Sickle cell anemia: hierarchical cluster analysis and clinical profile in a cohort in Brazil

Abstract Introduction Sickle cell anemia is a monogenic disorder caused by a mutation in the β-hemoglobin gene, resulting in sickle hemoglobin that can polymerize. Presentation and clinical course have significant inter-individual variability and classifying these patients for severity is a challenge. Methods We applied hierarchical clusters with 10 routine laboratory tests to understand if this grouping could be associated with clinical manifestations. We included 145 adult homozygous patients (SS) at an outpatient clinic in a retrospective study. Results We found five clusters by counting those that had been differentiated by unconjugated bilirubin, reticulocytes, LDH, leukocytes, lymphocytes and monocytes. When comparing groups to clinical findings, the clusters were different only for liver abnormality. Cluster 3 had the lower median of reticulocytes, LDH, leukocytes, lymphocytes and monocytes and a higher percentage of patients under treatment. Clusters 4 and 5 had higher frequencies of liver impairment and higher medians of reticulocytes, LDH, leukocytes, lymphocytes and monocytes. Hemolysis and inflammation seemed to influence the grouping. Conclusion In our study, cluster analysis showed five groups that exhibited different degrees of inflammation and hemolysis. When comparing clinical data, the result was different only for the criteria of liver abnormality.

IRF4 and IRF8 expression are associated with clinical phenotype and clinico-hematological response to hydroxyurea in essential thrombocythemia / 医学前沿

The morbidity and mortality of myeloproliferative neoplasms (MPNs) are primarily caused by arterial and venous complications, progression to myelofibrosis, and transformation to acute leukemia. However, identifying molecular-based biomarkers for risk stratification of patients with MPNs remains a challenge. We have previously shown that interferon regulatory factor-8 (IRF8) and IRF4 serve as tumor suppressors in myeloid cells. In this study, we evaluated the expression of IRF4 and IRF8 and the JAK2V617F mutant allele burden in patients with MPNs. Patients with decreased IRF4 expression were correlated with a more developed MPN phenotype in myelofibrosis (MF) and secondary AML (sAML) transformed from MPNs versus essential thrombocythemia (ET). Negative correlations between the JAK2V617F allele burden and the expression of IRF8 (P < 0.05) and IRF4 (P < 0.001) and between white blood cell (WBC) count and IRF4 expression (P < 0.05) were found in ET patients. IRF8 expression was negatively correlated with the JAK2V617F allele burden (P < 0.05) in polycythemia vera patients. Complete response (CR), partial response (PR), and no response (NR) were observed in 67.5%,10%, and 22.5% of ET patients treated with hydroxyurea (HU), respectively, in 12 months. At 3 months, patients in the CR group showed high IRF4 and IRF8 expression compared with patients in the PR and NR groups. In the 12-month therapy period, low IRF4 and IRF8 expression were independently associated with the unfavorable response to HU and high WBC count. Our data indicate that the expression of IRF4 and IRF8 was associated with the MPN phenotype, which may serve as biomarkers for the response to HU in ET.

Anemia falciforme: una revisión sobre el genotipo de la enfermedad, haplotipos, diagnóstico y estudios asociados / Disease genotype, haplotypes, diagnosis and associated studies in sickle cell anemia

Sickle cell anemia is a type of hemoglobinopathy characterized by a specific mutation in the beta globin gene with the consequent generation of an unstable hemoglobin that crystallizes in a state of hypoxia. This causes a change in the structure of the red blood cell, which ends up producing vaso-occlusion with the corresponding clinical complications for the patient. Worldwide, various diagnostic tests have been developed that allow the appropriate approach to the affected patient. These include techniques for the determination of hemoglobin and the use of molecular markers, among others. There are new therapeutic alternatives to the use of hydroxyurea and L-glutamine, such as the use of gene therapy tools. The most recent experimental trials are exploring gene editing techniques.

Droga antimetabolítica en pacientes con enfermedad de células falciformes en el centro hematológico del hospital de capacitación de Kerbalaa / Antimetabolite drug in patients with sickle cell diseases in hematological center of Kerbalaa training hospital

