Ivan L. Angulo

Programa de Triagem Neonatal do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil

The Neonatal Screening Program at the University Hospital of the Ribeirão Preto School of Medicine, São Paulo University, Brazil, was introduced in 1994. As of December 2005, congenital hypothyroidism had been diagnosed in 76 infants, phenylketonuria in 10, and hemoglobinopathies in 25, representing incidence rates of 1:2,595, 1:19,409, and 1:4,120, respectively. A total of 2,747 newborns had the sickle cell trait, i.e., were heterozygous for the sickle mutation (1:37.5 live births). The programs mean coverage during this period was 94.5%. There was major improvement in the parameters for evaluating the programs quality, although they were still far from ideal. Public-awareness campaigns on the importance of neonatal screening are needed to increase the programs coverage. Setting postnatal day 3 as the standard Day for the Heel Stick Test would help ensure treatment at earlier ages, thus improving prognosis for affected infants.O Programa de Triagem Neonatal do Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Brasil, instituido em 1994 diagnosticou, ate 2005, 76 criancas com hipotireoidismo congenito, 10 com fenilcetonuria e 25 com hemoglobinopatias, o que representou uma incidencia de 1:2.595, 1:19.409, 1:4.120, respectivamente. Foram diagnosticadas 2.747 criancas com traco falciforme (1:37,5 nascidos vivos). A cobertura media do programa foi de 94,5%. Houve uma consideravel melhora nos parâmetros de avaliacao da qualidade do programa no periodo, porem, sem atingir os indices ideais. Campanhas visando a maior divulgacao da importância da triagem neonatal sao necessarias para aumentar a cobertura e a instituicao do 3o dia de vida do recem-nascido como sendo o Dia do Teste do Pezinho poderia contribuir para que idades mais precoces de tratamento fossem atingidas, melhorando o prognostico das criancas acometidas.

Protocolo clínico e diretrizes terapêuticas para uso de hidroxiureia na doença falciforme

Hidroxiureia (HU) constitui o avanco mais importante no tratamento de pacientes com doenca falciforme (DF). Fortes evidencias confirmam a eficacia da HU em pacientes adultos diminuindo os episodios de dor intensa, hospitalizacao, numero de transfusoes e sindrome toracica aguda. Embora a evidencia da eficacia do tratamento com HU em criancas nao seja tao forte, os recentes resultados sao encorajadores. Os dados atuais em relacao aos riscos a curto e longo prazos da terapia com HU em adultos sao aceitaveis comparado aos riscos dos pacientes nao tratados com HU. Neste artigo, apresentamos revisao detalhada sobre os principais aspectos quanto a eficacia, efetividade, toxicidade e barreiras ao uso de HU em pacientes com DF e propomos um protocolo clinico e diretrizes terapeuticas para o uso de HU em pacientes com DF.

Clinical and hematological effects of hydroxyurea therapy in sickle cell patients: a single-center experience in Brazil

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.

Consenso brasileiro em transplante de células-tronco hematopoéticas: comitê de hemoglobinopatias

Os disturbios hereditarios das hemoglobinas sao as doencas geneticas mais frequentes do homem e mais difundidas no mundo, abrangendo sobretudo continentes como Africa, Americas, Europa e extensas regioes da Asia. Estima-se que haja 270 milhoes de portadores de hemoglobinopatias no mundo, dos quais 80 milhoes sao portadores de talassemia. Aproximadamente 60 mil criancas nascem anualmente no mundo com talassemia e 250 mil com anemia falciforme, dando uma frequencia de 2,4 criancas afetadas para cada 1.000 nascimentos. No Brasil, a doenca falciforme e a doenca hereditaria monogenica mais comum, estimando-se que haja entre 20 a 30 mil pacientes portadores desta doenca. O transplante de celulas-tronco hematopoeticas alogenico (TCTH alo) e atualmente a unica modalidade terapeutica capaz de curar pacientes com hemoglobinopatias. Neste artigo discutiremos os dados disponiveis na literatura e sugerimos os criterios para a indicacao do TCTH nas hemoglobinopatias.

Intrahepatic Cholestasis in Sickle Cell Disease: A Case Report

Intrahepatic cholestasis (SCIC) is an uncommon but potentially fatal complication of sickle cell disease (SCD), with a high death rate, observed mainly in patients with homozygous sickle cell anemia. Herein, we describe a case of severe SCIC treated successfully with aggressive manual exchange transfusion (ET). The patient was admitted with enlarged liver and signs of hepatic failure, such as hyperbilirubinemia and coagulopathy. There was no evidence of viral hepatitis or biliary obstruction. We performed several sessions of ET in order to reduce the percentage of HbS to levels inferior to 30%, which was successfully accomplished. The patient had a complete recovery of hepatic function. This case has shown that ET is an effective treatment of SCIC and should be introduced early on the onset of this severe complication.

