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.

Thalassemia, a human blood disorder / Talassemia, uma doença do sangue humano

Abstract A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Resumo Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados ​​em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, já que os cientistas ainda não conseguiram encontrar uma cura permanente para essa doença mortal depois de mais de 87 anos desde que foi descrita pela primeira vez em 1925.

Thalassemia, a human blood disorder / Talassemia, uma doença do sangue humano

A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.

Um grupo de defeitos sanguíneos hereditários é conhecido como talassemia e está entre as hemoglobinopatias mais prevalentes do mundo. As talassemias são de dois tipos, como talassemia alfa e beta. As causas desses defeitos são as mutações genéticas que levam a níveis baixos e/ou proteínas de globina com mau funcionamento, respectivamente. Em alguns casos, uma dessas proteínas pode estar completamente ausente. As cadeias de globina α e β formam uma dobra ou bolsa de globina para a fixação de heme (Fe ++) para transportar oxigênio. Os genes das proteínas alfa e beta globina estão presentes na forma de um cluster nos cromossomos 16 e 11, respectivamente. Diferentes genes de globina são usados em diferentes estágios do curso de vida. Durante os estágios de desenvolvimento embrionário e fetal, as proteínas γ globina se associam à α globina e, posteriormente, são substituídas pela proteína β globina. Os desequilíbrios da cadeia de globina resultam em hemólise e impedem a eritropoiese. Indivíduos que apresentam sintomas leves incluem portadores de talassemia alfa ou as pessoas com traços de talassemia alfa ou beta. A talassemia alfa causa condições como anemia hemolítica ou hidropsia fetal fatal, dependendo da gravidade da doença. A beta talassemia principal resulta em anemia hemolítica, retardo de crescimento e aberrações esqueléticas na primeira infância. As crianças afetadas por esse distúrbio precisam de transfusões de sangue regulares ao longo da vida. Os pacientes que dependem de transfusão de sangue geralmente desenvolvem sobrecarga de ferro que causa outras complicações nos sistemas do corpo, como insuficiência renal ou hepática, portanto as talassemias agora são classificadas como uma síndrome. A única cura para as talassemias seria um transplante de medula óssea ou terapia genética sem atualmente uma taxa de sucesso significativa. Uma compreensão completa da base molecular dessa síndrome pode fornecer novos insights e ideias para seu tratamento, [...].

Hemoglobinopathy and pediatrics in the time of COVID-19

ABSTRACT Introduction: It is important to know if patients with hemoglobinopathy could be more susceptible to COVID-19. Objective: Analyze SARS-CoV-2 infection in pediatric patients with hemoglobinopathy. Methods: Using the online platforms LILACS, PUBMED and EMBASE, on 17- JUL-2020 a search was made for the terms COVID-19 and SARS-CoV-2 associated with "sickle cell", "thalassemia" and "hemoglobinopathy". Results: There were 623 pediatric and adult patients with sickle cell disease (SCD) or beta thalassemia (BT) and COVID-19. Total mortality rate was 6.42%. No pediatric patient with BT has been described. So, our analysis focused on children and adolescents with SCD: there were 121 pediatric patients, one adolescent died, prophylactic anticoagulation was prescribed to six patients, 11.76% needed intensive care unit, blood transfusion was prescribed in 29.70%. Vaso-occlusive crisis (VOC) and acute chest syndrome (ACS) were the main clinical manifestations in SCD. Discussion: Pediatric patients with SCD and COVID-19 have a low mortality rate when compared to adults, although is higher than the global pediatric population with COVID-19 (0−0.67%). The comorbidities associated with age and the long-term complications inherent to hemoglobinopathies may contribute to the increased mortality outside the pediatric age group. In SCD the clinical manifestations, both in children and adults, are VOC and ACS, and there was increase in blood requirement. Pediatric SCD patients with COVID-19 need more intensive care unit than the global pediatric population (3.30%). Conclusion: Despite pediatric population with SCD needs more intensive care, the outcome after infection by COVID-19 is favorable.

