Pulmonary embolism in pediatrics: A 10-year experience from a tertiary center in Brazil

ABSTRACT Introduction: Although still rare, pulmonary embolism (PE) in children has been increasing over the years. Data regarding this group of patients are still sparse, which contributes to the lack of standardized prophylaxis protocols and the misdiagnosis. This study aimed to determine the incidence of pediatric PE at a Brazilian tertiary hospital, describe clinical characteristics and identify possible risk factors. We also analyzed the diagnosis and management of PE. Methods: This was a retrospective review of tertiary Brazilian single-center data of all pediatric patients (0 - 18 years) with acute PE, diagnosed radiologically, from September 2009 to May 2019. Results: The incidence of PE was 3.3 cases per 10,000 hospitalized children. All the twenty-three cases had some risk factor identified and sixteen of them (69.5%) had more than one risk factor. The most important were central venous catheter (39.1%), malignancy (34.8%) and recent surgery (34.8%). Among the children with identifiable symptoms (69.5%), the most common was dyspnea (56.2%). Only one patient did not receive antithrombotic therapy because of the high bleeding risk and most patients (70.6%) were treated for 3 to 6 months. Among the nineteen patients alive at the end of the six-month follow-up, ten (52.6%) repeated the PE image control. Seven of them (70.0%) had complete or partial resolution of the thrombosis and none had worsening images. Conclusion: Our lower incidence than that of the current literature may reflect underdiagnosis due to low suspicion of PE. At least one risk factor was identified in all patients, which emphasizes the importance of increasing awareness of high-risk children.

Prevalence and outcomes of thrombotic and hemorrhagic complications in pediatric acute promyelocytic leukemia in a tertiary Brazilian center

Abstract Introduction: Little attention is given to thrombosis associated with pediatric acute promyelocytic leukemia (APL). This study describes the thrombotic and hemorrhagic manifestations of APL in pediatric patients and evaluates their hemostasis, based on coagulation tests. Methods: Inclusion criteria were age 0-18 years and APL diagnosis between April 2005 and November 2017. Patients who had received blood transfusion prior to coagulation tests were excluded. Baseline coagulation tests, hematologic counts, and hemorrhagic/thrombotic manifestations were evaluated. Results: Median age was 10.7 years (1-15 years). The initial coagulation tests revealed a median Hgb of 8.3 g/dL (4.7-12.9 g/dL), median leucocyte count of 10.9 × 109/L (1.1-95.8 × 109/L), median platelet count of 31.8 × 109/L (2.0-109.0 × 109/L), median activated partial thromboplastin time (aPTT) of 31.7 s (23.0-50.4 s), median aPTT ratio of 1.0 (0.78-1.6), median thromboplastin time (PT) of 17.5 s (13.8-27.7 s), median PT activity of 62% (25-95 %), and median fibrinogen of 157.7 mg/dL (60.0-281.0 mg/dL). Three patients (13%) had thrombosis. At diagnosis, 21 patients (91.3%) had bruising, one patient (4.3%) had splenic vein and artery thrombosis and one patient (4.3%) presented without thrombohemorrhagic manifestations. During treatment, two patients (8.6%) had thrombosis. Conclusion: Knowledge of thrombosis in pediatric APL is important to determine its risk factors and the best way to treat and prevent this complication.

Venous thromboembolism in childhood: where is Brazil after 20 years?

Abstract Due to the longer survival of critically ill children, venous thromboembolism is a problem which is becoming increasingly recognized in pediatric practice. In the last decades, several international studies have been published, shedding a light upon the epidemiology of this disease during childhood. These data show peculiarities in the clinical presentation and the significant morbidity and mortality. The new "epidemic of thrombosis" in pediatric hospitals points toward the urgent need for specific treatment and prevention protocols targeting this population. In Brazil, knowledge regarding this disease remains scarce. The lack of epidemiological data impacts both the clinical care and the design of specific public policies in the field. Thus, a national registry of pediatric venous thromboembolism is relevant to the proposal of an appropriate plan of action to create a qualified net of assistance. The improvement in educational initiatives related to the field of Pediatric Hemostasis is also very important. In this review, we have updated the epidemiological, clinical and therapeutic aspects of the disease, as well as the prevention strategies.

