RESUMO
Comparative clinical studies of children and adults with immune thrombocytopenia (ITP) are poorly covered in the literature. However, the accepted classification of ITP-childhood ITP and adult ITP-results in considerable differences in treatment protocols and practice guidelines. The analysis of the Pediatric and Adult Registry on Chronic ITP (PARC-ITP) of patients at first presentation demonstrated fewer differences in clinical and laboratory findings at initial diagnosis between children and adults than expected. The present report of 2-year follow-up data supports the hypothesis that there are common aspects of childhood and adult ITP. Data of 3360 children and 420 adults were collected during the time of 2004 until 2015 at initial diagnosis. Follow-up information was available for 51% and 33% of children and 66% and 49% of adults at 12- and 24-months, respectively. Similarities were found in unexpected areas of ITP, such as the rate of late remission at 12 and 24 months, reported bleeding sites, platelet count in bleeders, and the frequency of treated patients with persistent or chronic ITP. Differences were confirmed for the overall rate of remission and treatment modalities. Unexpected differences were found in the percentage of nonbleeders, with more adults in the nonbleeder group. More studies are needed to investigate different age groups with the aim to optimize their management.
Assuntos
Púrpura Trombocitopênica Idiopática/classificação , Púrpura Trombocitopênica Idiopática/patologia , Adulto , Fatores Etários , Criança , Doença Crônica , Seguimentos , Hemorragia , Humanos , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/terapia , Indução de RemissãoRESUMO
Aquaporin-1 (AQP1) is the membrane water channel responsible for changes in erythrocyte volume in response to the tonicity of the medium. As the aberrant distribution of proteins in hereditary spherocytosis (HS) generates deficiencies of proteins other than those codified by the mutated gene, we postulated that AQP1 expression might be impaired in spherocytes. AQP1 expression was evaluated through flow cytometry in 5 normal controls, 1 autoimmune hemolytic anemia, 10 HS (2 mild, 3 moderate, 2 severe, and 3 splenectomized), and 3 silent carriers. The effect of AQP1 inhibitors was evaluated through water flow-based tests: osmotic fragility and hypertonic cryohemolysis. Serum osmolality was measured in 20 normal controls and 13 HS. The effect of erythropoietin (Epo) on AQP1 expression was determined in cultures of erythroleukemia UT-7 cells, dependent on Epo to survive. Independent of erythrocyte size, HS patients showed a lower content of AQP1 in erythrocyte membranes which correlated with the severity of the disease. Accordingly, red blood cells from HS subjects were less sensitive to cryohemolysis than normal erythrocytes after inhibition of the AQP1 water channel. A lower serum osmolality in HS with respect to normal controls suggests alterations during reticulocyte remodeling. The decreased AQP1 expression could contribute to explain variable degrees of anemia in hereditary spherocytosis. The finding of AQP1 expression induced by Epo in a model of erythroid cells may be interpreted as a mechanism to restore the balance of red cell water fluxes.
Assuntos
Aquaporina 1/biossíntese , Eritrócitos/metabolismo , Regulação da Expressão Gênica , Esferocitose Hereditária/sangue , Adolescente , Adulto , Anemia Hemolítica Autoimune/sangue , Anemia Hemolítica Autoimune/genética , Aquaporina 1/sangue , Aquaporina 1/genética , Transporte Biológico , Água Corporal , Linhagem Celular , Criança , Pré-Escolar , Membrana Eritrocítica/metabolismo , Eritrócitos/patologia , Eritropoetina/farmacologia , Hemólise , Heterozigoto , Humanos , Leucemia Linfocítica Crônica de Células B/sangue , Pessoa de Meia-Idade , Concentração Osmolar , Fragilidade Osmótica , Esferocitose Hereditária/genética , Esferocitose Hereditária/cirurgia , EsplenectomiaRESUMO