Antecedentes: el fármaco antimetabolito aumenta el nivel de hemoglobina fetal y reduce la frecuencia de crisis en pacientes con anemia de células falciformes. Objetivo: Evaluar el efecto de los antimetabolitos (hidroxiurea) en casos con crisis falciforme frecuente de anemia de células falciformes y talasemia no dependiente de transfusiones en el hospital de formación de Karbala desde abril de 2016 hasta diciembre de 2020. Pacientes y métodos: de 81 pacientes realizados en este estudio de casos y controles, cuarenta recibieron hidroxiurea y los otros cuarenta y un pacientes no. Se realizaron monitoreos cada dos semanas en los primeros tres meses mediante el envío para análisis (Hb, WBC, recuento de plaquetas y urea en sangre y creatinina sérica) LA PRENSA MÉDICA ARGENTINA Antimetabolite drug in patients with sickle cell diseases in hematological center of kerbalaa training hospital 161 V.107/Nº 3 además de la evaluación de los efectos secundarios de los medicamentos. Los cuarenta y un pacientes restantes que rechazaron la terapia con medicamentos los consideramos un grupo de control. Resultado: el grupo de casos que recibió hidroxilurea tuvo crisis principalmente después de 12 semanas desde la última crisis, mientras que el grupo de control tuvo crisis principalmente cada 3 a 7 semanas con un valor P=0,0001. No hubo efectos secundarios en el 77,5% de los casos que recibieron hidroxiurea. El 22,5% restante de los casos tuvo efectos secundarios menores o inespecíficos. Conclusión: En pacientes con drepanocitosis que sufrieron episodios recurrentes de crisis, la terapia con Hidroxiurea disminuye significativamente la frecuencia de la crisis dolorosa, con un bajo nivel de efectos secundarios en comparación con el grupo control.

Background: the antimetabolite drug increase fetal hemoglobin level and reduce the frequency of crisis in sickle cell disease patients. Aim: To evaluate the effect of antimetabolites (hydroxyurea) in cases with frequent sickling crisis of sickle cell disease and non-transfusion dependent thalassemia in Karbala training hospital from APRIL 2016 till December 2020. Patient and methods: from eighty-one patients conducted in this case control study, forty were received hydroxyurea and the other forty-one patients were not. Monitoring every two weeks in the first three months by sending for investigations (Hb, WBC, platelet count and blood urea and serum creatinine) in addition to assessment of drug side effects. The remaining forty-one patients who refused drug therapy we consider them as a control group. Result: the case group who received hydroxylurea had crisis mostly after 12 weeks from last crisis, whereas the control group had crisis mostly each 3 to 7 weeks in P value 0.0001. There was no side effect in 77.5% of cases received hydroxyurea.The remaining 22.5% of cases had less or nonspecific side effects. Conclusion: In patient with sickle cell diseases who suffered from recurrent episodes of crisis, Hydroxyurea therapy significantly decreases the frequency of the painful crisis, with low level of side effects in comparison with control group

Estudos econômicos completos sobre tratamentos da anemia falciforme / Estudios económicos completos sobre tratamientos para la anemia falciforme / Comprehensive economic studies on sickle cell anemia treatments

Resumo Objetivo: Analisar os estudos econômicos completos com enfoque nos tratamentos da Anemia Falciforme. Métodos: Estudo de revisão integrativa de literatura desenvolvido mediante coleta de dados nas bases eletrônicas National Library of Medicine - Medline via PubMed; Elservier's Scopus; Current Index to Nursing and Allied Health Literature; Science Direct e Web of Science com descritores indexados no Medical Subject Headings. Os estudos foram selecionados pelo teste de relevância e analisados de acordo com a classificação das análises econômicas em saúde e o sistema de Classificação da qualidade das evidências e a força das recomendações. Resultados: Fizeram parte desta revisão 09 artigos, dos quais sete recuperados na base Elservier's Scopus e dois na Medline via PubMed. Todos estudos completos com enfoque nas perspectivas do uso da Hidroxiureia e da transfusão sanguínea no tratamento da Anemia Falciforme. Conclusão: Não foram identificados estudos realizados no Brasil com este tipo de análise para Anemia Falciforme. Há muito a ser feito mundialmente para avaliação das tecnologias vigentes, reavaliação das utilizadas atualmente e implementação de diagnóstico e tratamento contínuo, com um sistema que garanta uma rede de atenção ativa e eficiente aos pacientes.

Resumen Objetivo: Analizar los estudios económicos completos con enfoque en tratamientos para la anemia falciforme Métodos: Estudio de revisión integradora de la literatura desarrollado mediante la recolección de datos en las bases electrónicas National Library of Medicine - Medline vía PubMed; Elservier's Scopus; Current Index to Nursing and Allied Health Literature; Science Direct y Web of Science con descriptores indexados en Medical Subject Headings. Los estudios fueron seleccionados mediante la prueba de relevancia y analizados de acuerdo con la clasificación de análisis económicos en salud y con el sistema de clasificación de la calidad de las evidencias y la fuerza de las recomendaciones. Resultados: Nueve artículos formaron parte de esta revisión, de los cuales siete fueron encontrados en la base Elservier's Scopus y dos en Medline vía PubMed. Todos son estudios completos con enfoque en las perspectivas del uso de hidroxiurea y transfusión sanguínea para el tratamiento de anemia falciforme. Conclusión: No se identificaron estudios realizados en Brasil con este tipo de análisis de anemia falciforme. Hay mucho por hacer a nivel mundial para evaluar las tecnologías vigentes, revaluar las que se utilizan en la actualidad e implementar el diagnóstico y tratamiento continuo, con un sistema que garantice una red de atención activa y eficiente para los pacientes.

