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.

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.

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.

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.

Sickle cell anemia in Brazil: personal, medical and endodontic patterns

Abstract Sickle cell anemia (SCA) is the most prevalent genetic disease worldwide. Recurrent vaso-occlusive infarcts predispose SCA patients to infections, which are the primary causes of morbidly and mortality. This study aimed to evaluate the relationship between SCA and endodontic diseases. Personal information, medical data (hematological indices, virologic testing, blood transfusions, medications received, splenectomy) and information on the need for endodontic treatment were obtained from SCA patients who were registered and followed up by the Fundação Hemominas, Minas Gerais, Brazil.These data were compared with the need for root canal treatment in SCA patients. One hundred eight patients comprised the studied population, and the rate of the need for endodontic therapy was 10.2%. Among the medical data, a significant difference was observed for eosinophil (p = 0.045) counts and atypical lymphocyte counts (p = 0.036) when the groups (with and without the need for endodontic treatment) were compared. Statistical relevance was observed when comparing the patients with and without the need for root canal therapy concerned eosinophil counts and atypical lymphocyte counts. The differences in statistical medical data, observed between the groups suggest that both parameters are naturally connected to the stimulation of the immune system that can occur in the presence of root canal infections and that can be harmful to SCA individuals.

Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study / Estado oxidante-antioxidante em crianças egípcias com anemia falciforme: estudo baseado em um único centro

OBJECTIVE: the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia. METHODS: the serum levels of total antioxidant capacity (TAO), paraoxonase (PON), vitamin E, nitrite, and malondialdehyde (MDA) were measured in 40 steady state children with homozygous sickle cell anemia (24 males and 16 females) and 20 apparently healthy age- and gender-matched controls. RESULTS: mean serum TAO, PON, vitamin E, and nitrite levels were significantly lower in the group with sickle cell anemia, whereas mean serum MDA was significantly higher in these children compared to controls. No significant differences in mean levels of TAO, PON, nitrite, vitamin E, and MDA were found in sickle cell anemia patients receiving hydroxyurea when compared with those not receiving hydroxyurea. A significant negative correlation between serum nitrite and the occurrence of vaso-occlusive crises (VOC) was observed (r = -0.3, p = 0.04). PON level was found to be positively correlated with patients' weight and BMI (r = -0.4, p = 0.01; r = -0.7, p < 0.001, respectively), but not with frequency of VOC. The area under the curve of serum nitrite in predicting occurrence of VOC was 0.782, versus 0.701 for PON, and 0.650 for TAO (p = 0.006). Serum MDA was not correlated with nitrite, PON, TAO, or vitamin E levels. No significant correlations were detected between serum nitrite and hemoglobin or antioxidant enzymes. CONCLUSION: children with sickle cell anemia have chronic oxidative stress that may result in increased VOC, and decreased serum nitrite may be associated with increases in VOC frequency. A novel finding in this study is the decrease in PON level in these patients, which is an interesting subject for further research. .

OBJETIVO: o presente estudo foi realizado com o objetivo de investigar o estado oxidante-antioxidante em crianc¸as egípcias com anemia falciforme. MÉTODOS: dosamos os níveis séricos da capacidade antioxidante total (CAT), paraoxonase (PON), vitamina E, nitrito e malondialdeído (MDA) em 40 crianças estáveis com anemia falciforme homozigótica (24 meninos e 16 meninas), e 20 controles pareados por idade/sexo aparente-mente saudáveis. RESULTADOS: os níveis séricos médios da CAT, PON, vitamina E e nitrito foram significativamente menores, ao passo que o nível sérico médio de MDA foi significativamente maior em crianças com anemia falciforme (AF), em comparação aos controles. Não foram encontradasdiferenças significativas nos níveis médios de CAT, PON, nitrito, vitamina E e MDA em pacientescom AF em tratamento com hidroxiureia, em comparação aos que receberam hidroxiureia. Encontramos uma correlação negativa significativa entre o nitrito sérico e a ocorrência decrises vaso-oclusivas agudas (CVO) (r = -0,3, p = 0,04). Descobrimos que o nível de PON está correlacionado positivamente com o peso e o IMC dos pacientes (r = -0,4; p = 0,01; r = -0,7; p < 0,001, respectivamente), porém não com a frequência de CVO. A área sob a curva (ASC) donitrito sérico na previsão da ocorrência de CVO foi 0,782, em comparação a 0,701 para PON e 0,650 para CAT (p = 0,006). O MDA não está correlacionado a nitrito, PON, CAT ou vitamina E. Não foram detectadas correlações significativas entre nitrito sérico e hemoglobina ou enzimas antioxidantes. CONCLUSÃO: crianças com AF apresentam estresse oxidativo crônico que pode resultar emaumento das CVO. Em crianças com AF, a redução nos níveis de ...

