Síndrome de Evans asociada a infección por citomegalovirus en una niña de 13 meses / Evans Syndrome Associated With Cytomegalovirus Infection In A 13-Month-Old Girl

Introducción: El síndrome de Evans es un desorden autoinmune poco frecuente, caracterizado por el descenso de al menos dos líneas celulares hemáticas. Las publicaciones del síndrome de Evans e infección por citomegalovirus resultan escasas. Objetivo: Examinar el caso de una niña con síndrome de Evans e infección activa por citomegalovirus que respondió favorablemente a la terapia antiviral. Presentación del caso: Niña de 13 meses con antecedentes de prematuridad y bajo peso al nacer, que acudió a consulta por presentar palidez y equimosis en tórax, abdomen y extremidades. En los exámenes de laboratorio se encontró trombocitopenia y anemia severa con prueba de Coombs directo positiva. Recibió pulsos de metilprednisolona con respuesta desfavorable. La carga viral resultó positiva para citomegalovirus (4019 copias de ADN) y recibió valganciclovir con evolución favorable en el seguimiento. Conclusiones: El síndrome de Evans asociado a infección por CMV es infrecuente. El tratamiento con valganciclovir podría ser beneficioso para cierto grupo de pacientes; sin embargo, hacen falta más estudios que demuestren la eficacia y seguridad de este tratamiento en este síndrome; más aún si está asociado a una elevada carga viral(AU)

Introduction: Evans syndrome is a rare autoimmune disorder, characterized by the descent of at least two blood cell lines. Publications of Evans syndrome and cytomegalovirus infection are scarce. Objective: To examine the case of a girl with Evans syndrome and active cytomegalovirus infection who responded favorably to antiviral therapy. Case presentation: A 13-month-old girl with a history of prematurity and low birth weight, who attended the consultation for presenting pallor and ecchymosis in the thorax, abdomen and extremities. Laboratory tests found thrombocytopenia and severe anemia after a positive direct Coombs test. She received pulses of methylprednisolone with unfavorable response. The viral load was positive for cytomegalovirus (4019 copies of DNA) and received valganciclovir with favorable evolution at follow-up. Conclusions: Evans syndrome associated with CMV infection is uncommon. Treatment with valganciclovir may be beneficial for a certain group of patients. However, more studies are needed to demonstrate the efficacy and safety of this treatment in this syndrome; even more so if it is associated with a high viral load(AU)

Trombocitopenia neonatal: Revisión. I. Definiciones, diagnóstico diferencial, causas, trombocitopenias inmunes / Neonatal thrombocytopenia: A review. I. Definitions, differential diagnosis, causes, immune thrombocytopenia

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.

Neutropenia aloimune neonatal em gêmeas idênticas / Neonatal alloimmune neutropenia in identical twins

A neutropenia aloimune neonatal (NAN) é uma patologia causada pelo antagonismo imunológico, como a doença hemolítica do recém-nascido ou a trombocitopenia aloimune neonatal, mas relacionada aos neutrófilos, em vez de glóbulos vermelhos ou plaquetas. Descreveremos um caso clínico de duas gêmeas idênticas nascidas a termo, com Apgar de 8 e 9, sendo que após algumas horas do nascimento apresentaram febre. Um exame de sangue revelou neutropenia grave que resultou em sepse. O diagnóstico da NAN foi realizado clinicamente e por testes de histocompatibilidade. A prova cruzada por citometria de fluxo foi positiva, usando soro da mãe e suspensões celulares (granulócitos e linfócitos) das gêmeas e do pai. Este teste não fornece informações sobre para qual sistema genético os anticorpos foram positivos, se contra os antígenos específicos de neutrófilos humanos (HNA) ou contra os antígenos leucocitários humanos (HLA). Para o esclarecimento, realizamos o teste de aglutinação de granulócitos (GAT) com um painel de doadores fidelizados e com antígenos HNA1-5 conhecidos, utilizando o soro materno como reagente. Foi também realizada a pesquisa de anticorpos anti-HLA e anti-HNA no soro materno. Os genótipos HLA e HNA foram identificados, permitindo conhecer as especificidades dos anticorpos maternos contra os antígenos dos neutrófilos do marido e das filhas. O diagnóstico de NAN não é realizado na maioria dos hospitais de nosso país e do exterior, devido à dificuldade de execução dos testes de histocompatibilidade, no entanto a prova cruzada por citometria de fluxo pode facilmente ser implantada nos laboratórios clínicos, sendo que está descrita detalhadamente nesse caso clínico.