Manifestações orofaciais associadas aos diferentes tipos de anemias / Orofacial manifestations associated with different types of anemia

Introduction: Anemias correspond to hematological disorders that can present in the oral cavity and face. Objective: To review the literature on the main types of anemic disorders and their orofacial manifestations, considering the aspects of interest to dentists. Methodology: This is a literature review, in which articles were selected in Portuguese and English, indexed in the Scielo, Medline/Pubmed and Lilacs databases with the descriptors: Anemia, Oral Manifestations, Jaw Abnormalities and their correspondents in Portuguese language. Literature review: Anemic disorders associated with orofacial signs and symptoms include mainly Iron-Deficiency, Megaloblastic, Fanconis, Sickle Cell, Thalassemia and Aplastic Anemia. The manifestations vary from burning and painful symptoms in the tongue, pallor of lips and mucosa, stomatitis, atrophic glossitis, angular cheilitis, susceptibility to candidiasis and peri-odontal disease. Also, dental changes, hyposalivation, malocclusion, osteomyelitis of the jaw, paraesthesia of the mental nerve and orofacial pain are included. Conclusion: These manifestations can be the first signs of the presence of anemia, which gives the dentist an important role in early diagnosis and proper management of dental treatment.

Introdução: As anemias correspondem a distúrbios hematológicos que podem apresentar manifestações na cavidade oral e face. Objetivo: Revisar a literatura acerca dos principais tipos de distúrbios anêmicos e suas manifestações orofaciais, considerando os aspectos de interesse aos cirurgiões-dentistas. Metodologia: Trata-se de uma revisão de literatura, em que foram selecionados artigos em português e inglês, indexados nas bases de dados do Scielo, Medline/Pubmed e no Lilacs, com os descritores: Anemia, Oral Manifestations, Jaw Abnormalities e seus correspondentes na língua portuguesa. Revisão de literatura: Os distúrbios anêmicos associados aos sinais e sintomas orofaciais incluem principalmente a Anemia Ferropriva, Megaloblástica, de Fanconi, Falciforme, Talassemia e Anemia Aplástica. As manifestações variam de ardência e sintomatologia dolorosa em língua, palidez de lábios e mucosa, estomatite, glossite atrófica, queilite angular, suscetibilidade a candidíase e doença periodontal. Ainda, englobam-se as alterações dentárias, hipossalivação, má oclusão, osteomielite da mandíbula, parestesia do nervo mental e dor orofacial. Conclusão: Essas alterações podem ser os primeiros sinais da presença da anemia, o que confere ao cirurgião-dentista um importante papel no seu diagnóstico precoce e condução adequada ao tratamento odontológico.

Identificação de anemias na infância em um hemocentro no sul do Brasil / Identification of anemias in childhood in a hemocenter in southern Brazil

Introdução: as anemias adquiridas ocasionadas pela deficiência de diversos micronutrientes têm a deficiência de ferro como principal causa. Das causas congênitas, as hemoglobinopatias, doença falciforme e talassemias são as mais prevalentes. Objetivo: identificar a frequência das anemias falciforme, ferropriva e talassemia, no Hemocentro de Maringá, Paraná. Método: trata-se de estudo transversal realizado prospectivamente a partir dos registros de atendimentos de crianças de zero a dez anos de idade incompletos e sua correlação com idade e sexo, de 2017 e 2018. Resultados: no grupo como um todo, observou-se maior número de lactentes (41,67%) e proporção semelhante entre sexos. A anemia ferropriva foi a mais frequente, seguida da beta talassemia minor, da anemia falciforme e do traço falciforme. Analisando a correlação dos tipos de anemia com sexo (Brown-Forsythe test) e idade (Bartlett's test) obteve-se diferença estaticamente significante (p<0,0001) entre essas variáveis e os tipos de anemia. Conclusão: chama atenção o percentual elevado de anemia ferropriva encaminhando para atenção secundária. Sugerem-se outros estudos, que possam elucidar os fatores etiológicos da elevada proporção de casos de anemia ferropriva, principalmente em lactentes, os quais devem receber profilaxia para prevenção desse tipo de anemia.

