Impact of Hydroxyurea to Treat Haematological Disorders on Male Fertility: Two Case Reports and a Systematic Review.

PURPOSE: Hydroxyurea (HU) is a cytoreductive agent used as standard treatment option for sickle cell anaemia/disease (SCD), essential thrombocythemia (ET), and polycythaemia vera (PV). Despite its overall good safety profile, its use also in relatively young patients raises an interest on its potential impact on spermatogenesis. To perform a systematic review of all published articles investigating fertility in male patients affected by SCD, ET, and PV and treated with HU. Two paradigmatic case reports of patients affected by PV and ET, respectively, have been also reported. MATERIALS AND METHODS: PubMed, EMBASE, and Cochrane databases were queried for all the published studies indexed up to November 15th, 2022. A combination of the following keywords was used: "hydroxyurea," "fertility," "male," "sperm," "sickle cell anaemia," "sickle cell disease," "essential thrombocythemia," "polycythaemia vera." RESULTS: Of 48 articles identified, 8 studies, involving 161 patients, were eligible for inclusion. Overall, the number of spermatogonia per round cross section of seminiferous tubule were decreased in patients with SCD compared to healthy males. HU treatment was always associated with a worsening of semen parameters, even up to azoospermia. Notably, treatment discontinuation was associated with an improvement of semen parameters and a trend toward normalization in the case of PV and ET, with a less clear amelioration in men with SCD. In both our patients with either PV or ET, HU discontinuation was associated with a significant improvement of spermatogenesis with successful spontaneous pregnancies. CONCLUSIONS: Published evidence do not consistently report normalization of spermatogenesis after HU discontinuation in SCD cases. Conversely, the literature almost consistently reported an improvement of semen parameters at the discontinuation of HU therapy in PV and ET cases. Our real-life two cases confirmed those findings. The willing of fatherhood and the need for effective fertility treatment warrant further research to improve work-up management in men with hematological disorders.

Dental caries in the permanent dentition and health-related quality of life among children and adolescents with sickle cell disease / Cáries dentárias na dentição permanente e qualidade de vida relacionada à saúde entre crianças e adolescentes com doença falciforme

Abstract The aim was to associate living, health and oral health conditions with the quality of life (QL) of children and adolescents (CA) with sickle cell disease (SCD). Of the 120 eligible users of a public hematological service, 106 CA with SCD from 6 to 18 years of age, and their caregivers, answered semi-structured questions about socio-demographic, health and oral health conditions. For QL, we used the validated instrument PedsQLSCD™. The oral clinical examination occurred according to the guidelines of WHO and SB Brazil 2010. The majority of CA were non-white people (88%), mean age of 10.4 (±2.9) years, family income of up to two monthly minimum wages, for 03 to 05 members, with diagnosis of sickle cell anemia by neonatal screening, hospitalizations were due allergic crises, polypharmacy and dental caries (51%) were present. "About the Impact of My Pain" was the best-fit model for the QLSCD (adjusted R²=56%; AIC=28.67; p=0.04). Dental caries in permanent dentition worsened the QLSCD (OR=0.53; IC95%=0.35-0.78; p<0.05) and was associated with the type of school, car ownership, number of family members, of complications and of the medications. To overcome this scenario, programmatic actions are required, and implementation of public policies specifically directed towards these groups.

Resumo Objetivou-se associar condições de vida, de saúde e de saúde bucal à qualidade de vida (QLV) de crianças e adolescentes (CA) com Doença Falciforme (DF). Dos 120 usuários elegíveis de um serviço público hematológico, 106 CA entre 6 e 18 anos de idade, e seus cuidadores, responderam questões semiestruturadas sobre condições sociodemográficas, de saúde e saúde bucal. Para a QLV, o instrumento validado PedsQL DF® foi aplicado. Na sequência, realizou-se o exame clínico bucal nas CA segundo diretrizes da OMS e do SB Brasil 2010. A maioria das CA era negra (88%), idade média de 10,4 (±2.9) anos, renda familiar de até dois salários mínimos, para 03 a 05 membros, diagnosticadas na triagem neonatal com anemia falciforme, internadas por crises álgicas, em uso de polifarmácia e com cárie dental (51%). O domínio "Sobre o Impacto da Minha Dor" foi preditivo da QLVDF (R² ajustado =56%; AIC=28.67; p=0,04). Nele, a cárie dental na dentição permanente piorou a QLVDF das CA (OR=0.53; IC95%=0.35-0.78; p<0,05), associando-se ao tipo de escola, posse de carro e do número de membros na família, de complicações da DF e de medicamentos. Os achados ratificam a dor como marca da DF e mostram a importância da saúde bucal na QLDF das CA. A implementação de políticas públicas específicas pode superar esse cenário.