Patients with Gaucher type 1 (GD1) throughout Argentina were enrolled in the Argentine bone project to evaluate bone disease and its determinants. We focused on presence and predictors of bone lesions (BL) and their relationship to therapeutic goals (TG) with timing and dose of enzyme replacement therapy (ERT). A total of 124 patients on ERT were enrolled in a multi-center study. All six TG were achieved by 82% of patients: 70.1% for bone pain and 91.1% for bone crisis. However, despite the fact that bone TGs were achieved, residual bone disease was present in 108 patients on ERT (87%) at time 0. 16% of patients showed new irreversible BL (bone infarcts and avascular osteonecrosis) despite ERT, suggesting that they appeared during ERT or were not detected at the moment of diagnosis. We observed 5 prognostic factors that predicted a higher probability of being free of bone disease: optimal ERT compliance; early diagnosis; timely initiation of therapy; ERT initiation dose ≥45 UI/kg/EOW; and the absence of history of splenectomy. Skeletal involvement was classified into 4 major phenotypic groups according to BL: group 1 (12.9%) without BL; group 2 (28.2%) with reversible BL; group 3 (41.9%) with reversible BL and irreversible chronic BL; and group 4 (16.9%) with acute irreversible BL. Our study identifies prognostic factors for achieving best therapeutic outcomes, introduces new risk stratification for patients and suggests the need for a redefinition of bone TG. Am. J. Hematol. 91:E448-E453, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Doenças Ósseas/diagnóstico , Doença de Gaucher/complicações , Adolescente , Adulto , Idoso , Argentina , Doenças Ósseas/etiologia , Doenças Ósseas/patologia , Criança , Diagnóstico Precoce , Terapia de Reposição de Enzimas , Doença de Gaucher/diagnóstico , Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/epidemiologia , Humanos , Adesão à Medicação , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Medição de Risco , Esplenectomia , Adulto Jovem , beta-Glucosidase/uso terapêuticoRESUMO
We studied 31 children with hemolytic anemia, or with positive family history for hereditary spherocytosis (HS), to assess the reliability of capillary blood samples for the diagnosis. HS was diagnosed in 20 patients. Cryohemolysis (CH) was positive in 94% and eosin-5'-maleimide flow cytometry in 90% of them, whereas flow cytometric osmotic fragility was positive in 94%. Capillary blood sampling showed to be useful for the diagnosis. Simultaneous use of these three tests allows confirming diagnosis in 100% of patients. The use of very small blood volumes (300 µl) allows an earlier diagnosis in neonates and small infants.
Assuntos
Anemia Hemolítica/diagnóstico , Coleta de Amostras Sanguíneas/métodos , Esferocitose Hereditária/diagnóstico , Anemia Hemolítica/terapia , Capilares , Criança , Pré-Escolar , Resinas Compostas , Amarelo de Eosina-(YS)/análogos & derivados , Congelamento , Testes Hematológicos/métodos , Hemólise , Humanos , Lactente , Recém-Nascido , Fragilidade Osmótica , Sensibilidade e Especificidade , Esferocitose Hereditária/terapiaRESUMO
BACKGROUND: Primary immune thrombocytopenia is a bleeding diathesis with an unknown etiology in predisposed individuals with immune disturbances. Although it is claimed that children and adults differ in clinical and laboratory aspects, few data exist to corroborate this observation. Our objective was to assess comparative data from children and adults with newly diagnosed immune thrombocytopenia. DESIGN AND METHODS: Clinical and laboratory data of 1,784 children and 340 adults were extracted from the Pediatric and Adult Registry on Chronic Immune Thrombocytopenia. The registry represents a prospective cohort of children and adults with newly diagnosed immune thrombocytopenia. Participating investigators registered their patients immediately after the diagnosis using a web based data transfer. Children aged under 16 years were compared with adults aged 16 years and over with descriptive statistical analyses. RESULTS: The presenting mean platelet count of children and adults was 18.1 and 25.4 × 10(9)/L. Signs of bleeding were reported in 24% of children and in 23% of adults, and intracranial hemorrhage in 10 of 1,784 children and in 6 of 340 adults. Co-morbidity was observed in 3.9% of children and in 30% of adults. Bone marrow aspiration and laboratory tests (antinuclear antibodies, human immunodeficiency and hepatitis C virus) were performed more frequently in adults. Children and adults were followed with a 'watch and wait' strategy in 20% and in 29%, respectively. Immunoglobulins were used more frequently in children and corticosteroids in adults. CONCLUSIONS: Comparative data of children and adults with newly diagnosed immune thrombocytopenia revealed similarities in presenting platelet counts and in bleeding, whereas differences occurred in co-morbidity, diagnostic procedures and therapy.