Introduction: Acquired anemia caused by the deficiency of several micronutrients has iron deficiency as the main cause. Of the congenital causes, hemoglobinopathies, sickle cell disease and thalassemia are the most prevalent. Objective: To identify the frequency of sickle cell anemia, iron deficiency and thalassemia in the Maringá Hemocenter, Paraná. Method: This was a cross-sectional study conducted prospectively from the records of care of children from zero to ten years old and its correlation with age and gender, from 2017 and 2018. Results: in the group as a whole, we observed higher number of infants (41.67%) and similar sex ratio. Iron deficiency anemia was the most frequent, followed by Beta Thalassemia Minor, Sickle Cell Anemia and Sickle Cell Trace. Analyzing the correlation of anemia types with sex (Brown-Forsythe test) and age (Bartlett's test), a statistically significant difference (p <0.0001) was found between these variables and anemia types. Conclusion: the high percentage of iron deficiency anemia calls for secondary attention. Other studies are suggested that may elucidate the etiological factors of the high proportion of iron deficiency anemia cases, especially in infants, who should receive prophylaxis to prevent this type of anemia.

Epidemiology and risk factors of transfusion transmitted infections in thalassemia major: a multicenter study in Pakistan

ABSTRACT Background: Blood transfusion-transmitted infections in individuals suffering from beta-thalassemia have been reported in Pakistan, but the information on their sociodemographic and clinical determinants is lacking. This study aims to describe the prevalence, as well as the factors, contributing in blood transfusion-transmitted infections. Method: Between December 2011 and December 2013, in a non-probable sampling, 350 thalassemia patients were recruited in Lahore, Multan, Karachi and Peshawar, Pakistan. Subjects were screened for transfusion-transmitted infections. Results: A seropositive rate of 36.5% was observed; males (94, 73.4%) and females (34, 26.6%). Among several risk factors associated with transfusion-transmitted infections, province (p = 0.001), gender (p = 0.003), age (p < 0.03), education (p < 0.00), degree of consanguinity (p = 0.05), age at fetal blood test (p = 0.005), fetal hemoglobin levels (p = 0.005), death due to thalassemia (p = 0.001) and iron-related complications (p = 0.04) showed significant correlation. Participants with an age >10 years were significantly more prone to seropositivity than those aged ≤10 years. Moreover, the ferritin level was also significantly higher in those aged >10 years than in those ≤10 years. It was observed that males had a higher seroprevalence rate (94, 73.4%) than females (34, 26.6%). The most prevalent transfusion-transmitted infections was the hepatitis C virus, with 115 cases (89.8%). Conclusion: A high prevalence rate of HCV in subjects with transfusion-dependent thalassemia is linked with insufficient facilities, poor management and compromised socioeconomic status. Therefore, more multicenter studies covering cities from different regions of the country are needed in order to develop preventive measurements at the regional and national level.

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

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

Hemoglobinopatías y Malaria. ¿Están protegidos? / Hemoglobinopathies and Malaria. They are protected?

Se presenta el caso de un paciente femenina de 9 años procedente de Puerto Obaldía en la Comarca Guna Yala con heterocigocidad para HbS/Talasemia beta y parasitación por Plasmodium vivax.

We present the case of a 9-year-old female patient from Puerto Obaldía in the Comarca Guna Yala with heterozygosity for HbS / beta thalassemia and parasitism by Plasmodium vivax

Estudo da associação entre talassemia alfa e doença falciforme em pacientes do hemocentro regional de Montes Claros / Study of the association between alpha thalassemia and falciform disease in patiensts of the hemocentro regional de Montes Claros