Acidente vascular cerebral e outras complicações do sistema nervoso central nas doenças falciformes

In children with sickle cell disease, cerebral arteries are prone to lesions that may cause deficiencies and poor quality of life. After the age of 20, new lesions may also occur. Besides stroke and silent cerebral ischemia, other lesions may occur. Radiologic images are necessary to diagnose and blood transfusions to treat. We reviewed the literature to choose best practices and guidelines to reduce morbidity and mortality and improve the quality of life of children with sickle cell disease. Risk factors identified from clinical and laboratory data and screening by Doppler ultrasonography and magnetic resonance must be used in order to make decisions about transfusion and iron chelation therapy.

Determination of iron-overload in thalassemia by hepatic MRI and ferritin

O acumulo de ferro na talassemia causa lesoes orgânicas e reduz a sobrevida do paciente por lesao cardiaca na segunda decada da vida, e tem sido avaliado por medidas diretas (biopsia) e indiretas (ferritina). As medidas isoladas carecem de valor, sendo preferidas as sequenciais. Este trabalho pretende comparar medidas indiretas de sobrecarga de ferro, uma medida da concentracao de ferro hepatico por ressonância magnetica, e a ferritina serica media dos ultimos quatro anos. Trata-se de estudo retrospectivo de 25 pacientes do Centro Regional de Hemoterapia, em Ribeirao Preto, Brasil. Encontrou-se em vinte pacientes ferro hepatico acima de 7 mg/g peso seco e ferritina media elevada acima de 2.500 ug/l em dez. Estratificacao em tres niveis de sobrecarga (leve, moderada e grave) produziu resultados semelhantes em ambos os testes. Varios outros fatores influenciam o grau de sobrecarga de ferro na talassemia. Nao houve correlacao significativa com aplicacao de testes nao-parametricos. Ambos os metodos usados concomitantemente levarao a um melhor planejamento da terapia quelante.

Sickle cell disease and pregnancy: analysis of 34 patients followed at the Regional Blood Center of Ribeirão Preto, Brazil.

Objective The objective of this study was to verify the evolution of pregnancies in sickle cell patients followed at one institution over a period of 12 years (January 2000 to June 2012). Methods The study evaluated 34 pregnant women with sickle cell disease with a mean age of 23.9 ± 5.3 years. The incidence of obstetric complications, non-obstetric complications linked to sickle cell disease and complications in the newborn were analyzed. Results A total of 26% of the cases reported previous miscarriages, 20% had preterm labor, 10% had pre-eclampsia, and 5% had gestational diabetes. Forty-one percent of the deliveries were cesarean sections and 29% of patients required blood transfusions. In respect to sickle cell disease, 62% of patients had vaso-occlusive crises, 29% had acute chest syndrome, 23% had urinary tract infection, 15% had impaired cardiac function and 6% developed pulmonary hypertension. Only one patient died in the postnatal period due to acute chest syndrome. The mean gestational age was 37.8 ± 2.63 weeks, and mean newborn weight was 2.809 ± 643.8 g. There were seven fetal losses, including three stillbirths and four miscarriages. The impact of transfusion therapy on the incidence of maternal–fetal complications during pregnancy was evaluated. Conclusions Pregnancy in sickle cell patients is still associated with complications. Although no statistical difference was observed between transfused and non-transfused women, there were no deaths (fetal or maternal) in transfused patients whereas one maternal death and three stillbirths occurred in non-transfused women. A larger study of sickle cell pregnant women will be necessary to elucidate the actual role of transfusion during pregnancy in sickle cell disease.

Modern hemotherapy, ancient practices

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Hematological differences between patients with different subtypes of sickle cell disease on hydroxyurea treatment

Objective Sickle cell anemia and the interaction S/Beta thalassemia differ in hematological values due to microcytosis and hypochromia caused by the thalassemic mutation. The clinical benefit of long-term hydroxyurea treatment is undeniable in sickle cell disease with monitoring of the biological action of the drug being by the complete blood count. The objective of this work is to compare changes in some of the erythrocytic indexes between S/Beta thalassemia and sickle cell anemia patients on long-term hydroxyurea treatment. Methods The values of erythrocyte indexes (mean corpuscular volume and mean corpuscular hemoglobin) were compared in a retrospective study of two groups of patients (Sickle cell anemia and S/Beta thalassemia) on hydroxyurea treatment over a mean of six years. Results The quantitative values of the two parameters differed between the groups. Increases in mean corpuscular volume and reductions in mean corpuscular hemoglobin delay longer in S/Beta thalassemia patients (p-value = 0.018). Conclusion Hematological changes are some of the beneficial effects of hydroxyurea in sickle cell disease as cellular hydration increases and the hemoglobin S concentration is reduced. The complete blood count is the best test to monitor changes, but the interpretation of the results in S/Beta thalassemia should be different.