Assuntos
Púrpura Trombocitopênica Idiopática , Sistema de Registros , Adolescente , Corticosteroides/administração & dosagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulinas/administração & dosagem , Lactente , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/mortalidadeRESUMO
This prospective study was carried out to assess the usefulness of five laboratory tests in the diagnosis of hereditary spherocytosis (HS), based on the correlation of erythrocyte membrane protein defects with clinical and laboratory features, and also to determine the membrane protein deficiencies detected in Argentina. Of 116 patients and their family members tested, 62 of them were diagnosed to have HS. The specificity of cryohemolysis (CH) test was 95.2%, and its cut-off value to distinguish HS from normal was 2.8%. For flow cytometry, cut-off points of 17% for mean channel fluorescence (MCF) decrease and 14% coefficient of variation (CV) increase showed 95.9% and 92.2% specificity, respectively. Both tests showed the highest percentages of positive results for diagnosis. Either CH or flow cytometry was positive in 93.5% of patients. In eight patients, flow cytometry was positive only through CV increase. Protein defects were detected in 72.3% of patients; ankyrin and spectrin were the most frequently found deficiencies. The CV of the fluorescence showed significantly higher increases in moderate and severe anemia than in mild anemia (p = 0.003). Severity of anemia showed no other correlation with tests results, type of deficient protein, inheritance pattern, or neonatal jaundice. CH and flow cytometry are easy methods with the highest diagnostic accuracy. Simultaneous reading of mean channel fluorescence (MCF) decrease and CV increase improve diagnostic usefulness of flow cytometry. This test seems to be a reliable predictor of severity. The type of detected protein deficiency has no predictive value for outcome. Predominant ankyrin and spectrin deficiencies agree with reports from other Latin American countries.
Assuntos
Técnicas de Laboratório Clínico , Testes Hematológicos/métodos , Esferocitose Hereditária/diagnóstico , Adolescente , Adulto , Idoso , Argentina , Criança , Pré-Escolar , Técnicas de Laboratório Clínico/normas , Eletroforese em Gel de Poliacrilamida/métodos , Família , Citometria de Fluxo , Hemólise/fisiologia , Humanos , Lactente , Recém-Nascido , Maleimidas , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Esferocitose Hereditária/sangue , Adulto JovemAssuntos
Eriptose , Eritrócitos/patologia , Febre/complicações , Esferocitose Hereditária/complicações , Esferocitose Hereditária/patologia , Cálcio/metabolismo , Eritrócitos/metabolismo , Febre/sangue , Febre/metabolismo , Febre/patologia , Humanos , Fosfatidilserinas/metabolismo , Esferocitose Hereditária/sangue , Esferocitose Hereditária/metabolismoRESUMO
Non-immune thrombocytopenia is caused by multiple pathologies; the most common causes are extra- or intrauterine infections, whereas secondary cases result from other pathologies involved in the fetal-placentalmaternal interface. This second article lists its causes and provides details of the different pathologies. Platelet transfusion is widely used in neonatology, both as treatment and as bleeding prophylaxis. However, there is no general consensus about the platelet count threshold that is convenient to indicate a transfusion or actual indications. Recent articles are commented regarding the different proposed strategies. The emphasis is on discussing the multiple adverse effects of platelet transfusions because knowledge about them is changing the paradigm for indications, suggesting that a much more restrictive policy is required.
Las trombocitopenias de causa no inmunológica son ocasionadas por múltiples patologías; las más frecuentes son las debidas a infecciones extra- o intrauterinas y las secundarias a otras patologías involucradas en la interrelación niño-placenta-madre. En este segundo artículo, se enumeran sus causas y se describen en detalle las distintas patologías. La transfusión de plaquetas es ampliamente utilizada en neonatología, tanto para tratamiento como para profilaxis de hemorragias. Sin embargo, no hay aún consenso generalizado sobre el umbral de recuento plaquetario conveniente para indicar la transfusión ni sobre sus reales indicaciones. Se comentan artículos recientes sobre las distintas estrategias propuestas. Se enfatiza la discusión sobre los múltiples efectos adversos de las transfusiones de plaquetas, cuyo conocimiento está cambiando el paradigma relativo a sus indicaciones, lo que sugiere que se debe aplicar una política mucho más restrictiva al respecto.
Assuntos
Neonatologia , Trombocitopenia Neonatal Aloimune , Hemorragia , Humanos , Recém-Nascido , Contagem de Plaquetas , Transfusão de Plaquetas , Trombocitopenia Neonatal Aloimune/diagnóstico , Trombocitopenia Neonatal Aloimune/terapiaRESUMO
Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm newborns. Its causes are multiple: it may be due both to pediatric conditions and to other factors involved in the fetal-placental-maternal interface. This initial article describes the causes of thrombocytopenia, proposes a diagnostic approach to manage a thrombocytopenic newborn infant, and provides a detailed description of the different conditions corresponding to thrombocytopenia of immune etiology. It also describes the different causative mechanisms and reviews the varying characteristics of thrombocytopenia secondary to maternal immune thrombocytopenia and neonatal alloimmune thrombocytopenia. The different treatment approaches to each of the different conditions are described both for their pre- as well as their postnatal management. The severity of thrombocytopenia and the serious complications and sequelae associated with the neonatal alloimmune thrombocytopenia are highlighted.