OBJETIVO: Avaliar a coexistência da talassemia alfa (a-Tal) e sua interferência no curso clínico dos pacientes com Doença Falciforme no Hemocentro Regional de Montes Claros-MG. Metodologia: Estudo transversal analítico, com amostra aleatorizada, na qual foram incluídos pacientes triados pelo Programa Estadual de Triagem Neonatal de Minas Gerais e encaminhadas ao Hemocentro Regional de Montes Claros, com perfil eletroforético compatível com anemia falciforme, nascidos no período entre 26/01/2000 e 13/05/2014. Os dados clínicos dos pacientes foram coletados nos prontuários médicos do Ambulatório do Hemocentro Regional de Montes Claros. A genotipagem de a-Tal foi realizada por PCR multiplex (alelos: -a3.7; -a4.2; --SEA; --FIL; --MED; -(a) 20.5 e --THAI) no Serviço de Pesquisa Serviço de Pesquisa da Fundação Hemominas. Os dados foram analisados em teste estatísticos qui-quadrado em Software SPSS versão 16.0. Resultados: Foram estudados 50 pacientes, sendo 25 (50%) do sexo masculino e 25 (50%) do sexo feminino. A idade dos pacientes variou de 9 meses a 15 anos de idade. A prevalência da a-Tal foi de 30%. Não houve associação estatística significativa entre a presença de a-Tal e infecção, internação, crises álgicas, sequestro esplênico, esplenectomia, transfusão sanguínea e Acidente Vascular Cerebral (AVC). No entanto, a frequência de crises álgicas, esplenectomia e AVC foi menor nos pacientes que apresentavam coexistência da a-Tal. Conclusões: A prevalência de a-Tal em indivíduos com anemia falciforme no nosso estudo foi 30%. Algumas manifestações graves da AF ocorreram de forma menos frequente nos pacientes com a interação da a-Tal/anemia falciforme. (AU)

Objective: To evaluate the coexistence of alpha thalassemia (a-Tal) and its interference in the clinical course of patients with sickle cell disease at Hemocentro Regional de Montes Claros-MG. Methodology: This is a cross-sectional, analytical study with a randomized sample carried out with patients screened by the State Neonatal Screening Program of Minas Gerais and referred to the Hemocentro Regional de Montes Claros with an electrophoretic profile compatible with sickle cell anemia, born between 01.26.2000 and 05.13.2014. The clinical data of the patients were collected in the medical records of the Outpatient Clinic of the Hemocentro Regional de Montes Claros. The a-Tal genotyping was performed by multiplex PCR (alleles: -a3.7; -a4.2; --SEA; --FIL; --MED; - (a) 20.5 and --THAI) in the Research Service Fundação Hemominas. The data were analyzed in chi-square statistical test in SPSS Software version 16.0. Results: Fifty patients were studied, 25 (50%) were male, and 25 (50%) were female. Patients´ ages ranged from 9 months to 15 years old. The prevalence of a-Tal was 30%. There was no significant statistical association between the presence of a-Tal and infection, hospitalization, painful crises, splenic sequestration, splenectomy, blood transfusion and cerebrovascular accident (CVA). However, the frequency of painful seizures, splenectomy and CVA was lower in patients with a-Tal coexistence. Conclusions: The prevalence of a-Tal in individuals with sickle cell anemia in our study was 30%. Some severe manifestations of SCA occurred less frequently in patients with a-Tal/sickle cell anemia interaction. (AU)

Detección de anticuerpos contra Trypanosoma cruzi en pacientes multitransfundidos, Colombia / Detection of Trypanosoma cruzi antibodies in multitransfused patients in Colombia