The SickKids Caribbean Initiative to improve care for children with cancer and blood disorders.

To improve pediatric hematology and oncology outcomes, there is a recognized potential for partnerships between low- and high-resource institutions within health care systems. The SickKids Caribbean Initiative is a partnership between health care professionals at the Hospital for Sick Children in Toronto, Canada, and seven Caribbean institutions across six countries (Bahamas, Barbados, Jamaica, Saint Lucia, Saint Vincent and the Grenadines, and Trinidad and Tobago). The primary aim of the SickKids Caribbean Initiative has been to improve the outcomes and the quality of life of children in the Caribbean aged <18 years who have cancer and blood disorders. This article describes five key activities undertaken within the SickKids Caribbean Initiative, including providing education and training, assisting with case consultations and diagnostic services, developing local oncology databases, engaging in advocacy and ensuring stakeholder engagement, and coordinating administration and project management.

Las colaboraciones de instituciones de recursos bajos y altos dentro de los sistemas de atención de salud tienen un potencial reconocido para mejorar las respuestas a los tratamientos hematológicos y oncológicos pediátricos. La iniciativa SickKids para el Caribe es una asociación entre profesionales de la salud del Hospital for Sick Children de Toronto (Canadá) y siete instituciones de seis países del Caribe (Bahamas, Barbados, Jamaica, Santa Lucía, San Vicente y las Granadinas y Trinidad y Tabago). El objetivo principal de la iniciativa SickKids para el Caribe ha sido mejorar la respuesta a los tratamientos y la calidad de vida de los menores de 18 años del Caribe con cáncer o trastornos hematológicos. En este artículo se describen cinco actividades clave emprendidas en el marco de la iniciativa SickKids para el Caribe, consistentes en impartir formación y capacitación, prestar asistencia en materia de consultas de pacientes y servicios de diagnóstico, crear bases de datos locales en el área de la oncología, participar en actividades de promoción y garantizar la participación de las partes interesadas, y coordinar la administración y gestión de proyectos.

Há um potencial reconhecido para parcerias entre instituições com poucos e muitos recursos dentro dos sistemas de saúde para melhorar os resultados de hematologia e oncologia pediátricas. A iniciativa SickKids no Caribe é uma parceria entre profissionais de saúde do Hospital for Sick Children em Toronto, Canadá, e sete instituições em seis países do Caribe (Bahamas, Barbados, Jamaica, Santa Lúcia, São Vicente e Granadinas e Trinidad e Tobago). O objetivo principal da iniciativa SickKids no Caribe tem sido melhorar os desfechos e a qualidade de vida das crianças caribenhas com menos de 18 anos que têm câncer e doenças hematológicas. Este artigo descreve cinco atividades principais realizadas no âmbito da iniciativa SickKids no Caribe: oferecimento de educação e capacitação; assistência em consultas de casos e serviços diagnósticos; desenvolvimento de bancos de dados locais em oncologia; promoção da causa, assegurando o envolvimento das partes interessadas; e coordenação da administração e da gestão de projetos.

[Epidemiology of sickle cell disease in France and in the world]. / Épidémiologie de la drépanocytose en France et dans le monde.

EPIDEMIOLOGY OF SICKLE CELL DISEASE IN FRANCE AND IN THE WORLD. In a few decades, sickle cell disease has become the leading rare disease in France, with nearly 30,000 patients. It is the country in Europe where the most patients live. For historical reasons of immigration, half of these French patients live in the Paris area. The number of births of affected children increases every year, which explains the recurrent and increasing hospitalizations for vaso-occlusive crises, impacting the care system. Sub-Saharan African countries, along with India, are the countries most affected by the disease with an incidence of up to 1% of births. While infant mortality has become rare in industrialized countries, it is major in Africa where more than half of the children will not reach the age of 10.