Síndrome de prader willi: o que o pediatra geral deve fazer - uma revisão / Prader-willi syndrome: what is the general pediatrician supposed to do? - a review

RESUMO Objetivo: Realizar uma revisão sobre a Síndrome de Prader-Willi (SPW) com base nas publicações mais recentes e fornecer recomendações ao pediatra geral para diagnóstico precoce e seguimento. Fonte de dados: Artigos publicados nas bases Pubmed e SciELO. A pesquisa não foi limitada a um período e incluiu todos os artigos das bases de dados. Síntese dos dados: A SPW é uma síndrome genética rara, resultante da perda do imprinting gênico expresso no cromossomo paterno 15q11-q13, sendo caracterizada por alterações endocrinológicas, como deficiência de hormônio de crescimento, obesidade, insuficiência adrenal central, hipotireoidismo, hipogonadismo, além de alterações comportamentais e déficit intelectual. Há outras comorbidades associadas, como distúrbios de sono, escoliose, constipação, problemas dentários e alterações de coagulação. O protocolo de seguimento da SPW do Instituto da Criança da Universidade de São Paulo se baseia em quarto pilares principais: dieta, exercício físico, terapia com hormônio de crescimento humano recombinante (rhGH) e manejo comportamental e cognitivo. A dieta deve ser restrita a 900 kcal/dia, de acordo com a Pirâmide Alimentar do Prader-Willi, e o exercício físico deve ser diário, aeróbico e postural. A terapia com rhGH é fortemente recomendada pela literatura científica internacional e deve ser iniciada assim que for realizado o diagnóstico da síndrome. O manejo do comportamento é realizado com estratégias para estabelecer rotina e regras. Conclusões: Se a SPW se tornar mais familiar ao pediatra geral, o diagnóstico e o tratamento começarão mais precocemente, o que irá melhorar a qualidade de vida e os cuidados desses pacientes.

ABSTRACT Objective: To carry out a review about Prader-Willi Syndrome based on the most recent data about the subject and to give recommendation for the general pediatricians for early diagnoses and follow-up. Data sources: Scientific articles in the PubMed and SciELO databases. The research was not limited to a specific time period and included all articles in such databases. Data synthesis: The Prader-Willi Syndrome (PWS) is a rare genetic disorder resulting from the loss of imprinted gene expression within the paternal chromosome 15q11-q13. PWS is characterized by endocrine abnormalities, such as growth hormone (GH) deficiency, obesity, central adrenal insufficiency, hypothyroidism, hypogonadism and complex behavioral and intellectual difficulties. PWS individuals also may present other comorbidities, such as sleep disorders, scoliosis, constipation, dental issues and coagulation disorders. The follow-up protocol of the Children's Institute at Universidade de São Paulo is based on four main pillars: diet, exercise, recombinant human growth hormone (rhGH) therapy and behavioral and cognitive issues. The diet must include a caloric restriction of 900 kcal/day, according to the Prader-Willi Eating Pyramid and exercise plan is focused on daily aerobic exercises and postural therapy. The rhGH therapy is highly recommended by the international scientific literature and must be started as soon as the diagnostic is made. The management of behavioral issues is based on strategies to establish routine and rules. Conclusions: If the general pediatrician becomes more familiar with PWS, the diagnosis and treatment will start earlier, which is essential to improve the quality of life and care for these individuals.

Outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine A, / Resultado de crianças com anemia aplástica grave adquirida tratadas com globulina antitimocítica de coelho e ciclosporina A,

Objective: To evaluate the outcome of children with severe acquired aplastic anemia treated with rabbit antithymocyte globulin and cyclosporine as first-line treatment at this institution. Methods: Retrospective analysis of 26 pediatric patients with aplastic anemia, treated between 1996 and 2011 with rabbit antithymocyte globulin plus cyclosporine. Results: The overall response rate at six months was 34.6% (9/26), and the cumulative incidence of relapse was 26.5% (95% confidence interval [CI]: 1.4%-66%) at 5 years. The cumulative incidence of clonal evolution after immunosuppressive therapy was 8.3% (95% CI: 0.001%-53.7%) at five years with both clonal evolutions in non-responders who acquired monosomy 7 karyotype. The overall survival at five years was 73.6% (95% CI: 49.2%-87.5%). Conclusions: The present results confirm the poor response rate with rabbit antithymocyte globulin as first therapy in pediatrics patients, similar to what has been reported for patients of all ages. This confirmation is problematic in Brazil, given the lack of horse antithymocyte globulin in many markets outside the United States. .

