, independently from the host-genetic IL-28-polymorphism. The intra-host NSV was higher in chronic-patients versus acute-patients, at all cutoffs analyzed (p < 0.05). Even though Shannon-entropy was higher in chronic-patients, significantly higher values were observed only in chronic ß-thalassemia-patients versus acute ß-thalassemia-patients (p = 0.01). Conclusions: In nosocomial HCV transmission-clusters, the intra-host HCV quasispecies divergence in patients with acute-infection was very low in comparison to that in chronic-infection. The NS5A-RAS Y93H was often transmitted and distributed differently within the same transmission-clusters, independently from the IL-28-polymorphism.


Assuntos
Infecção Hospitalar/virologia , Hepacivirus/genética , Hepatite C/virologia , Proteínas não Estruturais Virais/genética , Talassemia beta/terapia , Doença Aguda , Adulto , Substituição de Aminoácidos , Antivirais/farmacologia , Antivirais/uso terapêutico , Transfusão de Sangue , Doença Crônica , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/transmissão , Farmacorresistência Viral/genética , Feminino , Genótipo , Hepacivirus/patogenicidade , Hepatite C/tratamento farmacológico , Hepatite C/transmissão , Sequenciamento de Nucleotídeos em Larga Escala , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Interferons/genética , Interferons/imunologia , Masculino , Pessoa de Meia-Idade , Filogenia , Polimorfismo de Nucleotídeo Único , Talassemia beta/genética , Talassemia beta/imunologia
7.
J Coll Physicians Surg Pak ; 29(7): 635-638, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31253214

RESUMO

OBJECTIVE: To determine the effectiveness of Mahidol Scoring for assessing various grades of ß thalassemia intermedia. STUDY DESIGN: Cross-sectional study. PLACE AND DURATION OF STUDY: Fatima Memorial Hospital, Shadman, Lahore, from August 2016 to August 2017. METHODOLOGY: A total of 150 patients, both inpatient and outpatient diagnosed as thalassaemia intermedia fulfilling inclusion criteria, were enrolled, interviewed and examined after an informed consent. All patients were assessed by using Mahidol Scoring system. Their scores were documented on a predesigned evaluation porforma. Patients were labelled as mild, moderate or severe diseased. RESULTS: In a total of 150 patients, 88 (58.7%) were males and 62 (41.3%) were females. Using Mahidol Scoring, 88 (58.7%) were labelled as mild, 53 (35.3%) as moderate and 9 (6%) as severe diseased. Patient who were labelled as mild diseased according to Mahidol Scoring, had no blood transfusions and showed good response to hydroxyurea. Patients with moderate score, were infrequently transfused and showed variable response to hydroxyurea. Patients in severe group received first transfusion at an early age, maintained lower Hb levels, showed growth retardation, splenomegaly, and had poor response to hydroxyurea. CONCLUSION: Mahidol Scoring system is an easy, safe and effective way for classification of thalassaemia Intermedia severity. The grades according to Mahidol Scoring system will aid in the management of patients as the score can be quickly calculated, and can assist the clinician in an initial evaluation for disease severity in patients of thalassaemia intermedia.


Assuntos
Talassemia beta/diagnóstico , Antidrepanocíticos/uso terapêutico , Transfusão de Sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Hidroxiureia/uso terapêutico , Masculino , Paquistão , Índice de Gravidade de Doença , Talassemia beta/complicações , Talassemia beta/terapia
8.
Ann Hematol ; 98(8): 1827-1834, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31190133

RESUMO

In this study, we aimed to investigate the pattern and association of genetic mutations occurring within the alpha hemoglobin-stabilizing protein (AHSP) gene among HbE beta thalassemia patients with varying phenotypic expressions. Fifty-four diagnosed cases of HbE beta thalassemia (transfusion dependent and independent) were included in the study. Among them, 38 patients with similar genotypes (IVS 1-5, alpha gene deletion and triplication, Xmn polymorphism) were selected for further analysis. AHSP gene sequencing was done for these 38 samples to study associated mutations in AHSP gene. HbE beta thalassemia patients with similar genotypes but different phenotypic expressions were found to have mutations in the AHSP gene. There were five mutations found most prevalent among the samples analyzed for AHSP gene sequencing. Among these, two mutations were from intron 1 region of AHSP and three mutations were found in exon 3. The most prevalent mutation was found at the Oct binding site at intron 1 of AHSP. The mutations in exon 3 were more prevalent among the TDT groups. A mutation in exon 3 changing the amino acid (33rd) from serine to phenylalanine was found to be associated with only TDT group. This study documents that among the HbE beta thalassemia patients with varying severity, an exon mutation in AHSP is significantly prevalent only among the TDT group. Further understanding of the mechanism will shed light upon the impact of AHSP in modifying the disease severity in thalassemia.