ÉPIDÉMIOLOGIE DE LA DRÉPANOCYTOSE EN FRANCE ET DANS LE MONDE. En quelques dizaines d'années, la drépanocytose est devenue la première des maladies rares en France, avec près de 30 000 patients. C'est le pays d'Europe où vivent le plus de patients. Pour des raisons historiques d'immigration, la moitié de ces patients français vivent en Île-de-France. Le nombre de naissances d'enfants atteints augmente chaque année, ce qui explique des hospitalisations récurrentes et croissantes pour crises vaso-occlusives, impactant le système de soin mal préparé. Les pays d'Afrique subsaharienne sont, avec l'Inde, les pays les plus touchés par la maladie, avec une incidence allant jusqu'à 1 % des naissances. Alors que la mortalité infantile est devenue rare dans les pays industrialisés, elle est majeure en Afrique, où plus de la moitié des enfants n'atteindront pas l'âge de 10 ans.

[Management of acute complications of sickle cell disease]. / Prise en charge des complications aiguës de la drépanocytose.

MANAGEMENT OF ACUTE COMPLICATIONS OF SICKLE CELL DISEASE. Acute complications are the most frequent causes of hospitalization and morbidity in patients with sickle cell disease. Vaso-occlusive crisis are responsible of more than 90% of hospitalization, but numerous acute complications can affect multiples organ or function, that may be life-threatening. Thus, a single reason for hospitalization may include many complications such as worsening of an anemia, vascular disease (stroke, thrombosis, priapism), acute chest syndrome, liver or spleen sequestration. Evaluation of acute complications includes the understanding of chronic complications, particularities related to patient's age, the search for a triggering factor and a differential diagnosis. Analgesia and venous access difficulties, post transfusion immunization, medical history of the patient can make the management of acute complication particularly complex.

PRISE EN CHARGE DES COMPLICATIONS AIGUËS DE LA DRÉPANOCYTOSE. Les complications aiguës représentent la cause la plus fréquente de recours au système de soins et de morbi-mortalité des patients porteurs de drépanocytose. Quoique dominées par les crises vaso-occlusives osseuses qui constituent plus de 90 % des hospitalisations, les complications aiguës peuvent toucher de nombreux organes ou fonctions et menacer le pronostic vital du patient. Ainsi, un même motif d'hospitalisation peut être l'occasion d'une décompensation d'une anémie, d'une atteinte vasculaire (AVC, thrombose, priapisme), d'un syndrome thoracique aigu, d'une séquestration splénique ou hépatique. L'évaluation d'une complication aiguë doit prendre en compte l'histoire médicale du patient, les particularités liées à l'âge, la recherche d'un facteur déclenchant et d'un diagnostic différentiel. Les difficultés d'abord veineux, d'antalgie, les particularités transfusionnelles liées à la maladie et le parcours de soins de certains patients peuvent rendre la prise en charge particulièrement complexe.

[Disease modifying treatments for sickle cell disease]. / Traitement de fond et suivi de la drépanocytose.

DISEASE MODIFYING TREATMENTS FOR SICKLE CELL DISEASE. The two most widely available disease-modifying therapies, hydroxycarbamide and long-term redblood cells transfusions, are mostly introduced after the occurrence of complications. Hydroxycarbamide is mainly prescribed for the prevention of recurrent vaso-occlusive events (vaso-occlusive crisis and acute chest syndrome). Hydroxycarbamide efficacy and myelosuppressive effects are dependent on dose (usually 15 to 35 mg/kg/d) and patient compliance. Long-term transfusions are used for cerebral and end-organ damage protection or in second line after hydroxycarbamide for the prevention of recurrent vaso-occlusive events. The risks of each treatment should be weighed against the long-term risks and morbidity of the disease.