La trombocitopenia, definida como recuento plaquetario inferior a 100 x 109/l, es un hallazgo muy frecuente en el período neonatal, que ocurre, en especial, en niños críticamente enfermos y en prematuros. Sus causas son múltiples: puede deberse tanto a enfermedades del niño como a otros factores involucrados en la interrelación niño-placenta-madre. En este primer artículo, se enumeran las causas de trombocitopenia; se plantea el enfoque diagnóstico frente a un neonato trombocitopénico y se describen detalladamente las distintas entidades correspondientes a trombocitopenias de etiología inmune. Se presentan los diferentes mecanismos causales y se revisan las distintas características de la trombocitopenia secundaria a trombocitopenia inmune materna y de la trombocitopenia neonatal aloinmune. Se describen las diversas estrategias terapéuticas disponibles para cada una de ellas, tanto para su manejo posnatal como para el prenatal. Se enfatiza sobre la gravedad de la enfermedad y las serias complicaciones y secuelas asociadas a la trombocitopenia neonatal aloinmune.
Assuntos
Púrpura Trombocitopênica Idiopática , Trombocitopenia Neonatal Aloimune , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Recém-Nascido , Placenta , Contagem de Plaquetas , Gravidez , Púrpura Trombocitopênica Idiopática/diagnóstico , Trombocitopenia Neonatal Aloimune/diagnóstico , Trombocitopenia Neonatal Aloimune/etiologia , Trombocitopenia Neonatal Aloimune/terapiaRESUMO
Immune thrombocytopenia (ITP) is a common disorder in children and adults. In a patient with newly diagnosed ITP, the treatment strategy is relatively well defined. Second-line treatments are more controversial, and the management of chronic ITP is even more so. During the 3rd ICIS Expert Meeting on Consensus and Development of Strategies in ITP, held in Basel on September 3-5, 2009, a group of experts were tasked with reaching a consensus on some frequently asked questions relating to diagnosis and management of children and adults with chronic ITP. The content of this article is designed to provide a practical support to trained haematologists in their care of patients with chronic ITP.
Assuntos
Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Adulto , Antígenos de Plaquetas Humanas/imunologia , Autoimunidade , Medula Óssea/imunologia , Medula Óssea/fisiopatologia , Criança , Doença Crônica , Humanos , Púrpura Trombocitopênica Idiopática/imunologia , Púrpura Trombocitopênica Idiopática/fisiopatologiaRESUMO
BACKGROUND: Demographics, outcome, and management of idiopathic thrombocytopenic purpura (ITP) in children present differences between countries. Although several factors influence outcome, it is impossible to predict at diagnosis which patients will have acute or chronic disease. High rates of spontaneous remission in chronic ITP have been reported. PROCEDURE: Data concerning 1,683 patients with ITP diagnosed from 1981 to date are presented; outcome was evaluated in 1,418 children. RESULTS: Remarkable presenting features were an incidence peak in the first 2 years of age and male predominance in patients <24 months of age. Three age groups with different recovery rates (P < 0.001) were established (2-12 months: 89.8%; 1-8 years: 71.3%; 9-18 years: 49.0%). Platelet count <10 x 10(9)/L and history of previous illness were associated with higher remission rates only in patients >12 months of age. The score developed by the NOPHO Group showed a predictive value of 83.9% for acute ITP. Spontaneous remission between 6 months and 11 years from diagnosis was achieved by 107 of 325 (32.9%) non-splenectomized children with chronic ITP, and in 44.9% of them between 6 and 12 months from diagnosis. CONCLUSIONS: Age and score were main prognostic factors. Infants <1 year of age are a special group with a brief course and very high recovery rate that are not influenced by other prognostic factors. Definition of groups based on age and scoring could be useful to establish differential management guidelines. The cut-off value to define chronic ITP should be changed to 12 months.
Assuntos
Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/fisiopatologia , Adolescente , Distribuição por Idade , Argentina/epidemiologia , Criança , Pré-Escolar , Demografia , Feminino , Humanos , Incidência , Lactente , Masculino , Prognóstico , Distribuição por SexoRESUMO
Management, outcome, diagnosis, prognosis and treatment of immune thrombocytopenia are controversial. Several guidelines stating different experts' opinions have been published; however, no worldwide consensus regarding the management of the disease has still been reached. This guideline defines diagnostic criteria, states initial laboratory tests, establishes differential diagnosis, develops topics concerning outcome and prognosis, and enumerates available treatments for acute and chronic disease, as well as for management of life-threatening bleeding.