Abstract Objective: To analyze complete economic studies focusing on sickle cell anemia treatments. Methods: Integrative literature review developed by collecting data in the electronic databases National Library of Medicine - Medline via PubMed; Elsevier's Scopus; Current Index to Nursing and Allied Health Literature; Science Direct and Web of Science with descriptors indexed in Medical Subject Headings. The studies were selected by the relevance test and analyzed according to the classification of economic analyses in health and the classification system of evidence quality and strength of recommendations. Results: Nine articles were part of this review, seven of which were retrieved from Elsevier's Scopus and two from Medline via PubMed. All articles reported on studies focusing on the perspectives of using hydroxyurea and blood transfusion in the treatment of sickle cell anemia. Conclusion: No studies were identified that were conducted in Brazil and involved this type of analysis for sickle cell anemia. Much remains to be done worldwide to assess existing technologies, reassess the technologies currently used and implement continuous diagnosis and treatment, by means of a system that guarantees an active and efficient care network for the patients.

Internalização do cuidado: um estudo qualitativo com escolares que convivem com a doença falciforme / Internalizacion del cuidado: un estudio cualitativo com niños que viven con enfermedad de células falciformes / Internalization of care: a qualitative study with schoolchildren living with sickle cell disease

RESUMO Objetivo analisar a internalização do cuidado com o corpo pelo escolar com a doença falciforme com base na teoria do desenvolvimento de Vigotski e no conceito de cuidado de Collière. Método Estudo qualitativo com 15 escolares que convivem com a doença falciforme, acompanhados em ambulatório na cidade de Vitoria - ES. A técnica utilizada foi a entrevista individual e a análise temática. A hidratação corporal, o brincar, a prevenção e manejo da crise falcêmica, a alimentação e as roupas foram as unidades temáticas que emergiram. Resultados Os participantes referiram ingerir variados tipos de líquidos. As brincadeiras foram predominantemente ativas. Os medicamentos foram de reparação e manutenção da saúde. Não se evidenciou consumo de alimentos saudáveis. Observou-se a utilização de roupas adequadas ao frio. A dor foi um signo da internalização do cuidado e do conhecimento para brincadeiras. A diminuição de líquidos e roupas inadequadas desencadearam a crise falcêmica. Considerações Finais Evidenciaram-se a internalização do conhecimento e dos cuidados mediados pela dor e o despreparo dos professores pela falta de conhecimento. Implicações para a prática este estudo poderá subsidiar a melhor articulação entre profissional de saúde, criança e escola.

RESUMEN Objetivo analizar la internalización de la atención por parte del escolar con la enfermedad de células falciformes basado en la teoría del desarrollo de Vigotski y el concepto de atención de Collière. Método Estudio cualitativo con 15 escolares que viven con la enfermedad de células falciformes, monitoreados en una clínica ambulatoria en la ciudad de Vitoria - ES. La técnica fue la entrevista individual y el análisis temático. La hidratación corporal, el juego, la prevención y el manejo de la crisis falcémica, la alimentación y la ropa fueron las unidades temáticas que emergieron. Resultados Los participantes informaron de la ingestión de varios tipos de líquidos. Los juegos fueron predominantemente activos. Los medicamentos fueron de reparación y mantenimiento de la salud. No se ha demostrado el consumo de alimentos saludables. Se observó el uso de ropa adecuada para el frío. El dolor fue un signo de la internalización de la atención y el conocimiento para los juegos. La disminución de líquidos y la ropa inadecuada desencadenaron la crisis falcémica. Consideraciones finales Se señalaron la internalización del conocimiento y la atención mediados por el dolor y la falta de preparación de los maestros debido a la falta de conocimiento. Implicaciones para la práctica este estudio podrá subsidiar la mejor articulación entre los profesionales de la salud, los niños y la escuela.

ABSTRACT Objective to analyze the internalization of body care by the schoolchildren with sickle cell disease based on Vigotski's development theory and Collière's concept of care. Method Qualitative study with 15 schoolchildren living with sickle cell disease, followed in an outpatient clinic in the city of Vitoria - ES. The technique was the individual interview and thematic analysis. Body hydration, playing, prevention and management of the sickle cell crisis, food and clothing were the thematic units that emerged. Results Participants reported ingesting various types of liquids. The games were predominantly active. The medications were repair and maintenance of health. It was observed no consumption of healthy foods. The use of clothes suitable for the cold was evidenced. Pain was a sign of the internalization of care and knowledge for games. The decrease in liquids and inadequate clothing triggered the sickle cell crisis. Final Considerations The internalization of knowledge and care mediated by pain and the unpreparedness of teachers due to lack of knowledge were highlighted. Implications for practice this study can support the best articulation between health professionals, children and school.