TRAITEMENT DE FOND ET SUIVI DE LA DRÉPANOCYTOSE. Le traitement de fond de la drépanocytose regroupe le traitement médicamenteux par hydroxycarbamide (HC), et les transfusions régulières de globules rouges, dits programmes transfusionnels, traitements atténuateurs de la maladie pour lesquels on dispose de données d'efficacité et de tolérance solides dans les formes génétiques sévères homozygotes SS et Sß°. Le traitement par HC, longtemps prescrit après la récurrence des complications, notamment vaso-occlusives (crises vaso-occlusives ou syndromes thoraciques aigus), est actuellement proposé plus précocement après la survenue des premières complications, voire en prévention des complications dès la petite enfance. L'efficacité du traitement par HC est étroitement liée à la dose (posologies habituelles utilisées entre 15 et 35 mg/kg/j) et à l'observance (une prise orale quotidienne). La posologie doit être adaptée à la tolérance hématologique (myélosuppression dose-dépendante). Le programme transfusionnel régulier reste indiqué, en première intention pour prévenir les complications cérébrales de la maladie, et en seconde ligne après l'HC pour prévenir la récurrence des complications vasoocclusives. La balance bénéfices-risques de chaque traitement doit être évaluée en regard de la morbidité de la maladie drépanocytaire.

[Therapeutic approaches in sickle cell disease]. / Perspectives thérapeutiques dans la drépanocytose.

THERAPEUTIC APPROACHES IN SICKLE CELL DISEASE. Sickle cell disease, the most common genetic disease in France, is still burdened with morbidity and early mortality before the age of 50. When the first-line treatment, hydroxyurea, is insufficient or in the case of organic damage(s) (in particular cerebral vasculopathy), a therapeutic intensification must be considered. New molecules are now available, such as voxelotor and crizanlizumab, but only hematopoietic stem cell (HSC) transplantation can cure the disease. Allogeneic HSC transplantation during childhood with a sibling donor is the reference but it is now possible to perform this procedure in adults with a reduced pre-transplant conditioning. Gene therapy, which consists of an autograft of genetically modified HSCs, has obtained promising results but has not yet demonstrated a complete cure of the disease (protocols underway). The toxicity of myeloablative conditioning (used in pediatrics or for gene therapy), particularly the sterility induced, and the risk of graft-versushost disease (for allogeneic transplantation) are limiting factors of these treatments.

PERSPECTIVES THÉRAPEUTIQUES DANS LA DRÉPANOCYTOSE. La drépanocytose, maladie génétique la plus fréquente en France, reste grevée d'une morbidité et d'une mortalité précoce avant l'âge de 50 ans. Dans le cas où le traitement de première ligne, l'hydroxyurée, est insuffisant ou en cas d'atteinte(s) organique(s) (en particulier la vasculopathie cérébrale), une intensification thérapeutique doit être envisagée. De nouvelles molécules sont aujourd'hui disponibles comme le voxelotor et le crizanlizumab, mais seule la greffe de cellules souches hématopoïétiques (CSH) permet une guérison de la maladie. L'allogreffe de CSH pendant l'enfance avec un donneur compatible intrafamilial (géno-identique) est la référence, mais il est désormais possible de réaliser cette procédure chez les adultes avec un conditionnement prégreffe d'intensité réduite. La thérapie génique qui consiste en une autogreffe de CSH génétiquement modifiées a obtenu des résultats prometteurs mais n'a pas démontré à ce jour une guérison complète de la maladie (protocoles en cours). La toxicité des conditionnements dits myéloablatifs (utilisés en âge pédiatrique ou pour la thérapie génique), notamment la stérilité induite, le risque de réaction du greffon contre l'hôte (pour la greffe allogénique), sont des facteurs limitants de ces traitements.

Mortality Rates and autopsy findings in fat embolism syndrome complicating sickle cell disease.

Fat embolism syndrome is a rare but underdiagnosed complication of sickle cell disease associated with high morbidity and mortality. It affects predominantly patients with a previously mild course of their illness and those of non-SS genotypes while there is possibly an association with infection with human parvovirus B19 (HPV B19). Here, we present the mortality rates and autopsy findings of all reported cases to date. A systematic review has revealed 99 published cases in the world literature with a mortality rate of 46%. Mortality varied greatly according to the time of reported cases with no survivors in the 1940s, 1950s or 1960s and no deaths since 2020. 35% of cases had previously undiagnosed sickle cell disease and the latter was only identified at autopsy after developing fat embolism with a fatal outcome. 20% of cases reported after 1986 tested positive for HPV B19 with an associated mortality of 63% whereas in cases that have not documented HPV B19 infection the mortality was 32%. The organs most often staining positive for fat were the kidneys, lungs, brain and heart whereas ectopic haematopoietic tissue was found in 45% of the examined lung specimens.