Neonatal alloimmune neutropenia (NAN) is a disease caused by immunological antagonism, such as hemolytic disease of the newborn or neonatal alloimmune thrombocytopenia, but related to neutrophils rather than to red blood cells or platelets. We will describe a clinical case of two identical twins born with Apgar 8 and 9 that started with fever few hours after delivery. A blood test revealed severe neutropenia, which was followed by sepsis. The diagnosis of NAN was done clinically and by histocompatibility testing. Flow cytometry crossmatch was positive, using mother serum and cell suspensions (granulocytes and lymphocytes) from the twin girls and from the father. This test did not provide information about the genetic system for which the antibodies are positive, if against human neutrophil antigens (HNA) or human leucocyte antigens (HLA). To clear this, the granulocyte agglutination test (GAT) was performed with a panel of control donors with known HNA1-5 antigens, using the maternal serum as a reagent. We did also a Luminex screening assay for detection of anti-HLA and anti-HNA antibodies in the mother serum. The HLA and HNA genotypes were identified, which allowed to define specificities in mother's antibodies against the neutrophil surface antigens from her husband and from the twins. The diagnosis of NAN diagnose is not done in most hospitals worldwide, mainly by the difficulty in executing the histocompatibility test. However, the crossmatch by flow cytometry could be easily done in clinical laboratories following the method described in this article.

Conocimientos actuales sobre la patogénesis, presentación clínica, diagnóstico y manejo de la trombocitopenia neonatal aloinmune / Current knowledge on neonatal alloimmune thrombocytopenia's pathogenesis, clinical presentation, diagnostic and management

Introducción: La trombocitopenia neonatal aloinmune es una enfermedad producida por anticuerpos maternos contra antígenos plaquetarios fetales heredados del padre. Puede ser causa de hemorragia intracraneal y conducir a la muerte o discapacidad en el feto/neonato. Aunque es la causa más grave de trombocitopenia en el neonato y la más común en los recién nacidos a término, en general ha sido poco investigada. Objetivos: Exponer los conocimientos actuales sobre la patogénesis, presentación clínica, diagnóstico y del manejo pre- y posnatal de la trombocitopenia neonatal aloinmune, Métodos: Se realizó una revisión de la literatura, en inglés y español, a través del sitio web PubMed y el motor de búsqueda Google académico de artículos publicados en los últimos 10 años. Se hizo un análisis y resumen de la bibliografía revisada. Resultados: Los anticuerpos IgG maternos son transportados a través de la placenta a la circulación fetal, opsonizan las plaquetas fetales que son removidas por fagocitosis. Los antígenos más implicados son el HPA-1a y HPA-4a. La fisiopatología de la enfermedad es muy similar a la enfermedad hemolítica perinatal, pero aún no se han implementado programas de pesquisa y el diagnóstico se realiza después del nacimiento del niño afectado de trombocitopenia, hemorragia intracraneal o muerte in útero de causa no explicada. Consideraciones finales: El impacto clínico de la trombocitopenia neonatal aloinmune y las oportunidades de tratamiento potencian la necesidad de implantar programas de pesquisa para la detección de fetos en riesgo de padecer esta enfermedad(AU)