Objetivo: Avaliar o resultado de crianças com anemia aplástica grave adquirida tratadas com globulina antitimocítica de coelho e ciclosporina como tratamento inicial em nosso instituto. Métodos: Análise retrospectiva de 26 pacientes pediátricos com anemia aplástica tratados entre 1996 e 2011 com globulina antitimocítica de coelho e ciclosporina. Resultados: A taxa de resposta geral em seis meses foi de 34,6% (9/26), e a incidência acumulada de recorrência foi de 26,5% (intervalo de confiança [IC] de 95%,1,4%-66%) em cinco anos. A incidência acumulada de evolução clonal após a terapia imunossupressora foi de 8,3% (IC 95%, 0,001%-53,7%) em cinco anos, com ambas as evoluções clonais em pacientes sem resposta que adquiriram o cariótipo com monossomia 7. A sobrevida geral em cinco anos foi de 73,6% (IC 95%, 49,2%-87,5%). Conclusões: Nossos resultados confirmam a baixa taxa de resposta com globulina antitimocítica de coelho como terapia inicial em pacientes pediátricos, da mesma forma como relatado para pacientes de todas as idades. Essa confirmação é problemática em nosso país devido à falta de globulina antitimocítica de cavalo em muitos mercados fora dos Estados Unidos, incluindo o Brasil. .

Deficiência congênita de fator X: quando pensar? / Congenital factor X deficiency: when thinking?

Objetivo: Descrever o caso de um lactente portador de deficiência congênita de fator X e discutir o diagnóstico diferencial dessa coagulopatia rara. Relato do caso: Lactente, 54 dias de vida, sexo masculino, foi encaminhado paraavaliação hematológica devido a episódios prévios de hemorragia de etiologia a esclarecer. No segundo dia de vida, apresentou epistaxe e aumento do perímetro cefálico e, na segunda semana de vida, apresentou enterorragia. Foram realizados examesque evidenciaram TP e TTPA prolongados e antecedentes familiares sugestivos de diátese hemorrágica. Em nosso serviço, foram descartadascausas adquiridas que poderiam justificar o prolongamento dos tempos de coagulação (deficiência de vitamina K, infecção, hepatopatias) e também foram descartados sangramentos emoutros locais (sistema nervoso central e abdome). As dosagens dos fatores de coagulação II e V foram normais, sendo detectados níveis de fator X inferioresa 1% (FX < 1%), evidenciando deficiência grave desta proteína. Durante a investigação, o paciente apresentou novo episódio de enterorragia, sem descompensação hemodinâmica e recebeu plasma fresco congelado. Atualmente, está em seguimento ambulatorial, em uso profilático de concentrado de complexo protrombínico, sem manifestaçõeshemorrágicas. Conclusão: As coagulopatias congênitas são doenças hemorrágicas resultantes da deficiência quantitativa ou qualitativa de umaou mais das proteínas plasmáticas da coagulação. Os pacientes acometidos podem apresentar sangramentos de gravidade variável, espontâneosou pós-traumáticos, presentes ao nascimento ou diagnosticados ocasionalmente. Estas coagulopatiassão caracterizadas por herança genética, quadro clínico e laboratorial distintos entre si e, entre elas, as hemofilias e a doença de Von Willebrand são as mais comuns. São consideradas coagulopatias raras as deficiências de fatores I, II, V,...

Objective: To describe the case of an infant with congenital factor X deficiency and to discuss the differential diagnosis of other rare coagulopathies. Case report: Infant, 54-day-old male was referred for hematologic evaluation due to previous episodes of bleeding of unknown etiology. On the second day of life, he had epistaxis and increased head circumference and, in the second week of life, had rectal bleeding. Laboratory assays were performed and showed prolonged PT and APTT and family history suggestive of bleeding disorders. In our department, other acquired causes that could justify the prolongation of clotting time (vitaminK deficiency, infection, liver disease) were excluded and bleeding were also evaluated at other sites (central nervous system and abdomen). The levels of coagulation factors II and V were normal and detected levels of factor X less than 1% (FX<1%),suggesting serious deficiency of this protein. During the investigation, the patient presented a new episode of rectal bleeding, without hemodynamicinstability, and received fresh frozen plasma. He is currently in follow-up, receiving prophylactic prothrombin complex concentrate, without hemorrhagic manifestations. Conclusion: the congenital coagulopathies are bleeding disorders resulting from a quantitative or qualitative deficiency of one or more of the plasma procoagulant protein. The affected patients may have bleeding of varying sev rity, spotaneous or post traumatic, present at birthor diagnosed occasionally. These bleding disorders are characterized by specific genetic inheritance and clinical and laboratory characteristics. Amonginherited bleedingdisorders, the hemophilia and Von Willebrand disease are the most common. The deficienciesof factors I, II, V, VII, X and XIII are considered rare coagulation disorders and the differential diagnosis among these diseases is essential to guideappropriate therapy. In cases of severe deficiency of factor X, as patients may have...