Assuntos
Proteínas Sanguíneas/genética , Deleção de Genes , Duplicação Gênica , Hemoglobina E/genética , Chaperonas Moleculares/genética , Talassemia beta/genética , Adolescente , Adulto , Sequência de Bases , Proteínas Sanguíneas/metabolismo , Transfusão de Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Análise Mutacional de DNA , Eritrócitos/metabolismo , Eritrócitos/patologia , Éxons , Feminino , Expressão Gênica , Genótipo , Hemoglobina E/metabolismo , Humanos , Íntrons , Masculino , Pessoa de Meia-Idade , Modelos Moleculares , Chaperonas Moleculares/metabolismo , Fenótipo , Estrutura Secundária de Proteína , Índice de Gravidade de Doença , Talassemia beta/metabolismo , Talassemia beta/patologia , Talassemia beta/terapia
9.
Pediatr Emerg Care ; 35(7): e118-e120, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31219970

RESUMO

Yersinia enterocolitica infection, or yersiniosis, is a common cause of gastroenteritis in developing nations, but the disease is less common in the developed world. Yersiniosis typically presents as a self-limited gastroenteritis in an immunocompetent patient and rarely progresses to the more fulminant disseminated form. Certain patient populations are at greater risk of disseminated disease, and providers caring for these patients should have heightened suspicion for invasive disease. Patients dependent on serial transfusion therapy, such as those with inherited hemoglobinopathies, often have chronically elevated serum iron levels. These patients are at increased risk of fulminant yersiniosis due to the bacteria's siderophilic nature. Yersinia infection can be devastating in these patients, and early intervention with empiric antibiotics combined with targeted resuscitation can be essential in their care. The following case illustrates the utility for heightened surveillance, early intervention, and guided resuscitation in the management of this at-risk population.


Assuntos
Transfusão de Eritrócitos/efeitos adversos , Yersiniose/complicações , Yersinia enterocolitica/isolamento & purificação , Talassemia beta/complicações , Bacteriemia/etiologia , Criança , Humanos , Masculino , Yersiniose/diagnóstico , Yersiniose/transmissão , Talassemia beta/terapia
10.
Eur J Pharmacol ; 854: 398-405, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31039344

RESUMO

Hemoglobinopathies, such as ß-thalassemia, and sickle cell disease (SCD) are caused by abnormal structure or reduced production of ß-chains and affect millions of people worldwide. Hereditary persistence of fetal hemoglobin (HPFH) is a condition which is naturally occurring and characterized by a considerable elevation of fetal hemoglobin (HbF) in adult red blood cells. Individuals with compound heterozygous ß-thalassemia or SCD and HPFH have milder clinical symptoms. So, HbF reactivation has long been sought as an approach to mitigate the clinical symptoms of ß-thalassemia and SCD. Using CRISPR-Cas9 genome-editing strategy, we deleted a 200bp genomic region within the human erythroid-specific BCL11A (B-cell lymphoma/leukemia 11A) enhancer in KU-812, KG-1, and K562 cell lines. In our study, deletion of 200bp of BCL11A erythroid enhancer including GATAA motif leads to strong induction of γ-hemoglobin expression in K562 cells, but not in KU-812 and KG-1 cells. Altogether, our findings highlight the therapeutic potential of CRISPR-Cas9 as a precision genome editing tool for treating ß-thalassemia. In addition, our data indicate that KU-812 and KG-1 cell lines are not good models for studying HbF reactivation through inactivation of BCL11A silencing pathway.