Occurrence of unusual haemoglobinopathies in balochistan: hb sd and hb se - presentation with osteomyelitis / Ocorrência de hemoglobinopatias incomuns no baluchistão: hb sd e hb se - apresentação com osteomielite

ABSTRACT Objective: To describe two cases of unusual variants of sickle cell disease. Case description: We present two cases of sickle cell disease variants (haemoglobinopathies), from unrelated families, in the state of Balochistan (Pakistan). One was diagnosed with sickle cell disease in the haemoglobin electrophoresis, whereas the other was diagnosed with sickle cell SE disease. Both were diagnosed based on the presentation of osteomyelitis. Comments: Haemoglobin SD disease (Hb SD) and haemoglobin SE disease (Hb SE) are rare haemoglobinopathies in the world. The lack of available literature suggests that both are variants of sickle cell disease (SCD), with heterogeneous nature. The prevalence of sickle cell disease with compound heterozygotes was found at a variable frequency in the population of the Asian Southeast. The frequency of osteomyelitis in SCD is 12 to 18%, but its occurrence among variant haemoglobinopathies is little reported. Both reported cases presented with osteomyelitis as a characteristic of the disease presentation.

RESUMO Objetivo: Descrever dois casos de variantes raras da hemoglobinopatia falciforme. Descrição do caso: Apresentamos aqui dois casos de hemoglobinopatias variantes das células falciformes, de famílias não relacionadas, no estado do Baluchistão (Paquistão), sendo um diagnosticado como doença da hemoglobina SD na eletroforese de hemoglobina, enquanto o outro com doença da hemoglobina SE. Ambos foram diagnosticados a partir da apresentação de osteomielite. Comentários: Hemoglobina SD (Hb SD) e hemoglobina SE (Hb SE) são hemoglobinopatias raras no mundo. A escassez de literatura disponível sugere que ambas são variantes da doença falciforme (DF) com natureza heterogênea. A prevalência de hemoglobinopatia falciforme com heterozigosidade composta foi encontrada com frequência variável na população do sudeste asiático. A frequência de osteomielite na DF é de 12 a 18%, mas sua ocorrência entre as hemoglobinopatias falciformes variantes é pouco relatada. Os dois casos reportados apresentaram osteomielite como característica de apresentação da doença.

Aspectos clínicos, laboratoriais e tratamento da leucemia mieloide crônica em cão: relato de caso / Clinical aspects, hematological changes and treatments of chronic myeloid leukemia in dog: case report

O objetivo deste relato é apresentar o caso clínico de uma cadela, sem raça definida, com cinco anos de idade, diagnosticada com leucemia mieloide crônica (LMC). As leucemias são neoplasias malignas que se originam de células precursoras da medula óssea e as consequências podem ser trombocitopenia, anemia, leucocitose persistente e presença de células neoplásicas no sangue. O tratamento de escolha envolve o uso de inibidores de tirosina quinase, porém este não pode ser usado neste caso. Dessa forma a cadela recebeu diferentes protocolos quimioterápicos que incluíram inicialmente hidroxiureia, citarabina, doxorrubicina e prednisona. Devido a remissão parcial dos sinais clínicos e a resposta terapêutica pouco duradoura a essas medicações o protocolo foi alterado para quimioterapia metronômica com clorambucil. O uso desses quimioterápicos não foram eficazes em reduzir a leucocitose e controlar a anemia e trombocitopenia da paciente, devido a ocorrência do surgimento de células imaturas no sangue e resistência aos quimioterápicos. Na ausência da crise e da possibilidade do uso dos inibidores de tirosina quinase, a hidroxiureia permanece sendo o quimioterápico de eleição. O animal apresentou sobrevida de 210 dias, devido a leucocitose e anemia severas pouco responsivas ao protocolo terapêutico utilizado e o surgimento no hemograma de precursores neutrofilicos que ocorreu 46 dias após ao início do tratamento com hidroxiureia.