The SickKids Caribbean Initiative to improve care for children with cancer and blood disorders / La iniciativa SickKids para el Caribe para mejorar la atención a pacientes pediátricos con cáncer o trastornos hematológicos / Iniciativa SickKids no Caribe: melhorar o atendimento a crianças com câncer e doenças hematológicas

ABSTRACT To improve pediatric hematology and oncology outcomes, there is a recognized potential for partnerships between low- and high-resource institutions within health care systems. The SickKids Caribbean Initiative is a partnership between health care professionals at the Hospital for Sick Children in Toronto, Canada, and seven Caribbean institutions across six countries (Bahamas, Barbados, Jamaica, Saint Lucia, Saint Vincent and the Grenadines, and Trinidad and Tobago). The primary aim of the SickKids Caribbean Initiative has been to improve the outcomes and the quality of life of children in the Caribbean aged <18 years who have cancer and blood disorders. This article describes five key activities undertaken within the SickKids Caribbean Initiative, including providing education and training, assisting with case consultations and diagnostic services, developing local oncology databases, engaging in advocacy and ensuring stakeholder engagement, and coordinating administration and project management.

RESUMEN Las colaboraciones de instituciones de recursos bajos y altos dentro de los sistemas de atención de salud tienen un potencial reconocido para mejorar las respuestas a los tratamientos hematológicos y oncológicos pediátricos. La iniciativa SickKids para el Caribe es una asociación entre profesionales de la salud del Hospital for Sick Children de Toronto (Canadá) y siete instituciones de seis países del Caribe (Bahamas, Barbados, Jamaica, Santa Lucía, San Vicente y las Granadinas y Trinidad y Tabago). El objetivo principal de la iniciativa SickKids para el Caribe ha sido mejorar la respuesta a los tratamientos y la calidad de vida de los menores de 18 años del Caribe con cáncer o trastornos hematológicos. En este artículo se describen cinco actividades clave emprendidas en el marco de la iniciativa SickKids para el Caribe, consistentes en impartir formación y capacitación, prestar asistencia en materia de consultas de pacientes y servicios de diagnóstico, crear bases de datos locales en el área de la oncología, participar en actividades de promoción y garantizar la participación de las partes interesadas, y coordinar la administración y gestión de proyectos.

RESUMO Há um potencial reconhecido para parcerias entre instituições com poucos e muitos recursos dentro dos sistemas de saúde para melhorar os resultados de hematologia e oncologia pediátricas. A iniciativa SickKids no Caribe é uma parceria entre profissionais de saúde do Hospital for Sick Children em Toronto, Canadá, e sete instituições em seis países do Caribe (Bahamas, Barbados, Jamaica, Santa Lúcia, São Vicente e Granadinas e Trinidad e Tobago). O objetivo principal da iniciativa SickKids no Caribe tem sido melhorar os desfechos e a qualidade de vida das crianças caribenhas com menos de 18 anos que têm câncer e doenças hematológicas. Este artigo descreve cinco atividades principais realizadas no âmbito da iniciativa SickKids no Caribe: oferecimento de educação e capacitação; assistência em consultas de casos e serviços diagnósticos; desenvolvimento de bancos de dados locais em oncologia; promoção da causa, assegurando o envolvimento das partes interessadas; e coordenação da administração e da gestão de projetos.