Assuntos
Sistemas CRISPR-Cas/genética , Proteínas de Transporte/genética , Hemoglobina Fetal/metabolismo , Deleção de Genes , Terapia Genética/métodos , Proteínas Nucleares/deficiência , Proteínas Nucleares/genética , Talassemia beta/terapia , Sequência de Bases , Edição de Genes , Humanos , Células K562 , Proteínas Repressoras , Talassemia beta/genética , Talassemia beta/metabolismo , gama-Globinas/genética
11.
Eur J Haematol ; 103(2): 80-87, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31066943

RESUMO

OBJECTIVE: While doses of deferiprone up to 75 mg/kg/d have been demonstrated to be effective in cardiac iron removal, their efficacy in the reduction of liver iron has been equivocal. The aim of this study was to evaluate the effect of deferiprone dose on liver iron concentrations in adult iron overload patients. METHODS: A single-centered, retrospective, cohort observational study was conducted involving 71 patients exposed to deferiprone doses up to 113 mg/kg/d between January 2009 and June 2015 for a median of 33 months. RESULTS: At the end of the study period, liver iron measured by R2 MRI was reduced by a mean 1.7 mg/g dw. A dose effect was observed, with incremental reductions of 2.8 mg/g dw in end of study LIC for every 10 mg/kg/d higher dose of deferiprone (P < 0.001). A dose effect was also observed in end of study ferritin and cardiac iron concentration measured by T2* MRI (P < 0.0001 and P = 0.048, respectively). No associations between adverse effects and deferiprone dose were observed, but there was a trend toward higher rates of agranulocytosis at higher doses and two of three hereditary hemochromatosis patients developed this complication. CONCLUSION: The present study failed to demonstrate that the use of deferiprone at >90 mg/kg/d was associated with increased risk of agranulocytosis or neutropenia, but did demonstrate more effective liver iron control in iron overload patients.


Assuntos
Deferiprona/administração & dosagem , Quelantes de Ferro/administração & dosagem , Sobrecarga de Ferro/tratamento farmacológico , Ferro/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Adolescente , Adulto , Anemia Falciforme/complicações , Anemia Falciforme/diagnóstico , Anemia Falciforme/genética , Anemia Falciforme/terapia , Biomarcadores , Humanos , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Fígado/patologia , Imagem por Ressonância Magnética , Adesão à Medicação , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem , Talassemia beta/complicações , Talassemia beta/diagnóstico , Talassemia beta/genética , Talassemia beta/terapia
12.
Eur J Obstet Gynecol Reprod Biol ; 238: 38-43, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31082742

RESUMO

OBJECTIVE: Although spontaneous fertility and successful pregnancies have been reported in well-chelated and transfused women with beta thalassaemia major (BTM), majority of women are subfertile due to hypogonadotropic hypogonadism (HH). Little is known about the effect of iron overload on ovarian follicles and whether ovarian reserve is affected by the disease or treatment status. This study compares the markers of ovarian reserve in women with transfusion-dependent BTM over a period of ten years with healthy women from a control population. STUDY DESIGN: We performed a 10-year mixed (retrospective and prospective) longitudinal study in 17 women with transfusion-dependent BTM from our thalassaemia clinic between July 2007 to June 2017. The results were compared with 52 age-matched healthy women without any medical conditions (control population) attending our fertility clinic. Patient demographics, medical history, menstrual history, hormonal parameters (serum levels of FSH, estradiol, TSH and AMH) and antral follicle count were recorded in all women from both groups. Serum levels of ferritin, cardiac T2*, liver iron concentration, thyroid function (TSH) and liver function test results were also recorded at three different time points. RESULTS: Serum AMH levels, estradiol levels and antral follicle count were significantly lower in women with BTM compared with the control group (p < 0.05 for all). Low AMH levels were noted in both groups of women (with and without HH) with a background of BTM. Serum AMH levels positively correlated with AFC in women with BTM. CONCLUSION: Serum AMH level and AFC were significantly lower in women with transfusion dependent BTM as compared to age-matched healthy controls suggesting a direct impact of the disease activity or iron overload on the ovary.