The aim of this report is to present the clinical case of a five-year-old mixed breed female dog diagnosed with chronic myeloid leukemia (CML). Leukemias are malignant neoplasms that originate from bone marrow precursor cells and the consequences can be thrombocytopenia, anemia, persistent leukocytosis and the presence of neoplastic cells in the blood. The treatment of choice involves the use of tyrosine kinase inhibitors, but it cannot be used in this case. Thus, the dog received different chemotherapy protocols that initially included hydroxyurea, cytarabine, doxorubicin and prednisone. Due to the partial remission of clinical signs and the short-term therapeutic response to these medications, the protocol was changed to metronomic chemotherapy with chlorambucil. The use of these chemotherapeutic agents was not effective in reducing leukocytosis and controlling the patient's anemia and thrombocytopenia, due to the occurrence of immature cells in the blood and resistance to chemotherapeutic agents. In the absence of the crisis and the possibility of using tyrosine kinase inhibitors, hydroxyurea remains the chemotherapy of choice. The animal had a 210-day survival, due to severe leukocytosis and anemia, which were not responsive to the therapeutic protocol used and the appearance in the blood count of neutrophilic precursors that occurred 46 days after the beginning of hydroxyurea treatment.

Informe diário de evidências COVID-19: busca realizada em 30 de junho de 2020 / COVID-19 daily evidence report: search conducted on June 30, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos e 31 protocolos.

Síntese de evidências para políticas de saúde: prevenindo as complicações da doença falciforme / Evidence health policy brief: preventing the complications of sickle cell disease

Essa síntese teve como objetivo levantar opções para prevenção de complicações da doença falciforme, e informar sobre avanços na implementação da política no país. Seguem as opções descritas na síntese que já fazem parte das recomendações do Ministério da Saúde: Promover a antibioticoterapia profilática e a vacinação anti-pneumocócica; Promover o uso de hidroxiureia para prevenção e tratamento de complicações da doença falciforme; Promover o uso de ultrassonografia Doppler Transcraniano (DTC) e transfusão sanguínea para a prevenção primária de acidente vascular cerebral (AVC); Promover a educação em saúde para as pessoas com doença falciforme e seus cuidadores sobre medidas para reduzir as complicações

Effects of oxidative stress on liver, brain and spinal cord of rats using L-NAME and treated with hydroxyurea. A model of sickle cell complication

Abstract Purpose: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. Methods: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. Results: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. Conclusions: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.

The Effect of Hydroxyurea Therapy on Adverse Clinical Events and Haematological Indices in Paediatric Patients with Sickle Cell Anaemia / Efecto de la Terapia con Hidroxiurea en los Eventos Clínicos Adversos y los Indices Haematológicos de Pacientes Paediátricos con Aanemia de Células Falciformes

ABSTRACT Objective: The aim of this study was to determine the effect of hydroxyurea on adverse clinical events and haematological indices in paediatric patients with sickle cell anaemia. Method: This study compared the same cohort of patients before and after hydroxyurea therapy, monitoring the rate of adverse events, pre- and post-treatment and haematological indices. Results: Of the 40 patients, the incidence rate of painful crises post-treatment was 80% lower than pre-treatment. Post-treatment incidence rates of painful crises managed at home, requiring emergency department care or requiring admission to the ward were also lower - 79%, 81% and 84%, respectively. There was no significant difference in the incidence of other clinical events. The haemoglobin concentration increased within the first month and plateaued while the mean corpuscular volume (MCV) and mean corpuscular haemoglobin concentration (MCHC) continued to increase until six months before plateauing out. The white blood cell count (WBC) and absolute neutrophil count (ANC) decreased over the first month before levels stabilized. The reticulocyte percentage and the absolute reticulocyte count (ARC) decreased over the first three months before plateauing while the platelet count remained stable. Conclusion: Hydroxyurea significantly reduced the incidence of painful crises. There were significant increases in haemoglobin, MCV and MCHC with decreases in WBC, ANC, ARC, and reticulocyte percentage while the platelet count remained relatively stable.

RESUMEN Objetivo: El objetivo de este estudio fue determinar el efecto de la hidroxiurea sobre los eventos clínicos adversos y los índices hematológicos en pacientes pediátricos con anemia falciforme. Método: Este estudio comparó una misma cohorte de pacientes antes y después del tratamiento con hidroxiurea, monitoreando la tasa de eventos adversos, el tratamiento previo y posterior, y los índices hematológicos. Resultados: En los 40 pacientes, la tasa de incidencia de postratamiento de crisis dolorosas fue 80% inferior a la del pretratamiento. Las tasas de incidencia de postratamientos de crisis dolorosas que fueron tratadas en el hogar, atendidas en el departamento de emergencias, o requirieron ingreso hospitalario, fueron también menores -79%, 81%y 84%, respectivamente. No hubo diferencias significativas en la incidencia de otros eventos clínicos. La concentración de hemoglobina aumentó en el primer mes y se estabilizó, mientras que el volumen corpuscular medio (VCM) y la concentración de hemoglobina corpuscular media (CHCM) continuaron aumentando hasta seis meses antes de estabilizarse. nivelarse. El conteo de glóbulos blancos (CGB) y el conteo absoluto de neutrófilos (CAN) disminuyeron durante el primer mes antes de que los niveles se estabilizaran. El porcentaje de reticulocitos y el conteo absoluto de reticulocitos (CAR) disminuyeron durante los primeros tres meses antes de estabilizarse, mientras que el conteo de plateletas permaneció estable. Conclusión: La hidroxiurea redujo significativamente la incidencia de crisis dolorosas. Hubo aumentos significativos de hemoglobina, VCM y CHCM con disminuciones de CGB, CAN, CAR, y porcentaje de reticulocitos mientras que el conteo plaquetario permaneció relativamente estable.

Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

ABSTRACT Introduction and objective: In this study, we evaluated the influence of the transcript type on hematological and clinical parameters, as well as the event-free survival of 50 patients in the Chronic myeloid leukemia chronic phase. Methods: We reviewed the medical records of 55 patients with Chronic myeloid leukemia. The eligibility criteria were based on the availability of hematological and clinical baseline data in the medical records. Data on BCR-ABL transcripts were obtained from medical records. Results: Eighteen patients (36%) had the b2a2 transcript, 24 (48%) had b3a2 and 8 (16%) had b2a2/b3a2. The median platelet count for transcripts b2a2, b3a2 and b2a2/b3a2 was 320.65 × 103/L, 396 × 103/L, and 327.05 × 103/L, respectively (p = 0.896). We could not find any differences in relation to the other hematological parameters, when compared to the transcript type. Comparison between spleen and liver size and type of transcript did not differ inside the groups (p = 0.395 and p = 0.647, respectively) and the association between risk scores and transcript type did not show statistical significance (p > 0.05). The 21-month probability for event-free survival was 21%, 48% and 66% for the transcripts b2a2, b3a2 and b2a2/b3a2 respectively (p = 0.226) Conclusion: We conclude that the expression BCR-ABL transcripts have no influence on hematological, clinical and event-free survival parameters of patients in the Chronic myeloid leukemia chronic phase.

Evaluation of hydroxyurea genotoxicity in patients with sickle cell disease / Avaliação da indução de genotoxicidade pela hidroxiureia em pacientes com doença falciforme

ABSTRACT Objective To evaluate the induction of DNA damage in peripheral blood mononuclear cells of patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea. Methods The study subjects were divided into two groups: one group of 22 patients with sickle cell disease, SS and SC genotypes, treated with hydroxyurea, and a Control Group composed of 24 patients with sickle cell disease who were not treated with hydroxyurea. Peripheral blood samples were submitted to peripheral blood mononuclear cell isolation to assess genotoxicity by the cytokinesis-block micronucleus cytome assay, in which DNA damage biomarkers - micronuclei, nucleoplasmic bridges and nuclear buds - were counted. Results Patients with sickle cell disease treated with hydroxyurea had a mean age of 25.4 years, whereas patients with sickle cell disease not treated with hydroxyurea had a mean age of 17.6 years. The mean dose of hydroxyurea used by the patients was 12.8mg/kg/day, for a mean period of 44 months. The mean micronucleus frequency per 1,000 cells of 8.591±1.568 was observed in the Hydroxyurea Group and 10.040±1.003 in the Control Group. The mean frequency of nucleoplasmic bridges per 1,000 cells and nuclear buds per 1,000 cells for the hydroxyurea and Control Groups were 0.4545±0.1707 versus 0.5833±0.2078, and 0.8182±0.2430 versus 0.9583±0.1853, respectively. There was no statistically significant difference between groups. Conclusion In the study population, patients with sickle cell disease treated with the standard dose of hydroxyurea treatment did not show evidence of DNA damage induction.

RESUMO Objetivo Avaliar o efeito da indução de danos ao DNA em células monocelulares do sangue periférico de pacientes com doença falciforme, genótipos SS e SC, tratados com hidroxiureia. Métodos Os sujeitos da pesquisa foram divididos em dois grupos: um de 22 pacientes com doença falciforme genótipos SS e SC tratados com hidroxiureia, e o outro controle, composto por 24 pacientes com doença falciforme que não eram tratados com o fármaco. As amostras de sangue periférico foram submetidas ao isolamento de células mononucleares do sangue periférico para avaliação da genotoxicidade pelo ensaio de micronúcleo citoma com bloqueio da citocinese, tendo sido quantificados os biomarcadores de danos ao DNA - micronúcleos, pontes nucleoplasmáticas e brotamento nuclear. Resultados Os pacientes com doença falciforme tratados com hidroxiureia apresentaram média de idade de 25,4 anos, enquanto aqueles com doença falciforme não tratados com hidroxiureia tiveram média de idade de 17,6 anos. A dose média de hidroxiureia utilizada pelos pacientes foi de 12,8mg/kg/dia, por período médio de 44 meses. A frequência média de micronúcleos por 1.000 células de 8,591±1,568 foi observada no Grupo Hidroxiureia e de 10,040±1,003 no Grupo Controle. Adicionalmente, a frequência média de pontes nucleoplasmáticas por 1.000 células e brotamento nuclear por 1.000 células para o Grupo Hidroxiureia e Controle foi de 0,4545±0,1707 versus 0,5833±0,2078, e de 0,8182±0,2430 versus 0,9583±0,1853, respectivamente. Não houve diferença estatisticamente significativa entre os grupos. Conclusão Na população estudada de pacientes com doença falciforme com tratamento em dose padrão de hidroxiureia, não houve evidência de indução de danos ao DNA.