El manejo de la trombocitopenia inmune es motivo de discusión en lo concerniente a evolución, diagnóstico, pronóstico y tratamiento. Se han publicado varias guías que expresan distintas opiniones de expertos, pero no existe aún consenso mundial sobre cuál es el manejo más adecuado de la enfermedad. Esta guía establece los criterios para definir el diagnóstico; detalla el plan de estudios de laboratorio por realizar inicialmente; plantea los distintos diagnósticos diferenciales; desarrolla aspectos relativos a evolución y pronóstico, y enumera los tratamientos disponibles para las formas agudas y las crónicas, así como para el manejo de las emergencias y en algunas situaciones especiales.
Assuntos
Hemorragia/etiologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Doença Aguda , Doença Crônica , Diagnóstico Diferencial , Hemorragia/terapia , Humanos , Prognóstico , Púrpura Trombocitopênica Idiopática/fisiopatologia , Púrpura Trombocitopênica Idiopática/terapiaRESUMO
Recombinant human erythropoietin (rHuEpo) has become the most widely used cytokine in the world. Following the success of its use in patients with end-stage renal disease, the usefulness of rHuEpo to ameliorate other anemias was assessed, including pediatric patients and newborn infants. The treatment or prevention of anemia of prematurity with rHuEpo resulted in a significant reduction in the number of transfusions and donor exposure. A clear definition of which premature babies must receive therapy needs yet to be established. Other indications in neonatal period include hyporegenerative and hemolytic anemias. With the exception of chronic renal failure, in older children the efficacy of rHuEpo has not been evaluated as in adults. While an impressive amount of studies were carried out during the last years in adult patients with cancer-related or HIV-infection-related anemias, allowing to establish clear conclusions on its efficacy, only a few trials with small number of patients have been reported in children. Up to date, results in pediatric patients suggest that rHuEpo therapy is as useful as in adult patients, but prospective, randomized trials including large number of patients are essential to achieve definitive conclusions. Results of studies designed to evaluate the efficacy of rHuEpo for sustaining an adequate dose of ribavirin in patients receiving treatment for hepatitis C are encouraging. The potential for use of the non-hematopoietic effects of rHuEpo in newborn infants is a novel and exciting issue. The role of rHuEpo as a tissue protective factor for central nervous system and intestinal mucosa is under exhaustive investigation.
Assuntos
Anemia/tratamento farmacológico , Eritropoetina/uso terapêutico , Insuficiência Renal/tratamento farmacológico , Adulto , Anemia/etiologia , Anemia Neonatal/tratamento farmacológico , Criança , Pré-Escolar , Eritropoetina/efeitos adversos , Infecções por HIV/complicações , Hepatite C/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Criança Pós-Termo , Neoplasias/complicações , Proteínas Recombinantes , Diálise Renal , Insuficiência Renal/complicaçõesRESUMO
Las trombocitopenias de causa no inmunológica son ocasionadas por múltiples patologías; las más frecuentes son las debidas a infecciones extra- o intrauterinas y las secundarias a otras patologías involucradas en la interrelación niño-placenta-madre. En este segundo artículo, se enumeran sus causas y se describen en detalle las distintas patologías. La transfusión de plaquetas es ampliamente utilizada en neonatología, tanto para tratamiento como para profilaxis de hemorragias. Sin embargo, no hay aún consenso generalizado sobre el umbral de recuento plaquetario conveniente para indicar la transfusión ni sobre sus reales indicaciones. Se comentan artículos recientes sobre las distintas estrategias propuestas. Se enfatiza la discusión sobre los múltiples efectos adversos de las transfusiones de plaquetas, cuyo conocimiento está cambiando el paradigma relativo a sus indicaciones, lo que sugiere que se debe aplicar una política mucho más restrictiva al respect
Non-immune thrombocytopenia is caused by multiple pathologies; the most common causes are extra- or intrauterine infections, whereas secondary cases result from other pathologies involved in the fetal-placental-maternal interface. This second article lists its causes and provides details of the different pathologies. Platelet transfusion is widely used in neonatology, both as treatment and as bleeding prophylaxis. However, there is no general consensus about the platelet count threshold that is convenient to indicate a transfusion or actual indications. Recent articles are commented regarding the different proposed strategies. The emphasis is on discussing the multiple adverse effects of platelet transfusions because knowledge about them is changing the paradigm for indications, suggesting that a much more restrictive policy is required