Clinical and hematological effects of hydroxyurea therapy in sickle cell patients: a single-center experience in Brazil / Efeitos clinicos e hematologicos do tratamento com hidroxiureia em pacientes falciformes: experiencia de um centro no Brasil

CONTEXT AND OBJECTIVES Sickle cell disease (SCD) is the most common genetic disorder among people of African descent, affecting approximately 3,500 newborns each year in Brazil. Hydroxyurea (HU) is the only effective drug to treating patients with SCD, thereby reducing morbidity and mortality. The objective was to analyze the effects of HU on SCD patients at our institution. DESIGN AND SETTING Retrospective study conducted at a sickle cell centre in Ribeirão Preto, São Paulo, Brazil. METHODS We analyzed clinical and laboratory data on 37 patients. The hematological parameters and clinical events that occurred during the year before and the first year of treatment with HU were analyzed. The mean dose of HU was 24.5 ± 5.5 mg/kg/day. RESULTS There were rises in three parameters: hemoglobin (8.3 g/dl to 9.0 g/dl, P = 0.0003), fetal hemoglobin (HbF) (2.6% to 19.8%, P < 0.0001) and mean cell volume MCV (89 to 105 fl, P = 0.001); and reductions in the numbers of leukocytes (10,050/µl to 5,700/µl, P < 0.0001), neutrophils (6,200/µl to 3,400/µl, P = 0.001), platelets (459,000/µl to 373,000/µl, P = 0.0002), painful crises (1.86 to 0.81, P = 0.0014), acute chest syndromes (0.35 to 0.08, P = 0.0045), infections (1.03 to 0.5, P = 0.047), hospitalizations (1.63 to 0.53, P = 0.0013) and transfusions (1.23 to 0.1, P = 0.0051). CONCLUSION The patients presented clinical and hematological improvements, with an increase in HbF and a reduction in the infection rate, which had not been addressed in most previous studies. .

CONTEXTO E OBJETIVO A doença falciforme (SCD) é o distúrbio genético mais comum entre afrodes-cendentes, afetando aproximadamente 3.500 recém-nascidos a cada ano no Brasil. A hidroxiureia (HU) é a única droga efetiva para o tratamento dos pacientes com SCD, reduzindo a morbidade e a mortalidade da doença. O objetivo do estudo foi analisar os efeitos da HU em pacientes com SCD em nossa instituição. TIPO DE ESTUDO E LOCAL Estudo retrospectivo realizado em um centro de anemia falciforme em Ribeirão Preto, São Paulo, Brasil. MÉTODOS Nós analisamos os dados clínicos e laboratoriais de 37 pacientes. Os parâmetros hematológicos e eventos clínicos que ocorreram no ano anterior e durante o primeiro ano de tratamento com HU foram analisados. A dose média de HU foi 24.5 ± 5.5 mg/kg/dia. RESULTADOS Houve aumento em três parâmetros estudados: hemoglobina (8,3 g/dl para 9,0 g/dl, P = 0,0003), hemoglobina fetal (HbF) (2,6% para 19,8%, P < 0,0001) e volume corpuscular médio (VCM) (89 para 105 fl, P = 0,001); e redução do número de leucócitos (10.050/µl para 5.700/µl, P < 0,0001), neutrófilos (6.200/µl para 3.400/µl, P = 0,001), plaquetas (459.000/µl para 373.000/µl, P = 0,0002), crises dolorosas (1,86 para 0,81, P = 0,0014), síndrome torácica aguda (0,35 para 0,08, P = 0,0045), infecções (1,03 para 0,5, P = 0,047), hospitalizações (1,63 para 0,53, P = 0,0013) e número de transfusões (1,23 para 0,1, P = 0,0051). CONCLUSÃO Os pacientes apresentaram melhora clínica e hematológica, com aumento da HbF e redução da taxa de infecção, dado este não explorado na maioria dos estudos clínicos já publicados. .