Clinical and hematological profile in a newborn cohort with hemoglobin SC / Perfil clínico e hematológico em uma coorte neonatal com hemoglobina SC

Abstract Objectives: Hemoglobin SC is the second most common variant of sickle-cell disease worldwide, after hemoglobin SS. The objectives of the study were to describe the clinical and laboratory characteristics of hemoglobin SC disease in children from a newborn screening program and treated at a blood center. Methodology: This study assessed a cohort of 461 infants born between 01/01/1999 and 12/31/2012 and followed-up until 12/31/2014. Clinical events were expressed as rates for 100 patient-years, with 95% confidence intervals. Kaplan-Meier survival curves were created. Results: The median age of patients was 9.2 years; 47.5% were female. Mean values of blood tests were: hemoglobin, 10.5 g/dL; reticulocytes, 3.4%; white blood cells, 11.24 × 109/L; platelets, 337.1 × 109/L; and fetal hemoglobin, 6.3%. Clinical events: acute splenic sequestration in 14.8%, blood transfusion 23.4%, overt stroke in 0.2%. The incidence of painful vaso-occlusive episodes was 51 (48.9-53.4) per 100 patient-years and that of infections, 62.2 episodes (59.8-64.8) per 100 patient-years. Transcranial Doppler ultrasonography (n = 71) was normal given the current reference values for SS patients. Hydroxyurea was given to ten children, all of whom improvement of painful crises. Retinopathy was observed in 20.3% of 59 children who underwent ophthalmoscopy. Avascular necrosis was detected in seven of 12 patients evaluated, predominantly in the left femur. Echocardiogram compatible with pulmonary hypertension was recorded in 4.6% of 130 children, with an estimated average systolic pulmonary artery pressure of 33.5 mmHg. The mortality rate from all causes was 4.3%. Conclusions: Clinical severity is variable in SC hemoglobinopathy. Several children have severe manifestations similar to those with SS disease.

Resumo Objetivos: A hemoglobinopatia SC é a segunda variante mais comum da doença falciforme no mundo, após a hemoglobinopatia SS. Os objetivos do estudo foram descrever as características clínicas e laboratoriais da hemoglobinopatia SC em recém-nascidos diagnosticados por programa de triagem neonatal e encaminhados para acompanhamento em hemocentro. Metodologia: Coorte de 461 recém-nascidos SC nascidos entre 01/01/1999 e 31/12/2012 e seguidos até 31/12/2014. A incidência de eventos clínicos foi expressa por taxas relativas a 100 pacientes-ano, com limites de confiança a 95%. Curvas de sobrevida foram construídas segundo Kaplan-Meier. Resultados: Mediana de idade, 9,2 anos; 47,5%, feminino. Médias dos valores hematológicos: hemoglobina 10,5 g/dL; reticulócitos 3,4%; leucometria 11,24 x 109/L; plaquetometria 337,1x109/L; hemoglobina fetal 6,3%. Eventos clínicos: sequestro esplênico agudo em 14,8%, hemotransfusão 23,4%, AVC isquêmico 0,2%. A incidência de episódios vaso-oclusivos dolorosos foi de 51 (48,9-53,4) por 100 pacientes-ano; a de infecções, 62,2 episódios (59,8-64,8) por 100 pacientes-ano. Doppler transcraniano (n = 71) foi normal, se usados os valores de referência de crianças SS. Dez pacientes usaram hidroxiureia, todos com melhoria das crises dolorosas. Retinopatia foi observada em 20,3% das 59 crianças que fizeram fundoscopia. Necrose avascular foi detectada em 7 de 12 pacientes avaliados, com predomínio no fêmur esquerdo. Ecocardiograma compatível com hipertensão pulmonar foi registrado em 4,6% de 130 crianças, com média estimada de 33,5 mm Hg de pressão arterial pulmonar. A taxa de mortalidade por todas as causas foi de 4,3%. Conclusões: A hemoglobinopatia SC tem gravidade variável; várias crianças apresentam manifestações clínicas intensas, semelhantes às da hemoglobinopatia SS.