Assuntos
Sobrecarga de Ferro/fisiopatologia , Reserva Ovariana , Talassemia beta/sangue , Adulto , Biomarcadores/sangue , Transfusão de Sangue , Estudos de Casos e Controles , Feminino , Humanos , Estudos Longitudinais , Talassemia beta/fisiopatologia , Talassemia beta/terapia
13.
Hemoglobin ; 43(1): 34-37, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31084365

RESUMO

ß-Thalassemia major (ß-TM) patients are at increased risk for cardiovascular diseases. Determination of subclinical cardiac involvement is essential for preventive measures. Thus, we aimed to evaluate the role of stress echocardiography for identification of subclinical cardiac dysfunction in ß-TM patients. In this prospective study, 45 ß-TM patients who were referred for cardiac evaluation, were enrolled. Exclusion criteria included non sinus rhythm and overt cardiac disease. Stress echocardiography levels and cardiac magnetic resonance imaging (MRI) results were obtained from ß-TM patients. Patients were divided into two groups of normal vs. iron overload from cardiac T2* greater or less than 20 msec, respectively. Resting and peak exercise right ventricular stroke volume (RVSV) and left ventricular SV (LVSV) were significantly lower in iron overload vs. normal ß-TM patients, respectively (p value <0.05). At peak LV global longitudinal strain (GLS) and myocardial performance index (MPI) were significantly decreased and increased compared with resting in iron overload vs. normal ß-TM patients, respectively (p value <0.05). There was a significant relationship between inappropriate hemodynamic response to exercise and lower age (p value = 0.032). Resting LVSV and RVSV seemed better prognosticators for iron overload than LV ejection fraction (LVEF). Decreased GLS and increased MPI at peak exercise could also predict the presence of cardiac iron overload. These measurements by stress echocardiography could be evaluated when cardiac T2* could not be determined.


Assuntos
Ecocardiografia sob Estresse , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Talassemia beta/complicações , Adolescente , Adulto , Ecocardiografia sob Estresse/métodos , Feminino , Cardiopatias/fisiopatologia , Testes de Função Cardíaca , Humanos , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda , Adulto Jovem , Talassemia beta/diagnóstico , Talassemia beta/terapia
15.
Postgrad Med ; 131(4): 261-267, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31002266

RESUMO

Despite the advances in the management of thalassemia major, heart disease remains the leading cause of mortality in patients afflicted with this disorder. Cardiac involvement in thalassemia encompasses a spectrum of disorders including myocardial dysfunction, arrhythmias, pulmonary hypertension, and peripheral vascular disease. Although cardiac siderosis (accumulation of iron in cardiac myocytes) as a consequence of repeated blood transfusions is deemed to be the main etiologic factor for myocardial dysfunction in transfusion-dependent patients, the significance of other pathophysiologic mechanisms is being increasingly recognized especially in non-transfusion dependent patients. Management of cardiac complications in thalassemia major hinges on the treatment of the underlying pathophysiology, which often is unmitigated iron overload. The prevalence and predictors of cardiac complications in 'ex-thalassaemics' [thalassaemic patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) is unknown at present. In this review, we look at the pathogenesis of cardiac involvement in patients with beta-thalassemia major, the advances in the management of these patients and the future prospects.


Assuntos
Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Talassemia beta/complicações , Talassemia beta/fisiopatologia , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Transfusão de Sangue/métodos , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Testes de Função Cardíaca , Hemoglobinas/metabolismo , Humanos , Sobrecarga de Ferro/fisiopatologia , Talassemia beta/terapia
16.
Ann Biol Clin (Paris) ; 77(2): 169-173, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30998197

RESUMO

OBJECTIVE: Thalassemias is the consequence of a synthesis imbalance between the α and ß chains of hemoglobin. It's a hereditary haemolytic anemias, which presents a problem of public health because of their frequency and the difficulties of their care. The objective of this work is to study the epidemiological, clinico-biological, therapeutic and evolutionary profile of thalassemic patients in Morocco. METHODS: We're reporting the results of a retrospective multicenter study on all cases of thalassemia taken at the hospitals: Avicenne military hospital in Marrakech, Mohammed VI hospital in Marrakech and the regional center for blood transfusion in Agadir. RESULTS: During this period we collected 81 cases of thalassemias. The average age was 13 years (from 1 month to 60 years) with a sex ratio (M/F) of 0.8. The reason for consultation was anemia in 43% of cases. The electrophoresis of hemoglobin has shown a predominance of the ß-thalassemia minor form. On the evolutionary level, iron overload and endocrine complications were the most frequent. CONCLUSION: The development of a prevention program based mainly on health education, the reduction of consanguineous marriages and genetic counseling, are probably the main ways of combating the emergence of new thalassemic cases.