Introduction: Neonatal alloimmune thrombocytopenia is a disease produced by maternal antibodies against fetal platelet antigens inherited from the father. It can be a cause of intracranial hemorrhage and lead to death or disability in the fetus / neonate. Although it is the most serious cause of thrombocytopenia in newborns and the most common in full-term infants, it has generally been poorly investigated. Objectives: To approximate to current knowledge about the pathogenesis, clinical presentation, diagnosis and pre- and post-natal management of neonatal alloimmune thrombocytopenia. Methods: A review of literature, in English and Spanish, through PubMed website and Google scholar search engine of articles published in the last 10 years was conducted. An analysis and summary of the reviewed bibliography was made. Results: Maternal IgG antibodies are transported through the placenta to the fetal circulation, opsonizing fetal platelets that are removed by phagocytosis. The most involved antigens are HPA-1a and HPA-4a. The pathophysiology of this disease is very similar to perinatal hemolytic disease, but research programs have not been implemented yet and diagnosis is made after birth of children affected by thrombocytopenia, intracranial hemorrhage or in uterus death by unexplained causes. Final considerations: Clinical impacts of neonatal alloimmune thrombocytopenia and treatment opportunities enhance the need to implement screening programs for the detection of fetuses at risk of suffering from this disease(AU)

Neonatal Thrombocytopenia: Diagnostic Approach and Platelet Transfusion Guideline / 임상소아혈액종양

Neonatal thrombocytopenia, defined as platelet counts of less than 150,000/µL, is a frequent hematologic abnormality in neonatal period. Differential diagnosis of neonatal thrombocytopenia may be challenging to pediatric hematologists and neonatologists because neonatal thrombocytopenia is associated with diverse maternal or neonatal clinical conditions. An accurate diagnosis for neonatal thrombocytopenia will lead to appropriate evaluation and management. Platelet transfusion is the primary management of neonatal thrombocytopenia. Most thrombocytopenic newborns received platelet concentrates to prevent major hemorrhage or treat ongoing bleeding according to institutional policy. However, scientific evidences for benefit and consistent guideline for platelet transfusion in neonates are lacking, further investigation to establish the standard recommendation for platelet transfusion is needed. This article reviewed the diagnostic approach and current guideline for platelet transfusion management for neonatal thrombocytopenia.

Predictive Factors for Severe Thrombocytopenia and Classification of Causes of Thrombocytopenia in Premature Infants

PURPOSE: This study investigated predictive factors for severe neonatal thrombocytopenia, which greatly increases the need for intensive care and is associated with a high mortality rate in premature infants. Factors adopted for prompt identification of at-risk newborns include blood test results and birth history. This study analyzed the relationship between the presence of severe neonatal thrombocytopenia and the mortality rate. The causes of thrombocytopenia in premature infants were also examined. METHODS: This retrospective study evaluated 625 premature infants admitted to the neonatal intensive care unit (NICU) at Chung-Ang University Medical Center. The neonates were classified into 3 groups according to the severity of thrombocytopenia: mild (100×10⁹/L≤platelet < 150×10⁹/L), moderate (50×10⁹/L≤platelet < 100×10⁹/L), or severe (platelet < 50×10⁹/L). Analysis of blood samples obtained at the onset of thrombocytopenia included platelet count, white blood cell (WBC) count, hemoglobin level, hematocrit level, absolute neutrophil count, and high-sensitivity C-reactive protein level. RESULTS: Of the 625 premature infants admitted to our NICU, 214 were detected with thrombocytopenia. The mortality rate in thrombocytopenic neonates was 18.2% (39/214), whereas a mortality rate of only 1.0% was observed in non-thrombocytopenic neonates. The major causes of thrombocytopenia were perinatal insufficiency and sepsis in premature infants. Severe thrombocytopenia was noted more frequently in premature infants with higher WBC counts and in those with a younger gestational age. CONCLUSION: Platelet count, WBC count, and gestational age are reliable predictors for severe neonatal thrombocytopenia. The major causes of thrombocytopenia were perinatal insufficiency and sepsis in premature infants.