The use of hydroxycarbamide in children with sickle cell anemia

Background: Although hydroxycarbamide (hydroxyurea [HU]) has been in use for decades in both adults and child populations with sickle cell disease (SCD), its reported use has remained low in Africa and Nigeria where the largest number of SCD patients reside. Availability, cost, and concerns about safety and efficacy are some of the challenges to its use. Objectives: This study highlights the experience of using HU for children with sickle cell anemia in Ahmadu Bello University Teaching Hospital, Zaria.Materials and Methods: A descriptive, retrospective observational study of children is presented. Demographic, clinical, and laboratory features of children on HU, the indications for therapy and adverse clinical events encountered were analyzed. Results: A total of 165 children were treated with HU over a 4­year period, their ages ranging between 0.9 and 17 years. A total of 85 (47.5%) had HU for >12 months, while 61 (34.1%) were on treatment <11 months, while 19 (10.2%) were lost to follow­up. There was a significant increase in the weight, height, fetal hemoglobin, mean corpuscular volume, and a significant reduction in white cell counts; with no differences in the packed cell volume, hemoglobin concentration, creatinine, alanine transaminase, and bilirubin levels. Adverse events and/or comorbidities were reported in 48 (56.5%) patients, while one patient discontinued treatment because of skin rash.Conclusion: This study highlights the increased utilization of HU among children in an African region, the observed clinical events,and laboratory parameters. The benefits are demonstrable, and the drug­related organ toxicities appear minimal

Priapismo en la drepanocitosis. Diagnóstico y opciones terapéuticas / Priapism in sickle cell disease. Diagnosis and therapeutics options

El priapismo es una complicación de la anemia drepanocítica y se define como una erección prolongada, dolorosa y persistente del pene de más de 4 horas de duración sin estimulación sexual asociada. El 95 por ciento de las crisis de priapismo en estos pacientes es de tipo isquémico o de bajo flujo y constituyen una emergencia médica que, de no diagnosticarse y tratarse adecuadamente, provoca necrosis del tejido y disfunción eréctil. En este trabajo se revisan el diagnóstico y las opciones terapéuticas actuales y futuras de esta grave complicación(AU)

Priapism is a common complication of sickle cell disease and it is characterized by a prolonged, painful and persistent erection of the penis lasting more than 4 hours without associated sexual stimulation. The 95 percent of priapism crisis in these patients is ischemic type and represents a medical emergency that can provoke erectile tissue necrosis and erectile dysfunction if not treated properly. In this paper we reviewed the diagnosisand the current and perspectives therapeutic options of this severe complication(AU)

Úlceras por hidroxiurea en paciente con policitemia vera / Ulcers to hydroxyurea in a patient with polycythemia vera

La hidroxiurea es un agente citostático que inhibe la síntesis de ADN. Se considera el tratamiento de primera línea para algunos trastornos mieloproliferativos, enfermedad de células falciformes, casos severos de psoriasis refractaria y como adyuvante en la terapia de VIH. Se ha informado de que algunos pacientes tratados con hidroxiurea pueden tener úlceras en las extremidades inferiores. Paciente femenino de 67 años de edad con antecedentes de policitemia vera tratada con hidroxiurea durante un año, se deriva a dermatología por presentar úlceras bilaterales en extremidades inferiores. Al examen físico se evidencian dos lesiones ulceradas en la región calcánea. Se realiza una biopsia de piel, y muestra signos no específicos de inflamación. Se decide la interrupción de la hidroxiurea y se inicia la terapia adyuvante con pentoxifilina. Las lesiones se resolvieron en dos meses, dejando una pequeña cicatriz residual. Es importante recordar esta rara complicación inducida por el uso prolongado de la hidroxiurea y, de esta manera, realizar un diagnóstico precoz y tratamiento adecuado, que hasta el momento es básicamente la suspensión de la hidroxiurea.

Hydroxyurea is a cytostatic agent that inhibits DNA synthesis. It is considered the first line treatment for some myeloproliferative disorders, sickle cell disease, severe cases of refractory psoriasis and as adjuvant in VIH therapy. It has been reported that some patients treated with hydroxyurea may have leg ulcers. A 67 year old female patient with a history of polycythemia vera treated with hydroxyurea for a year, is derived to dermatology for presenting bilateral lower extremity ulcers. Physical examination demonstrated two ulcerated lesions in the calcaneal region. A skin biopsy is performed, and it shows non-specific signs of inflammation. Discontinuation of hydroxyurea is decided and initiate adjuvant therapy with pentoxifylline. These ulcerative lesions were resolved within two months, leaving a small residual scar. It is important to remember this rare complication induced by prolonged use of hydroxyurea and thus, early diagnosis and appropriate treatment can be made, which so far is basically the suspension of hydroxyurea.