Assuntos
Talassemia beta/diagnóstico , Talassemia beta/epidemiologia , Talassemia beta/terapia , Adolescente , Adulto , Transfusão de Sangue/métodos , Transfusão de Sangue/estatística & dados numéricos , Criança , Pré-Escolar , Progressão da Doença , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Marrocos/epidemiologia , Estudos Retrospectivos , Adulto Jovem , Talassemia beta/patologia
17.
Pediatr Hematol Oncol ; 36(3): 151-160, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31032672

RESUMO

ß-Thalassemia, a blood disease instigated by mutations in ß-globin genes or their regulatory regions. Infectious complications, immune abnormalities and iron overload related organ damage are the chief causes of morbidity and mortality. The role of inflammatory cytokines in the pathophysiology of ß-thalassemia is still indistinct, so the present study aimed to evaluate immune-inflammatory and redox status in ß-thalassemia and their relation to iron status, frequency/duration of blood transfusion. Seventy ß-Thalassemia patients (35 ß-thalassemia major; 35 ß-thalassemia intermedia) and twenty age and sex-matched healthy controls were included. Interleukin4 (IL4), Interleukin10 (IL10), Interleukin 8 (IL8), and Interleukin 13 (IL13) levels were immunoassayed in addition to iron, hematological and redox status assessment. Significantly increased iron, ferritin, IL8, IL13 levels (p value ˂0.001), meanwhile, decreased IL10 level, total anti-oxidant (TAC) and iron binding capacities were observed in ß-thalassemia major compared with ß-thalassemia intermedia and control groups (p value ˂0.001) . IL4 level was decreased in patients group compared to control. Positive correlation was found between malondialdehyde (MDA), IL8, IL13 and iron load, transfusion frequency/duration, total leucocyte count and lymphocyte (%). Meanwhile, negative correlation was found with IL4, IL10, and TAC. Multiple blood transfusions increased iron stores which may critically impair the immune-regulatory balance with disturbed redox status and cytokine profile.


Assuntos
Transfusão de Sangue , Citocinas/sangue , Ferro/sangue , Talassemia beta/sangue , Talassemia beta/terapia , Adolescente , Criança , Feminino , Humanos , Masculino , Oxirredução
18.
Blood Cells Mol Dis ; 77: 67-71, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30978615

RESUMO

BACKGROUND: In patients with thalassemia major, examination routinely used for the evaluation of iron load in Indonesia is serum ferritin, but it is strongly influenced by other factors such as infections, inflammation and vitamin C levels. Evaluation of urinary iron excretion is an important and easy method to indicate iron chelation efficacy. OBJECTIVE: To determine the efficacy of iron chelation therapy by urinary iron examination and to evaluate its correlation with the time of transfusion, serum ferritin level, transferrin saturation and T2* MRI. METHODS: Prospective cohort study was conducted in children with thalassemia major aged 7-<18 years old who received DFP therapy. Twenty-four-hour urine collections were examined through inductively coupled plasma - mass spectrometry (ICP-MS). Patient's serum ferritin, transferrin saturation, peripheral blood, differential count and T2* MRI was documented during the study. Data analysis is based on urine iron level, body iron balance and the correlation between urine iron level, serum ferritin, transferrin saturation and T2* MRI and dosage of DFP. RESULTS: Thirty (55%) subjects showed a higher urine iron level on the day prior to transfusion (mean: 12,828 SD ±12,801 µg/24 h) in comparison to post transfusion (mean: 10,985 SD ±10,023 µg/24 h). All subjects had positive iron balance (mean 524 SD ±230 mg). There were positive correlation between urine iron level and transferrin saturation (r = 0.559, p = 0.01) and serum ferritin (r = 0.291, p = 0.03), no correlation found with T2* MRI results. CONCLUSIONS: There is a relationship to urinary iron excretion in response to chelation therapy and the degree of iron load.