Trombocitopenia na gravidez / Thrombocytopenia in pregnant

A trombocitopenia na mulher grávida é diagnosticada frequentemente pelos obstetras porque a contagem de plaquetas está incluída nos exames de rotina no pré-natal. A trombocitopenia, definida como a contagem de plaquetas inferior a 150.000/mm3, é comum e ocorre em 7-12% das gestações. Algumas causas de trombocitopenia são graves desordens médicas com potencial para morbidade materna e fetal. Ao revés, outras condições, tais como trombocitopenia gestacional, são benignas e não acarretam riscos maternos ou fetais.(AU)

Thrombocytopenia in pregnant women is often diagnosed by obstetricians because platelet count is included in prenatal routine exams. Thrombocytopenia is defined as platelet count below 150,000 / mm3 is common and occurs in 7-12% of pregnancies. Some causes of thrombocytopenia are serious medical disorders with potential for maternal and fetal morbidity. Conversely, other conditions, such as gestational thrombocytopenia, are benign and do not cause maternal or fetal risks.(AU)

Successful management of neonatal alloimmune thrombocytopenia in the second pregnancy: a case report / Sucesso no manejo da trombocitopenia aloimune neonatal na segunda gestação: relato de caso

Neonatal alloimmune thrombocytopenia is a serious disease, in which the mother produces antibodies against fetal platelet antigens inherited from the father; it is still an underdiagnosed disease. This disease is considered the platelet counterpart of the RhD hemolytic disease of the fetus and newborn, yet in neonatal alloimmune thrombocytopenia the first child is affected with fetal and/or neonatal thrombocytopenia. There is a significant risk of intracranial hemorrhage and severe neurological impairment, with a tendency for earlier and more severe thrombocytopenia in subsequent pregnancies. This article reports a case of neonatal alloimmune thrombocytopenia in the second pregnancy affected and discusses diagnosis, management and the clinical importance of this disease.

A púrpura trombocitopênica neonatal aloimune é uma doença grave, na qual a mãe produz anticorpos contra antígenos plaquetários fetais herdados do pai, e é ainda subdiagnosticada na prática clínica. É considerada o equivalente plaquetário da doença hemolítica do recém-nascido, com a diferença que o primeiro filho é afetado, apresentando trombocitopenia fetal e/ou neonatal. Há risco significativo de hemorragia intracraniana e sequelas neurológicas graves, com tendência a trombocitopenia mais grave e mais precoce nas gestações subsequentes. Este artigo relata um caso de trombocitopenia aloimune neonatal na segunda gestação afetada e discute diagnóstico, manejo e importância clínica dessa doença na prática clínica.

Detection, diagnosis and analysis of the first case of neonatal alloimmune thrombocytopenia purpura associated with anti-HPA-5b in China / 中国实验血液学杂志

This study was aimed to investigate the detection and diagnosis of the neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti-HPA-5b antibody. The platelet count and clinical manifestation in the newborn were examined. The HPA-1-21bw genotypes of the newborn and her parents were detected by multiple-PCR and DNA sequencing. The HPA-specific antibody in the sera of newborn and her mother were detected and identified by flow cytometry (FCM) and monoclonal antibody-specific immobilization of platelet antigens (MAIPA). The results indicated that the clinical manifestations of the newborn were lighter. The HPA genotyping showed that the genotype of the newborn was HPA-5ab, while that of her mother and father were HPA-5aa and HPA-5ab, respectively. The antibody against the platelet of newborn's father existed in the newborn's mother sera. The HPA antibody of the mother was identified as anti-HPA-5b. It is concluded that the newborn with neonatal alloimmune thrombocytopenia purpura was caused by the antibody against HPA-5b.