Resumen Introducción. La enfermedad de Chagas es un problema de salud pública en Latinoamérica y, aunque la transmisión vectorial es la más importante, deben evaluarse otras formas de transmisión, como la de las transfusiones. Objetivo. Describir la prevalencia de infección con Trypanosoma cruzi en pacientes sometidos a múltiples transfusiones o multitransfundidos. Materiales y métodos. Se detectaron anticuerpos IgG contra T. cruzi mediante dos inmunoensayos en muestras tomadas de pacientes sometidos a múltiples transfusiones en cuatro hospitales de Bogotá y Medellín, Colombia. Se analizó la asociación de factores de riesgo conocidos y se calcularon las razones de momios (odds ratio, OR) con un intervalo de confianza de 95 % (IC) utilizando el programa Stata 11(tm). Resultados. Se evaluaron 479 muestras. La prevalencia de anticuerpos contra T. cruzifue de 1,88 % (nueve pacientes): cinco pacientes remitidos de oncohematología, dos de hemodiálisis, uno tenía talasemia y uno había sufrido pérdida súbita y abundante de sangre. No se halló ningún paciente con hemofilia que resultara positivo, ni relación de los factores de riesgo de infección asociados con la transfusión de componentes sanguíneos, como el número de transfusiones, la cantidad de unidades de sangre y el tipo de componente, con la presencia de anticuerpos anti-T. cruzi. Solo se encontró relación entre la infección con el virus de la hepatitis C y la presencia de anticuerpos anti-T. cruzi (OR=5,68; IC95% 1,36-23,63). Conclusión. La frecuencia de infección por T. cruzi hallada en este grupo de pacientes sugiere que el riesgo de infección por transfusiones en Colombia es bajo. No se encontró relación entre los factores de riesgo asociados con la transfusión y la presencia de anticuerpos anti-T. cruzi.

Abstract Introduction: Chagas disease is a public health problem in Latin America. Even though vector-borne infection is the most important transmission mode for this disease, other modes such as transfusions require evaluation. Objective: To describe the prevalence of T. cruzi infection in multitransfused patients. Materials and methods: We detected IgG antibodies against T. cruzi by two immunoassays in samples from multitransfused patients in four hospitals located in Bogotá and Medellín, Colombia. We analyzed the association with known risk factors, and we calculated the odds ratios (OR) with 95% confidence intervals using Stata 11(tm) statistical software. Results: In total, 479 samples were tested. Overall, T. cruzi antibody prevalence was 1.88% (nine patients). Five were onco-hematological patients, two were hemodialyzed, one had thalassemia, and one had suffered acute blood loss. We found no hemophilia patients. There was no association between known risk factors for transfusion-transmitted infection (such as the number of transfusion events, number of blood units and type of blood component) and the presence of anti-T. cruzi antibodies in this study. Only the hepatitis C virus infection showed a positive association with the presence of anti-T. cruzi antibodies (OR=5.68, 95% CI: 1.36-23.63). Conclusions: The results of this study showed a low frequency of T. cruzi infection in multitransfused patients, suggesting that the risk of transfusion infection in Colombia is low. Known risk factors for transfusion-related infection were not associated with the presence of anti-T. cruzi antibodies.

Técnicas convencionales aplicadas al diagnóstico de las hemoglobinopatías / Conventional techniques applied to the diagnosis of hemoglobinopathies / Técnicas convencionais aplicadas ao diagnóstico das hemoglobinopatias

Las hemoglobinopatías son trastornos hereditarios debidos a una gran variedad de defectos que afectan a los genes de globina. El diagnóstico de las hemoglobinopatías resulta de una combinación de estudios clínicos, pruebas de laboratorio y estudio familiar. Las herramientas básicas incluyen hemograma, hemoglobina e índices eritrocitarios (VCM, HCM), morfología de los eritrocitos, recuento de reticulocitos y perfil de hierro. Las determinaciones complementarias son electroforesis de hemoglobina que permite separar las diferentes variantes de acuerdo con su carga eléctrica, cuantificación de hemoglobina A2 (HbA2), Fetal (Hb F), pruebas de solubilidad hemoglobínica y falciformación. Otras técnicas se basan en propiedades fisicoquímicas como la estabilidad de la hemoglobina para detección de variantes inestables. En la práctica las pruebas más útiles son las que permiten detectar la presencia de hemoglobinopatías, como ocurre con la hemoglobina S dejando para laboratorios especializados aquellos procedimientos para identificar la mutación. La correcta detección de los portadores de las diferentes hemoglobinopatías tiene como finalidad dar un consejo genético adecuado sobre la forma de herencia, el riesgo de tener hijos afectados con las formas graves de la enfermedad y evitar tratamientos innecesarios. El diagnóstico molecular se reserva para la alfa talasemia, para cuadros con genotipos complejos, estudios prenatales o epidemiológicos.