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Trombocitopenia/etiologia , Trombocitopenia/patologia , Transfusão de Plaquetas/efeitos adversos , HemorragiaRESUMO
La trombocitopenia, definida como recuento plaquetario inferior a 100 x 109/l, es un hallazgo muy frecuente en el período neonatal, que ocurre, en especial, en niños críticamente enfermos y en prematuros. Sus causas son múltiples: puede deberse tanto a enfermedades del niño como a otros factores involucrados en la interrelación niño-placenta-madre. En este primer artículo, se enumeran las causas de trombocitopenia; se plantea el enfoque diagnóstico frente a un neonato trombocitopénico y se describen detalladamente las distintas entidades correspondientes a trombocitopenias de etiología inmune. Se presentan los diferentes mecanismos causales y se revisan las distintas características de la trombocitopenia secundaria a trombocitopenia inmune materna y de la trombocitopenia neonatal aloinmune. Se describen las diversas estrategias terapéuticas disponibles para cada una de ellas, tanto para su manejo posnatal como para el prenatal. Se enfatiza sobre la gravedad de la enfermedad y las serias complicaciones y secuelas asociadas a la trombocitopenia neonatal aloinmune
Thrombocytopenia, defined as a platelet count below 100 x 109/L, is a very common finding in the neonatal period, especially in critically ill infants and preterm newborns. Its causes are multiple: it may be due both to pediatric conditions and to other factors involved in the fetal-placental-maternal interface. This initial article describes the causes of thrombocytopenia, proposes a diagnostic approach to manage a thrombocytopenic newborn infant, and provides a detailed description of the different conditions corresponding to thrombocytopenia of immune etiology. It also describes the different causative mechanisms and reviews the varying characteristics of thrombocytopenia secondary to maternal immune thrombocytopenia and neonatal alloimmune thrombocytopenia. The different treatment approaches to each of the different conditions are described both for their pre- as well as their postnatal management. The severity of thrombocytopenia and the serious complications and sequelae associated with the neonatal alloimmune thrombocytopenia are highlighted.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Trombocitopenia Neonatal Aloimune/etiologia , Trombocitopenia Neonatal Aloimune/terapia , Imunoglobulina G/uso terapêutico , Transfusão de Plaquetas , Diagnóstico Diferencial , Trombocitopenia Neonatal Aloimune/diagnóstico , HemorragiaRESUMO
The incidence of thrombosis is higher among newborn infants than in any other stage of pediatric development. This fact is the consequence of labile characteristics of the neonatal hemostatic system, in addition to exposure to multiple risk factors and the wide use of vascular catheters. Venous thromboses, which mainly affect the limbs, the right atrium and renal veins, are more frequently seen than arterial thromboses. A stroke may be caused by the occlusion of the arterial flow entering the brain or by occlusion of its venous drainage system. Purpura fulminans is a very severe condition that should be treated as a medical emergency, and is secondary to severe protein C deficiency or, less frequently, protein S or antithrombin deficiency. Most thrombotic events should be managed with antithrombotic therapy, which is done with unfractionated and/or low molecular weight heparins. Purpura fulminans requires protein C replacement and/or fresh frozen plasma infusion. Thrombolytic therapy is done using tissue plasminogen activator and should only be used for life-, or limb-, or organ-threatening thrombosis.
La probabilidad de padecer trombosis es mucho mayor en el período neonatal que en cualquier otra etapa pediátrica. La labilidad del particular sistema hemostático del neonato, sumada a los múltiples factores de riesgo a que está expuesto y la presencia casi constante de catéteres, son responsables de este hecho. Las trombosis venosas son más frecuentes que las arteriales y ocurren principalmente en los miembros, la aurícula derecha y las venas renales. El accidente cerebrovascular puede ser causado por la oclusión del flujo arterial que llega al cerebro o del sistema de drenaje venoso de este. La púrpura fulminans es una patología de altísima gravedad, que debe ser considerada una emergencia médica y se debe a la deficiencia grave de proteína C o, menos frecuentemente, de proteína S o antitrombina. La mayoría de los episodios trombóticos tienen indicación de tratamiento anticoagulante, que se puede realizar con heparina no fraccionada y/o con heparina de bajo peso molecular. La púrpura fulminans requiere terapia de sustitución con proteína C y/o plasma fresco. El tratamiento trombolítico se realiza con activador tisular del plasminógeno y debe quedar reservado solo para aquellas trombosis cuya localización implique compromiso de vida o pérdida de un órgano o de un miembro.
