[Guideline for diagnosis and treatment of immune thrombocytopenia]. / Trombocitopenia inmune. Guía de diagnóstico y tratamiento.

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.

Skeletal involvement in Gaucher disease: An observational multicenter study of prognostic factors in the Argentine Gaucher disease patients.

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.

Thrombosis in newborn infants.

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.

Trombosis en el recién nacido / Thrombosis in newborn infants

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.

[Recombinant erythropoietin as treatment for hyporegenerative anemia following hemolytic disease of the newborn]. / Tratamiento de la anemia hiporregenerativa tardía de la enfermedad hemolítica del recién nacido con eritropoyetina recombinante.

INTRODUCTION: The aim of the study is to report results of erythropoietin treatment for late hyporegenerative anemia in the hemolytic disease of the newborn (HDN). Reports previously published concern only a few cases, with controversial results. METHODS: Case series report concerning 50 neonates with HDN due to Rh, ABO or KpA antigens, aged more than 7 days. Erythropoietin treatment started when hematocrit dropped to levels requiring transfusion, with an inappropriate reticulocyte response (Reticulocyte Production Index <1). RESULTS: At start of treatment mean age was 24.3 +/- 12.0 days (range 8-65 days), hematocrit 24.1 +/- 2.8% (range 18-30%), and Reticulocyte Production Index 0.34 +/- 0.25 (range 0.05-0.98). Hematocrit and Reticulocyte Production Index showed significant increases after 7 and 14 days of treatment (p <0.001). No difference was observed either between infants with Rh-HDN and ABO-HDN or between Rh-HDN patients with or without intrauterine transfusions. Seven infants (14%) required one packed RBC transfusion during erythropoietin therapy, 2 of them within 72 hours from starting treatment. The percentage of transfused infants showed no difference either between ABO-HDN and Rh-HDN or between Rh-HDN with and without intrauterine transfusions. Moderate, short-lasting neutropenia, not associated to infections, was observed in 11 patients. No other adverse effect was observed. CONCLUSIONS: The administration of erythropoietin appears to be a safe and useful therapy. Its efficacy should be confirmed by randomized studies.

Tratamiento de la anemia hiporregenerativa tardía de la enfermedad hemolítica del recién nacido con eritropoyetina recombinante / Recombinant erythropoietin as treatment for hyporegenerative anemia following hemolytic disease of the newborn

Introducción. La experiencia previamente publicada sobre el tema se limita a pocos casos, con resultadoscontrovertidos. Objetivo. Comunicar los resultados del tratamiento con eritropoyetina en la anemia hiporregenerativa tardía de la enfermedad hemolítica del recién nacido (EHRN). Población, material y métodos. Estudio observacional prospectivo sobre 50 neonatos mayores de 7 días con EHRN secundaria a incompatibilidadesRh, ABO o KpA. Se comenzó tratamiento con eritropoyetina cuando el hematócrito descendía a valores que requerían transfusión, acompañado de una respuesta reticulocitaria inadecuada (Indice de Producción Reticulocitaria <1). Resultados. Al comienzo del tratamiento la edad fue 24,3 ± 12,0 días (intervalo 8-65 días), el hematócrito24,1 ± 2,8% (intervalo 18-30%) y el Índice de Producción Reticulocitaria 0,34 ± 0,25 (intervalo 0,05-0,98). Se observaron aumentos significativosdel hematócrito y del Indice de Producción Reticulocitaria a los 7 y 14 días de tratamiento (p <0,001). No hubo diferencias entre los niños con EHRN-Rh y con EHRN-ABO, o entre los pacientes con EHRNRh que habían recibido o no transfusiones intrauterinas.Durante el tratamiento con eritropoyetina fueron transfundidos 7 niños (14%), 2 de ellos durante las primeras 72 h de su comienzo. No hubodiferencias en el porcentaje de pacientes transfundidos entre aquellos con EHRN-Rh o con EHRNABO, o entre los pacientes con EHRN-Rh que habíanrecibido o no transfusiones intrauterinas. Se observó neutropenia moderada de corta duración, no asociada a infecciones, en 11 pacientes. No se registró ningún otro efecto adverso. Conclusiones. La eritropoyetina parece ser un tratamiento útil y seguro. Su eficacia deberá ser confirmada por futuros estudios aleatorizados.

Introduction. The aim of the study is to report results of erythropoietin treatment for late hyporegenerativeanemia in the hemolytic disease of thenewborn (HDN). Reports previously published concern only a few cases, with controversial results. Methods. Case series report concerning 50 neonates with HDN due to Rh, ABO or KpA antigens, aged more than 7 days. Erythropoietin treatment started when hematocrit dropped to levels requiring transfusion, with an inappropriate reticulocyte response (Reticulocyte Production Index <1). Results. At start of treatment mean age was 24.3 ± 12.0 days (range 8-65 days), hematocrit 24.1 ± 2.8% (range 18-30%), and Reticulocyte Production Index 0.34 ± 0.25 (range 0.05-0.98). Hematocrit and Reticulocyte Production Index showed significant increases after 7 and 14 days of treatment (p <0.001). No difference was observed either between infantswith Rh-HDN and ABO-HDN or between Rh-HDN patients with or without intrauterine transfusions. Seven infants (14%) required one packed RBC transfusion during erythropoietin therapy, 2 of them within 72 hours from starting treatment. The percentage of transfused infants showed no differenceeither between ABO-HDN and Rh-HDN or between Rh-HDN with and without intrauterine transfusions. Moderate, short-lasting neutropenia, not associatedto infections, was observed in 11 patients. No other adverse effect was observed. Conclusions. The administration of erythropoietin appears to be a safe and useful therapy. Its efficacy should be confirmed by randomized studies.

Demographic data, natural history, and prognostic factors of idiopathic thrombocytopenic purpura in children: a multicentered study from Argentina.

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.