Hemoglobinopathies are hereditary syndromes determined by a large variety of globin gene defects. Hemoglobinopathy diagnosis results from the combination of clinical orientation, laboratory tests and family studies. Basic tools include complete blood cell count, red blood cell count, hemoglobin quantification and red cell indices (MCV, MCH), blood film examination, reticulocyte count and iron status. Complementary determinations are hemoglobin electrophoresis, which enables the separation of the different hemoglobin variants according to their electrical charge, A2, and Fetal hemoglobin quantification, hemoglobin solubility and sickling test for Hb S diagnosis. Other techniques are based on physicochemical properties such as stability of hemoglobin for detection of unstable variants. In practice, the most useful tests are those that enable the detection of hemoglobinopathies, such as hemoglobin S, and the identification of the genetic defects is referred to specialized laboratories. The correct detection of the carriers of the different hemoglobinopathies is intended to give adequate genetic advice on the form of inheritance and the risk of having affected children with the severe forms of the disease and to avoid unnecessary treatments. Molecular diagnosis is reserved to a thalassemia complex genotypes, prenatal o epidemiological studies.

As hemoglobinopatias são distúrbios hereditários resultantes de uma grande variedade de defeitos que afetam os genes de globina. O diagnóstico das hemoglobinopatias decorre de uma combinação de estudos clínicos, provas de laboratório e estudo familiar. As ferramentas básicas incluem hemograma, hemoglobina e índices eritrocitários (VCM, HCM), morfologia dos eritrócitos, contagem de reticulócitos e perfil de ferro. As determinações complementares são eletroforese de hemoglobina que permite separar as diferentes variantes, de acordo com sua carga elétrica, quantificação de hemoglobina A2 (HbA2), Fetal (Hb F), provas de solubilidade hemoglobínica e falciformação. Outras técnicas baseiam-se em propriedades fisicoquímicas como a estabilidade da hemoglobina para detecção de variantes instáveis. Na prática, as provas mais úteis são as que permitem detectar a presença de hemoglobinopatias, como acontece com a hemoglobina S deixando para laboratórios especializados aqueles procedimentos para identificar a mutação. Detectar corretamente os portadores das diferentes hemoglobinopatías visa a dar um conselho genético adequado sobre a forma de herança, o risco de ter filhos afetados com as formas graves da doença e evitar tratamentos desnecessários. O diagnóstico molecular se reserva para a alfa talassemia, para quadros com genótipos complexos, estudos pré-natais ou epidemiológicos.

Talasemias: Aspectos clínicos / Thalassemias: Clinical aspects / Talassemias: Aspectos clínicos

Los síndromes talasémicos, junto con las hemoglobinopatías talasémicas, las hemoglobinopatías estructurales y los síndromes de sobreexpresión representan las diferentes formas clínicas de las hemoglobinopatías. Los defectos genéticos responsables de los síndromes talasémicos determinan la síntesis disminuída o nula de la cadena de globina correspondiente. Según la cadena cuya síntesis es defectuosa, los síndromes talasémicos se clasifican en a-talasemias, b-talasemias, etc. Según las diferentes combinaciones de fenotipos particulares, las a-talasemias se clasifican en silente, portador, enfermedad con hemoglobina H e hidropesía fetal, y las b-talasemias en menor, intermedia y mayor. La sospecha diagnóstica de los síndromes talasémicos leves y de las hemoglobinopatías talasémicas es fácil a partir de la anemia leve con marcada microcitosis hipocrómica, ausencia indudable de ferropenia y cuadro familiar positivo. La electroforesis de hemoglobina con una cuantificación de hemoglobina A2 mayor de 3,5% prácticamente confirma el diagnóstico de una b-talasemia menor, mientras que una hemoglobina A2 normal o disminuida va a hacer sospechar una a-talasemia leve cuyo diagnóstico debe ser confirmado por estudio de ADN. Una vez establecida la condición talasémica del propósito es imprescindible identificar qué familiares consanguíneos son o no portadores del mismo gen talasémico, y estudiar a los cónyuges de los talasémicos detectados, a fin de prever, a través del consejo genético, el nacimiento de hijos homocigotas o doble heterocigotas con formas más severas de talasemias o hemoglobinopatías.