Assuntos
Doenças do Recém-Nascido/epidemiologia , Trombose/epidemiologia , Humanos , Recém-Nascido , Deficiência de Proteína C/epidemiologia , Púrpura Fulminante/epidemiologia , Fatores de Risco , Trombose Venosa/epidemiologiaRESUMO
Hereditary spherocytosis must always be suspected in children with anemia, hyperbilirubinemia, splenomegaly or cholelithiasis, in the asymptomatic individual with an affected relative, and in the neonate with hyperbilirubinemia with no blood group incompatibility; its early detection is key to avoid kernicterus. Follow-up of these patients is based on periodical control and supply of information on the adequate management of hemolytic or aplastic crisis, and early detection of cholelithiasis. The decision to perform splenectomy is usually associated with quality of life rather than life-threatening risk, and it should result from a consensus between patient, parents and physicians. The postsplenectomy follow-up is based on control of compliance with the prophylactic antibiotic therapy and the early diagnosis of infectious disorders.
Assuntos
Esferocitose Hereditária , Adolescente , Criança , Pré-Escolar , Humanos , Esferocitose Hereditária/complicações , Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/terapia , Esplenectomia , Resultado do TratamentoRESUMO
Hereditary spherocytosis is the most frequent hereditary anemia excluding beta thalassemia in Argentina. Historical, demographic, genetic and pathogenic aspects of the disease are reviewed, and confirmatory laboratory tests are described. Special characteristics on the outcome of the disease in our population and prevalent protein deficiencies in our country are described. Emphasis is given on new available laboratory tests, which allow an earlier diagnosis using volume of blood samples significantly smaller than required for conventional tests.
Assuntos
Esferocitose Hereditária , Demografia , História do Século XIX , História do Século XX , Humanos , Esferocitose Hereditária/diagnóstico , Esferocitose Hereditária/epidemiologia , Esferocitose Hereditária/etiologia , Esferocitose Hereditária/históriaRESUMO
Los objetivos del presente estudio fueron: a) Analizar las características demográficas y clínicas de nuestra población al diagnóstico; b) Evaluar si las pruebas más recientes presentan ventajas sobre las tradicionales; c) Confirmar la frecuencia de las distintas deficiencias de proteínas de membrana; d) Establecer la relación entre severidad y resultado de las pruebas o tipo de deficiencia. Se analizaron 359 individuos estudiados desde 2007, cuando se incorporaron criohemólisis hipertónica (CH), citometría de flujo con eosina-5'- maleimida (5'EMA-CF), FOE por citometría de flujo (FOE-CF) y electroforesis de proteínas de membrana (SDS-PAGE) al estudio de laboratorio clásico, fragilidad osmótica eritrocitaria (FOE) y autohemólisis (AH). Criterios diagnósticos para Esferocitosis Hereditaria (ESH): esferocitos en frotis y dos pruebas positivas. Se identificaron 174 pacientes con ESH y 22 portadores sanos. El 74,9% eran menores de 12 años. La transmisión fue dominante en el 83,1% de los casos. Tuvieron manifestaciones neonatales 89,1%. Las pruebas con mayor sensibilidad fueron CH (92,0%), FOE diferida (91,1%) y 5'EMA-CF (88,5%). En los 125 pacientes en quienes se realizaron CH, 5'EMA-CF y FOE-CF se observó que todos tenían al menos una prueba positiva; 122 (97,6%) tuvieron dos o tres positivas. Las deficiencias más frecuentes fueron ankirina y espectrina. No hubo diferencia en el resultado de las pruebas entre los subgrupos de severidad. Se concluye que las deficiencias más frecuentes en Argentina son ankirina y espectrina, coincidiendo con otras poblaciones latinoamericanas. El uso simultáneo de CH, 5'EMA-CF y FOE-CF permite diagnosticar más del 97% de los casos. La incidencia de manifestaciones neonatales es elevada.
The aims of this study were (a) to assess demographic and clinical aspects of our population at diagnosis; (b) to evaluate diagnostic accuracy of hypertonic cryohemolysis (HC), eosin-5'-maleimide flow cytometry (EMA-FC) and flow cytometric osmotic fragility (OF-FC) in relation to standard screening tests osmotic fragility (OF) and autohemolysis (AH); (c) to confirm the previously reported prevalence of membrane proteins defects; and (d) to assess the relationship between severity of anemia and results of confirmatory tests. Since 2007, the following tests were available in our laboratory: OF, AH, HC, EMA-FC, OF-FC and SDS-PAGE of membrane proteins. Diagnostic criteria for hereditary spherocytosis were spherocytes in blood smear plus ≥2 positive tests. Data from 359 individuals were analyzed: 174 HS patients and 22 silent carriers were detected; 74.9% of patients were less than 12 years old; 83.1% of them showed a dominant inheritance pattern; antecedent of neonatal jaundice/anemia was registered in 89.1%. Tests with higher sensitivity were: HC (92.0%), incubated OF (91.1%), and EMA-FC (88.5%). HC, EMA-FC and OF-FC were simultaneously performed on 125 patients: each of them had at least 1 positive test; 122 (97.6%) had 2 or 3 positive tests. Ankyrin and spectrin were the most frequently found protein deficiencies. Comparison of test results in relation to severity of anemia showed no difference between groups. It can be concluded that compared toother Latin American countries, ankyrin and spectrin were the most frequent protein deficiencies. Simultaneous performing of HC, EMA-FC and OF-FC enabled diagnosing HS in more than 97% of patients. A high incidence of neonatal jaundice/anemia was observed.