Anemia causada por parvovírus B19 em lactente com deficiência de G6PD / Anemia caused by parvovirus B19 infection in an infant with G6PD deficiency

Objetivo: destacar a infecção por parvovirus B19 como uma das causas de anemia em lactentes com doença hemolítica de base...

Objective: to highlight B19 parvovirus infection as a cause of anemia in infants with underlying hemolytic disease...

Púrpura trombocitopênica e anemia hemolítica auto-imune em pacientes internados com lúpus eritematoso sistêmico juvenil / Trombocytopenic purpura and autoimmune hemolytic anemia in hospitalized patients with juvenile systemic lupus erythematosus

OBJETIVO: avaliar o comprometimento hematológico (CHE) em pacientes internados com lúpus eritematoso sistêmico juvenil (LESJ). MÉTODOS: durante o período de 1994 a 2005, ocorreram 195 internações de 77 pacientes com LESJ (critérios do Colégio Americano de Reumatologia) e foram acompanhadas pela Unidade de Reumatologia Pediátrica do Instituto da Criança - Universidade de São Paulo. Essas internações foram avaliadas com relação à presença de CHE inicial ou evolutivo: anemia hemolítica auto-imune ou púrpura trombocitopênica. Todos os pacientes realizaram dois ou mais hemogramas. O diagnóstico de anemia hemolítica auto-imune (AHAI) foi estabelecido pela queda acentuada dos níveis de hemoglobina (acima de 2 g/dl), reticulocitose, aumento de desidrogenase láctica (DHL), aumento de bilirrubina indireta e teste de Coombs positivo. As manifestações hematológicas associadas à infecção, neoplasia e anemia aplásica foram excluídas. RESULTADOS: o CHE ocorreu em 14 pacientes (18,9 por cento), com 15 internações. Destes, 11 eram do sexo feminino, sete apresentaram púrpura trombocitopênica, cinco, anemia hemolítica auto-imune e dois, síndrome de Evans. O CHE, como manifestação inicial e isolada do LESJ, foi evidenciado em três pacientes. Todos os pacientes com púrpura trombocitopênica apresentaram sangramento cutâneo (petéquias e/ou equimoses). Todos estavam em atividade da doença e apresentavam simultaneamente outras manifestações do LESJ, particularmente nefrite e vasculite. Inicialmente, todos receberam pulsoterapia com metilprednisolona e, posteriormente, prednisona. Em três pacientes, o tratamento foi predominantemente realizado para controle das manifestações hematológicas, com gamaglobulina endovenosa. Os imunossupressores mais utilizados foram pulsoterapia endovenosa com ciclosfosfamida, ciclosporina e azatioprina. Obito ocorreu em uma paciente por sangramento de sistema nervoso central. Nenhum paciente necessitou de esplenectomia. CONCLUSÕES: o...