Assuntos
Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/urina , Ferro/urina , Talassemia beta/complicações , Adolescente , Biomarcadores , Transfusão de Sangue , Terapia por Quelação , Criança , Feminino , Ferritinas/sangue , Humanos , Quelantes de Ferro/farmacologia , Sobrecarga de Ferro/diagnóstico , Sobrecarga de Ferro/etiologia , Imagem por Ressonância Magnética , Masculino , Resultado do Tratamento , Urinálise , Talassemia beta/terapia
19.
J Pediatr Hematol Oncol ; 41(5): e296-e301, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30933028

RESUMO

Thalassemia is a major public health problem in developing countries. Sibling matched hematopoietic stem cell transplantation (HCT) is the recommended treatment for thalassemia major (TM). We retrospectively analyzed our data of thalassemia major patients who underwent HCT at a tertiary care center in Northern India from January 2008 to September 2017. The primary end points were overall survival (OS) and thalassemia-free survival (TFS), and secondary end points were complications post HCT (graft-versus-host-disease [GVHD], hemorrhagic cystitis [HC], and sinusoidal obstruction syndrome [SOS]). Data of 203 transplants for 200 patients (3 s transplants) were evaluated. Median follow-up period was 29.1 months (range, 0.3 to 116.7 mo). The overall survival (OS) was 88.5% and TFS was 82%. Class risk analysis showed a significantly higher OS and TFS in class I and class II compared to class III high risk group (OS: P=0.0017; TFS: P=0.0005) and (OS: P=0.0134; TFS: P=0.0027) respectively. Acute and chronic GVHD was seen in 59 (29.5%) and 18 (9%) patients, respectively, and SOS and HC were seen in 23 (11.5%) and 11 (5.5%) patients, respectively. This study reconfirms that allogenic HCT is feasible in developing world with the overall survival and TFS comparable to that reported in Western literature and should be considered early in all TM patients with available matched sibling donors.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Talassemia beta/terapia , Adulto , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/etiologia , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Irmãos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Talassemia beta/complicações , Talassemia beta/mortalidade
20.
Hematology ; 24(1): 426-438, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30947625

RESUMO

OBJECTIVES: Beta-thalassemias are a group of recessively autosomal inherited disorders of hemoglobin synthesis, which, due to mutations of the beta-globin gene, lead to various degrees of defective beta-chain production, an imbalance in alpha/beta-globin chain synthesis, ineffective erythropoiesis, and anemia. Improved survival in thalassemic patients has led to the emergence of previously unrecognized complications, such as renal disease. METHODS: A comprehensive literature review through PubMed was undertaken to summarize the published evidence on the epidemiology and pathophysiology of renal disease in thalassemia. Literature sources published in English since 1990 were searched, using the terms beta-thalassemia, renal disease. RESULTS: Renal disease is considered to be the 4th cause of morbidity among patients with transfusion dependent thalassemia. Chronic anemia, hypoxia and iron overload are the main mechanisms implicated in development of renal injury, whereas several studies also suggested a contributive role of iron chelators. DISCUSSION AND CONCLUSION: Kidney disease may develop through progressive renal tubular and glomerular damage; thus, its early recognition is important in order to prevent and/or reverse deterioration. This review will provide an insight on the involved mechanisms implicated in kidney disease in thalassemic patients and will discuss the updates on diagnosis and prevention of renal complications in thalassemia.


Assuntos
Hipóxia , Sobrecarga de Ferro , Nefropatias , Talassemia beta , Feminino , Humanos , Hipóxia/complicações , Hipóxia/metabolismo , Hipóxia/mortalidade , Hipóxia/terapia , Sobrecarga de Ferro/complicações , Sobrecarga de Ferro/metabolismo , Sobrecarga de Ferro/mortalidade , Sobrecarga de Ferro/terapia , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/mortalidade , Nefropatias/terapia , Masculino , Talassemia beta/complicações , Talassemia beta/metabolismo , Talassemia beta/mortalidade , Talassemia beta/terapia
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