Os objetivos do presente estudo foram: a) analisar as características demográficas e clínicas de nossa população ao diagnóstico; b) Avaliar se as provas mais recentes apresentam vantagens sobre as tradicionais; c) Confirmar a frequência das diversas deficiências de proteínas de membrana; d) Establecer a relação entre severidade e resultado das provas ou tipo de deficiência. Foram analisados 359 indivíduos estudados desde 2007, quando se incorporaram crio-hemólise hipertônica (CH), citometria de fluxo com eosina-5'-maleimida (5'EMA-CF), FOE por citometria de fluxo (FOE-CF) e eletroforese de proteínas de membrana (SDS-PAGE) ao estudo de laboratório clássico - fragilidade osmótica eritrocitária (FOE) e auto-hemólise (AH). Critérios diagnósticos para ESH: esferócitos em esfregaço e duas provas positivas. Foram identificados 174 pacientes com ESH e 22 portadores sadios. 74,9% eram menores de 12 anos. A transmissão foi dominante em 83,1%. Tiveram manifestações neonatais 89,1%. As provas com maior sensibilidade foram CH (92,0%), FOE diferida (91,1%) e 5'EMA-CF (88,5%). Nos 125 pacientes aos quais lhes realizaram CH, 5'EMA-CF e FOE-CF se observou que todos tinham no mínimo uma prova positiva; 122 (97,6%) tiveram duas ou três positivas. As deficiências mais frequentes foram anquirina e espectrina. Não houve diferença no resultado das provas entre os subgrupos de severidade. Conclui-se que as deficiências mais frequentes na Argentina são anquirina e espectrina, as quais coincidem com outras populações latinoamericanas. O uso simultâneo de CH, 5'EMA-CF e FOE-CF permite diagnosticar mais de 97% dos casos. A incidência de manifestações neonatais é elevada.
Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Esferocitose Hereditária , Eritrócitos , Anemia Hemolítica , Argentina , Proteína 1 de Troca de Ânion do EritrócitoRESUMO
La probabilidad de padecer trombosis es mucho mayor en el período neonatal que en cualquier otra etapa pediátrica. La labilidad del particular sistema hemostático del neonato, sumada a los múltiples factores de riesgo a que está expuesto y la presencia casi constante de catéteres, son responsables de este hecho. Las trombosis venosas son más frecuentes que las arteriales y ocurren principalmente en los miembros, la aurícula derecha y las venas renales. El accidente cerebrovascular puede ser causado por la oclusión del flujo arterial que llega al cerebro o del sistema de drenaje venoso de este. La púrpura fulminans es una patología de altísima gravedad, que debe ser considerada una emergencia médica y se debe a la deficiencia grave de proteína C o, menos frecuentemente, de proteína S o antitrombina. La mayoría de los episodios trombóticos tienen indicación de tratamiento anticoagulante, que se puede realizar con heparina no fraccionada y/o con heparina de bajo peso molecular. La púrpura fulminans requiere terapia de sustitución con proteína C y/o plasma fresco. El tratamiento trombolítico se realiza con activador tisular del plasminógeno y debe quedar reservado solo para aquellas trombosis cuya localización implique compromiso de vida o pérdida de un órgano o de un miembro.
The incidence of thrombosis is higher among newborn infants than in any other stage of pediatric development. This fact is the consequence of labile characteristics of the neonatal hemostatic system, in addition to exposure to multiple risk factors and the wide use of vascular catheters. Venous thromboses, which mainly affect the limbs, the right atrium and renal veins, are more frequently seen than arterial thromboses. A stroke may be caused by the occlusion of the arterial flow entering the brain or by occlusion of its venous drainage system. Purpura fulminans is a very severe condition that should be treated as a medical emergency, and is secondary to severe protein C deficiency or, less frequently, protein S or antithrombin deficiency. Most thrombotic events should be managed with antithrombotic therapy, which is done with unfractionated and/or low molecular weight heparins. Purpura fulminans requires protein C replacement and/or fresh frozen plasma infusion. Thrombolytic therapy is done using tissue plasminogen activator and should only be used for life-, or limb-, or organ-threatening thrombosis.