OBJECTIVE: to evaluate the hematological involvement (HI) in hospitalized patients with juvenile systemic lupus erythematosus (JSLE). METHODS: from 1994 to 2005, 195 admissions occurred in 77 JSLE patients (American College of Rheumatology criteria) and were followed by the Pediatric Rheumatology Unit of the Instituto da Criança - University of São Paulo. These admissions were evaluated according to the presence of HI at onset or during the evolution of the disease: autoimmune hemolytic anemia (AHA) or thrombocytopenic purpura. All patients performed at least two complete blood counts. AHA was defined by a fall in hemoglobin levels (beyond 2 g/dl), reticulocytosis, increase in lactate dehydrogenase (LDH) and indirect bilirubin levels, and a positive Coombs test. The hematologic manifestations associated with infection, neoplasia and aplastic anemia were excluded. RESULTS: HI occurred in 14 patients (18.9 percent), with 15 admissions. Among these patients, 11 were female, 7 had trombocytopenic purpura, 5 AHA and 2 Evans syndrome. HI as onset and single manifestation of JSLE was observed in three patients. All the patients with trombocytopenic purpura presented cutaneous bleeding (petechia and/or ecchymosis). All had disease activity and simultaneously presented other manifestations of JSLE, particularly nephritis and vasculitis. Initially, all patients received pulsetherapy with methylprednisolone and prednisone later. In three patients the treatment aimed predominantly the control of hematologic manifestations, with intravenous gammaglobulin. The most used immunossupressive therapies were intravenous cyclophosphamide, cyclosporine and azathioprine. One patient died of central nervous system bleeding. No patient needed splenectomy. CONCLUSIONS: isolated HI was a severe manifestation in hospitalized patients with JSLE, generally associated with an active and systemic disease.

Deficiência de ferro e anemia feropriva em crianças de Vitória, ES / Iron deficiency and anemia in children from Vitoria, ES, Brazil

Os níveis de hemoglobina variam com a idade: os níveis adotados no artigo estão adequados para as faixas etárias estudadas. O critério utilizado para o diagnóstico de anemia ferropriva - a dosagem de ferritina, é adequado, embora incompleto; há possibilidade de falso-negativo. Embora os autores tenham-se referido à possível realização de outras dosagens, como avaliar o índice de saturação de transferrina, este dado não foi analisado no estudo...

Complicações tromboembolíticas da leucemia linfoblástica aguda em crianças e adolescentes: efeitos da doença e do tratamento sobre o sistema hemostático / Thromboembolic complications of acute lymphoblastic leukemia in children and adolescents: effects of the disease and the therapy on the hemostatic system

O recente aumento na incidência dos eventos tromboembólicos e a necessidade de seu tratamento em crianças e adolescentes têm justificado o desenvolvimento de estudos e programas específicos. As tromboses são causas importantes de morbidade e mortalidade em pacientes com câncer. Em especial, na leucemia linfoblástica aguda (LLA) da infância, o tromboembolismo é uma complicação grave que ocorre em conseqüência da interação entre a doença, o hospedeiro e o tratamento. Este estudo teve por objetivos avaliar prospectivamente o comportamento dos marcadores de ativação da coagulação e das proteínas anticoagulantes naturais em pacientes com LLA no momento do diagnóstico e durante o tratamento de indução de remissão. Correlacionar os resultados da avaliação da hemostasia com a ocorrência de eventos tromboembólicos e com a presença da mutação G1691A do fator V e do polimorfismo G20210A do gene da protrombina. No período de fevereiro a novembro de 2003 foram avaliados 16 crianças e adolescentes com diagnóstico de LLA admitidos na Unidade de Oncologia do Instituto da Criança do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. As avaliações clínicas e laboratoriais foram realizadas no momento do diagnóstico, durante e ao final do tratamento de indução de remissão (Protocolo GBTLI LLA-99) / The recent increase in the incidence of thromboembolic events and the need of treatment in children and adolescents justify the development of specialized programs to provide optimal management. Thromboembolic disease is a major cause of morbidity and mortality in cancer patients. Especially in acute lymphoblastic leukemia (ALL) of infancy, thromboembolic events are severe complications that occur as a result of the interaction of the disease, the host and the treatment. The main purpose of this study was to evaluate thrombin generation and thrombin inhibitors in patients with ALL at presentation and during the induction therapy...

Meningite neonatal por Streptococcus pyogenes e trombose de seio sagital: relato de caso / Neonatal Streptococcus pyogenes meningitis and sagital sinus thrombosis: case report

Relatamos um caso de meningite por Streptococcus pyogenes em menina de 18 dias de vida, com evoluçao complicada por trombose de seio sagital. Sao discutidos alguns aspectos da patogênese, tratamento e seguimento da doença. Frente ao aumento mundial das infecçoes estreptocócicas graves nos últimos 10 anos, é provável que a meningite neonatal por Streptococcus pyogenes se torne mais frequente no futuro, sendo importante estar alerta para o diagnóstico precoce e as possíveis complicaçoes dessa infecçao potencialmente letal.