Association Between Lipid Profile and Clinical Manifestations in Sickle Cell Anemia: A Systematic Review

Abstract Introduction Sickle cell anemia (SCA) is a genetic disease associated with frequent episodes of acute illness. Changes in the lipid profile and a chronic inflammatory process make up the molecular aspects observed in this disease. Associations between these mechanisms and clinical manifestations could thus define severity profiles and therapeutic strategies. Objectives To verify whether there is an association between lipid profile and clinical manifestations in patients with SCA and if there is a correlation between lipid profile and laboratory markers in this disease. Methodology According to the PRISMA guidelines, a systematic review of the literature was conducted by searching the MEDLINE/PubMed, LILACS, SciELO, Scopus, and Cochrane databases. Articles were screened by reading the titles and abstracts, reaching those selected for full-text reading. The included studies were published between 2010 and 2020, were fully available in the databases, and addressed the proposed theme. The risk of individual bias was assessed by using the Joanna Briggs Institute checklist and the Newcastle-Ottawa scale. Results Out of the 144 identified articles, 15 were selected for analysis, resulting in a sample size of 2,230 individuals. HDL-C, LDL-C, total cholesterol , and triglycerides were the main variables analyzed in the lipid profiles. A correlation was observed between these variables and some of the most relevant clinical events in the disease, including vaso-occlusive seizures and acute thoracic syndrome. Conclusion Lipid metabolism disorders, especially hypocholesterolemia and hypertriglyceridemia, are linked to clinical events observed in SCA, suggesting they play a relevant role in the multifactorial pathogenesis of this disease.

Fatores preditivos para a cicatrização de úlceras da perna em pessoas com doença falciforme: coorte retrospectivo / Factors predictive of leg ulcer healing in people with sickle cell disease: a retrospective cohort / Factores predictivos de la cicatrización de úlceras de la pierna en personas con anemia falciforme: cohorte retrospectivo

Objetivo: identificar a taxa de cicatrização e os fatores preditivos para cura das úlceras da perna em pessoas com doença falciforme. Método: coorte retrospectivo, realizado de junho a agosto de 2020, em um serviço especializado de tratamento de pessoas com feridas, contemplando um período de nove anos, com amostra de 52 úlceras que atenderam os critérios de elegibilidade. Protocolo de pesquisa aprovado pelo comitê de ética. Resultados: a taxa de cicatrização foi 76,9%. Os fatores que contribuíram para cura em um menor tempo foram a não recidiva (HR= 3,03; IC 95%: 1,07-8,60) e extensão abaixo da mediana 7,25 cm2 (HR= 2,25; IC 95%: 1,19-4,27). Fatores para a não cicatrização foram: coberturas de alginato de cálcio (HR=0,29; IC 95%: 0,13-0,62), carvão com prata (HR=0,06; IC 95%: 0,02-0,21) e outras (HR=0,35; IC 95%: 0,15-0,80). Conclusão: a taxa de cicatrização da úlcera foi elevada. Recidiva, área da úlcera e determinadas coberturas podem influenciar no processo de cura.

Objective: to identify the healing rate and predictive factors for healing of leg ulcers in people with sickle cell disease. Method: retrospective cohort, carried out from June to August 2020, in a specialized service for the treatment of people with wounds, covering a period of nine years, with a sample of 52 ulcers that met the eligibility criteria. Research protocol approved by the ethics committee. Results: healing rate was 76.9%. The factors that contributed to cure in a shorter time were non-recurrence (HR= 3.03; 95% CI: 1.07-8.60) and extension below the median 7.25 cm2 (HR= 2.25; CI 95%: 1.19-4.27). Factors for non-healing were: calcium alginate dressings (HR=0.29; 95% CI: 0.13-0.62), charcoal with silver (HR=0.06; 95% CI: 0.02- 0.21) and others (HR=0.35; 95% CI: 0.15-0.80). Conclusion: the ulcer healing rate was high. Recurrence, ulcer area and certain dressings can influence the healing process.

Objetivo: identificar la tasa de curación y los factores predictivos para la curación de las úlceras en las piernas en pacientes con enfermedad de células falciformes. Método: cohorte retrospectiva, realizada de junio a agosto de 2020, en un servicio especializado para el tratamiento de personas con heridas, cubriendo un período de nueve años, con una muestra de 52 úlceras que cumplieron con los criterios de elegibilidad. Protocolo de investigación aprobado por el comité de ética. Resultados: La tasa de cicatrización fue del 76,9%. Los factores que contribuyeron a la curación en menor tiempo fueron la no recurrencia (HR= 3,03; IC 95%: 1,07-8,60) y extensión por debajo de la mediana de 7,25 cm2 (HR= 2,25; IC 95%: 1,19-4,27). Los factores de no cicatrización fueron: apósitos de alginato de calcio (HR=0,29; IC 95%: 0,13-0,62), carbón con plata (HR=0,06; IC 95%: 0,02-0,21) y otros (HR=0,35; IC 95%: 0,15-0,80). Conclusión: la tasa de curación de la úlcera fue alta. La recurrencia, el área de la úlcera y ciertos revestimientos pueden influir en el proceso de curación.