Thalassemic syndromes, together with thalassemic hemoglobinopathies, structural hemoglobinopathies and over-expression syndromes represent the different clinical presentations of hemoglobinopathies, which are the mutational or deletional defects of globin genes. Genetic defects responsible for thalassemic syndromes determine a reduced or a lack of synthesis of the related chain. According to the defective synthesized chain, thalassemias are classified into a-thalassemias, b-thalassemias, etc. Depending on the different combinations of two or more phenotypes, a-thalassemias are classified into silent, carrier, Hb H disease and fetal hydrops, while b-thalassemias are classified into minor, intermediate and major b-thalassemia. Diagnostic suspicion of mild thalassemic syndromes and thalassemic hemoglobinopathies is easy based on a mild anemia with pronounced microcytosis and hypochromia, unquestionable absence of iron deficiency and positive family background. Hemoglobin electrophoresis with A2 hemoglobin level higher than 3.5% almost confirms a b-thalassemia minor, while a low or normal A2 hemoglobin level makes mild a-thalassemia suspicious and diagnosis must be confirmed by DNA study. Once the thalassemic condition of the propositus is confirmed, it is essential to identify which consanguineous relatives are or are not carriers of the same thalassemic gene, and then to study the couples of all already identified thalassemic relatives, in order to forecast, through genetic counselling, the birth of homozygous or double heterozygous children with more severe thalassemic or hemoglobinopathic conditions.

As síndromes talassêmicas, junto com as hemoglobinopatias talassêmicas, as hemoglobinopatias estruturais e as síndromes de sobre-expressão representam as diferentes formas clínicas das hemoglobinopatias. Os defeitos genéticos responsáveis pelas síndromes talassêmicas determinam a síntese diminuída ou nula da cadeia de globina correspondente. Segundo a cadeia cuja síntese é defeituosa, as síndromes talassêmicas são classificadas em a-talassemias, b-talassemias, etc. Conforme as diferentes combinações de fenótipos particulares, as a-talassemias são classificadas em silente, portador, doença com hemoglobina H e hidropesia fetal, e as b-talassemias em menor, intermediária e maior. A suspeita diagnóstica das síndromes talassêmicas leves e das hemoglobinopatias talassêmicas é fácil a partir da anemia leve com marcada microcitose hipocrômica, ausência induvidável de ferropenia e quadro familiar positivo. A eletroforese de hemoglobina com uma quantificação de hemoglobina A2 maior de 3,5% praticamente confirma o diagnóstico de uma b-talassemia menor, ao passo que uma hemoglobina A2 normal ou diminuída vai fazer suspeitar uma a-talassemia leve cujo diagnóstico deve ser confirmado por estudo de DNA. Assim que é estabelecida a condição talassêmica do propósito, é imprescindível identificar quais são os familiares consanguíneos e quais não são portadores do mesmo gene talassêmico, e estudar os cônjuges dos talassêmicos detectados, visando a prever, através do conselho genético, o nascimento de filhos homozigotas ou duplo-heterozigotas com formas mais severas de talassemias ou hemoglobinopatias.