Efeitos colaterais cutâneos após uso prolongado de hidroxiuréia na Policitemia Vera / Cutaneous effects after prolongaded use of hydroxyurea in Polycythemia Vera

A hidroxiureia é um derivado hidroxilado da ureia utilizado em diversas desordens hematológicas. Inúmeras alterações cutâneas, porém raras, são relatadas após seu uso prolongado. A patogênese das mesmas não está bem esclarecida, porém, sugere-se que a droga tenha uma ação tóxica direta sobre a pele. Descrevemos um homem de 75 anos, branco, com diagnóstico de Policitemia Vera que, ao longo de 11 anos de tratamento com hidroxiureia, evoluiu com várias lesões cutâneas: hiperpigmentação da pele, lesões atróficas em antebraços, melanoníquia longitudinal das 20 unhas, úlcera em antebraço direito, xerose cutânea, ictiose em pernas e carcinoma espinocelular no pavilhão auricular direito. Até o momento, os relatos na literatura descrevem pouca diversidade de lesões nos pacientes acometidos.

Hydroxyurea is an hydroxylated urea derivative used in many myeloproliferative disorders. Many, but unusual cutaneous disorders are related after its prolonged use. Their pathogenesis is not clear, but it is suggested that there is direct toxicity of the drug on the skin. We described a white, 75-year old man with diagnosis of Polycythemia Vera that in 11 years of treatment developed many cutaneous lesions: skin hyperpigmentation, atrophic lesions on forearms, longitudinal melanonychia of 20 nails, right forearm ulcer, cutaneous xerosis, ichthyosis and auricular spinocellular carcinoma. At this moment, the literature reports describe little diversity of lesions in affected patients.

Atrial septal defect closure on cardiopulmonary bypass in a sickle cell anemia: Role of hydroxyurea and partial exchange transfusion.

Partial exchange transfusion during cardiopulmonary bypass, while conducting cardiac surgery may be a useful technique in patients with high level of sickle hemoglobin. Along with this preoperative use of hydroxyurea and alternative analgesic modalities such as transcutaneous electrical nerve stimulation in postoperative period may be beneficial, in our opinion. A 16-year-old female of Turner's syndrome having sickle cell anemia scheduled for closure of arterial septal defect on cardiopulmonary bypass was managed with partial exchange transfusion and warm cardioplegia.

Advances in management of sickle cell disease.

Sickle cell disease is numerically as common as thalassaemia. However, it affects relatively under privileged population i.e. tribal population belonging to economically poor class and having inadequate access to education and modern health facilities. A recent explosion acknowledged in understanding the pathogenesis of this disease has lead to newer dimensions in treatment. Some of these viz. prevention of overwhelming bacterial infection, present indications and controversies regarding blood transfusion, prevention of stroke, acute chest syndrome, hydroxyurea therapy--probably the best disease modifying agent at the moment, stem cell transplantation--a cure and certain promising experimental therapies including gene therapy have been discussed in this review.

The activity of superoxide dismutase in hydroxyurea-treated E beta thalassemia.

AIM: To study the activity of superoxide dismutase (SOD) and the level of fetal hemoglobin (HbF) in hydroxyurea (HU)-treated E beta thalassaemia. METHODS: We have measured SOD level, HbF, mean corpuscular volume (MCV), packed cell volume (PCV) and hemoglobin (Hb) of E beta thalassaemia treated with HU (dose 30 mg/kg/day) for consecutive 90 days. RESULT: The increase of HbF synthesis without increase of Hb was observed in HU-treated patients. CONCLUSION: The decreased SOD level in long term and low dose of HU therapy in E beta thalassaemia may have some role to inhibit superoxide radical of erythrocyte. HU may act as inhibitor for oxidative damage of red cell in E beta thalassaemia.

Tratamento da crise de anemia falciforme pela dipirona, hidrocortisona e hidratacao / Treatment of sickle cell crises by dipirone, hidrocortisone and hidration

Observamos "in vitro" que a dipirona melhora a solubilidade da hemoglobina S e que os corticosteroides tem uma acao antiinflamatoria aliviando as dores nas crises falcemicas. Foram tratadas 116 criancas apresentando crises dolorosas da doenca de celulas falciformes...