Prevalência das Complicações Cardiovasculares nos Indivíduos com Anemia Falciforme e Outras Hemoglobinopatias: Uma Revisão Sistemática / Prevalence of Cardiovascular Complications in Individuals with Sickle Cell Anemia and Other Hemoglobinopathies: A Systematic Review

Resumo Fundamento A anemia falciforme (AF) é uma doença hereditária cujas complicações cardiovasculares são a principal causa de morte, o mesmo sendo observado em outras hemoglobinopatias. A identificação precoce dessas alterações pode modificar favoravelmente o curso da doença. Objetivo Comparar a prevalência de complicações cardiovasculares entre indivíduos com AF e indivíduos com outras hemoglobinopatias. Métodos Seguindo recomendações do protocolo PRISMA, realizou-se revisão sistemática da literatura com buscas nas bases de dados PubMed/Medline, associadas à busca manual. Incluídos estudos que analisaram a prevalência das alterações cardiovasculares nas hemoglobinopatias (AF, traço falciforme, hemoglobinopatia SC, alfatalassemia e betatalassemia). A qualidade metodológica dos artigos foi realizada pela escala de Newcastle-Ottawa. Resultados Foram selecionados para análise quatro estudos, resultando em um tamanho amostral de 582 participantes: 289 portadores de AF, 133 possuem hemoglobinopatia SC, 40 com betatalassemia, 100 indivíduos saudáveis e nenhum com alfatalassemia ou traço falcêmico. Dilatação das câmaras cardíacas, hipertrofia ventricular esquerda e direita, hipertensão pulmonar, disfunção diastólica, insuficiência mitral e insuficiência tricúspide são mais prevalentes na AF do que nas demais hemoglobinopatias consideradas. A sobrecarga miocárdica de ferro é mais frequente na talassemia maior do que na AF. A função sistólica foi similar entre as hemoglobinopatias. Conclusão Verificou-se maior comprometimento cardiovascular nos indivíduos com AF do que naqueles com as demais hemoglobinopatias, reforçando a necessidade de acompanhamento cardiovascular regular e frequente nos pacientes falcêmicos.

Abstract Background Sickle cell anemia (SCA) is a hereditary disease whose cardiovascular complications are the main cause of death, the same being observed in other hemoglobinopathies. Early identification of these changes can favorably modify the course of the disease. Objective To compare the prevalence of cardiovascular complications between individuals with SCA and individuals with other hemoglobinopathies. Method Following the recommendations of the PRISMA protocol, a systematic literature review was carried out with searches in PubMed/Medline databases, associated with a manual search. Studies that analyzed the prevalence of cardiovascular alterations in hemoglobinopathies (SCA, sickle cell trait, SC hemoglobinopathy, alpha-thalassemia and beta-thalassemia) were included. The methodological quality of the articles was assessed using the Newcastle-Ottawa scale. Results Four studies were selected for analysis, resulting in a sample size of 582 participants: 289 with SCA, 133 with SC hemoglobinopathy, 40 with beta-thalassemia, 100 healthy individuals and none with alpha-thalassemia or sickle cell trait. Dilatation of the cardiac chambers, left and right ventricular hypertrophy, pulmonary hypertension, diastolic dysfunction, mitral regurgitation and tricuspid regurgitation are more prevalent in SCA than in the other hemoglobinopathies considered. Myocardial iron overload is more frequent in thalassemia major than in sickle cell anemia. Systolic function is similar between different hemoglobinopathies. Conclusion There is greater cardiovascular impairment in individuals with SCA than in those with other hemoglobinopathies, reinforcing the necessity for regular cardiovascular follow-up in sickle cell patients.