Bases moleculares de hemoglobinopatías en Argentina / Molecular basis of hemoglobinopathies in Argentina / Bases moleculares de hemoglobinopatias na Argentina

Durante el desarrollo de un individuo se expresan distintas cadenas de globina de tipo a y no-a, que se combinan en tetrámeros para formar hemoglobina. Los genes que las codifican se organizan en familias. Distintas mutaciones afectan los genes que codifican las cadenas de globina: si provocan alteraciones cualitativas originan cuadros de hemoglobinopatías estructurales, si disminuyen las síntesis de las cadenas de globina, talasemias, y si tienen ambos efectos, hemoglobinopatías talasémicas. El propósito de este trabajo es presentar las bases moleculares de las hemoglobinopatías en Argentina, en un total de 862 muestras, en base a los estudios moleculares realizados en este laboratorio a partir del estudio de 910 muestras de pacientes. En nuestro medio, la Hb S es la hemoglobinopatía estructural más frecuente, las ß-talasemias presentan una distribución similar a la cuenca del Mediterráneo y las a-talasemias están intrínsecamente relacionadas a la ascendencia de los afectados. Las bases moleculares de las hemoglobinopatías son variadas. Mientras que en las hemoglobinopatías estructurales y ß-talasemias predominan las mutaciones puntuales, en las a-talasemias predominan las deleciones. Se describen mutaciones nóveles (cambios puntuales, deleciones y duplicaciones) que se presentan como eventos aislados con herencia recesiva o dominante. Es necesaria la interacción entre el médico hematólogo, el laboratorio bioquímico, el laboratorio molecular y el médico genetista, para llegar al diagnóstico certero de estos cuadros que permitirán reducir la incidencia de las formas severas.

Functional hemoglobin is a tetramer composed of 2 a and 2 non-a chains, encoded by genes that are organized in clusters and are expressed sequentially through development. There are multiple mutations described that affect these genes: if the sequence variant leads to a qualitative alteration, the resulting effect is a structural hemoglobinopathy, if it decreases the synthesis of the globin chains, thalassemia, and if it affects both the quality and quantity of the globin chain, the consequence is a thalassemic hemoglobinopathy. The aim of this paper is to present the molecular bases of hemoglobinopathies in Argentina, determined in 862 patients, based on the results of the molecular studies carried out in our laboratory from the analysis of 910 samples. Hb S is the most frequent structural hemoglobinopathy, ß-thalassemia mutations exhibit a pattern similar to the one displayed by Mediterranean basin populations, and a-thalassemia mutations are intrinsically related to the ancestry of those affected. These syndromes exhibit diverse molecular bases: structural hemoglobinopathies and ß-thalassemia are a consequence, mostly of point mutations, whereas in a-thalassemia deletions prevail. Novel mutations (point changes, deletions and duplications) that occurred as isolated events, with recessive or dominant inheritance, were described. Interaction between the hematologist, the geneticist and both the clinical and molecular biology laboratories is necessary to reach an accurate diagnosis of these syndromes and reduce the incidence of severe forms.

Durante o desenvolvimento de um indivíduo expressam-se diversas cadeias de globina de tipo a e não-a, que se combinam em tetrámeros para formar hemoglobina. Os genes que as codificam são organizados em famílias. Diferentes mutações afetam os genes que codificam as cadeias de globina: se provocarem alterações qualitativas originam quadros de hemoglobinopatias estruturais, se diminuírem as sínteses das cadeias de globina, talassemias, e se tiverem ambos os efeitos, hemoglobinopatias talassêmicas. O propósito deste trabalho é apresentar as bases moleculares das hemoglobinopatias na Argentina, num total de 862 amostras, com base nos estudos moleculares realizados neste laboratório a partir do estudo de 910 amostras de pacientes. No nosso meio, a Hb S é a hemoglobinopatia estrutural mais frequente, as ß-talassemias apresentam uma distribuição similar à bacia do Mediterrâneo e as a-talassemias estão intrinsecamente relacionadas com a ascendência dos afetados. As bases moleculares das hemoglobinopatias são variadas. Enquanto nas hemoglobinopatias estruturais e ß-talassemias predominam as mutações pontuais, nas a-talassemias predominam as deleções. Descrevem-se mutações incipientes (mudanças pontuais, deleções e duplicações) que se apresentam como eventos isolados com herança recessiva ou dominante. É necessária a interação entre o médico hematólogo, o laboratório bioquímico, o laboratório molecular e o médico geneticista, para chegar ao diagnóstico certo desses quadros que permitirão reduzir a incidência das formas severas.