Infección por dengue perinatal en un centro hospitalario del departamento central de Paraguay / Perinatal dengue infection in a hospital in the central province of Paraguay

RESUMEN Introducción: La infección por dengue durante el embarazo puede poner en peligro la vida del binomio madre-hijo; es importante saber reconocerla. Objetivos: Identificar las características clínico-epidemiológicas de las embarazadas con diagnóstico (dx) de dengue en el momento del nacimiento. Describir las características clínicas y evolución de sus recién nacidos (RN). Materiales y Métodos: Serie de casos de RN de madres con dengue en el nacimiento y puerperio, durante las epidemias de dicha enfermedad en el país en los años 2012 y 2013, internados en el Servicio de Neonatología del H. Nacional. El Dx de dengue en la embarazada y el RN se consideró teniendo en cuenta la epidemiología, y/o con confirmación serológica (Viremia positiva determinada por PCR, y/o IgM positivo para dengue por Elisa de captura). Resultados: Se incluyeron 12 embarazadas y sus 13 RN, con un par de gemelares. Las madres provenían del Dpto. central y ciudades vecinas; tenían una edad de 18 años (15-34). Fueron sintomáticas 10(83,3%). 7(58,3%) de ellas requirieron internación antes del nacimiento. Los síntomas se presentaron antes del nacimiento en 6, el día del nacimiento en 1, después del nacimiento en 1, y en 2 se desconocía la duración de síntomas. Se sometieron a cesárea 8(66,6%); el motivo de la misma se debió a pre-eclampsia, eclampsia en 4(50%), sufrimiento fetal 2, gemelar en pelviana 1, y dengue en 1 caso. 2(16,6%) de las madres fallecieron. De los RN incluídos 8 fueron femeninos y 5 masculinos; se consideró a 9 RN con dx de dengue y 4 sin dengue. La EG media en cada grupo fue 36,6±1,4 y 37±2 sem. respectivamente; el peso de nacimiento de 2431±381,9 y 3076,6±899,1 gr. De 9 RN con dengue, desarrollaron síntomas 7; 1 el día del nacimiento y en 6 después de las 24 hs y <7 días. Los síntomas destacados fueron: trombocitopenia en 9; disturbios hemodinámicos, ascitis y fiebre en 7; dificultad respiratoria y derrame pleural en 4; distención abdominal en 3; rash cutáneo y edema de párpados en 2; hipoactividad, irritabilidad, hipoglucemia y vómitos en un caso cada uno. 4 RN requirieron transfusión de plaquetas. Todos fueron dados de alta vivos, con una duración de internación de 16±5,9 días.

ABSTRACT Introduction: dengue infection during pregnancy can endanger the life of the mother and child; it is important to recognize it. Objectives: To identify clinical and epidemiological pregnant woman with diagnosis (dx) of dengue at the time of child birth. To describe the clinical characteristics and outcome of newborns (RN). Material and Methods: Case series of dengue RN mothers at birth and postpartum, during epidemics of the disease in the country in 2012 and 2013, admitted to the Neonatal Service of the National H.. The Dx of dengue in pregnant and RN considered taking into account the epidemiology, and / or serological confirmation (positive viremia determined by PCR and / or positive for dengue IgM capture Elisa). Results: 12 pregnant and 13 RN were included, with a pair of twins. Mothers came from the Central Department and neighboring cities.; were aged 18 years (15-34). Symptomatic were 10 (83.3%). 7 (58.3%) of them required hospitalization before birth. The symptoms occurred before birth in 6, the day of birth to 1, after birth in 1 and 2 the duration of symptoms was unknown. They underwent cesarean section 8 (66.6%); the reason of it was due to pre-eclampsia, eclampsia in 4 (50%), fetal distress 2 twin breech 1 and dengue in 1 case. 2 (16.6%) of the mothers died. Of the RN included 8 were female and 5 male; was considered to 9 RN with dx of dengue and dengue 4 without. The average EG in each group was 36.6 ± 1.4 and 37 ± 2 sem. respectively; birth weight of 2431 ± 381.9 and 3076.6 ± 899.1 gr. From 9 new born with dengue, 7 developed symptoms; 1 the day of birth and 6 after 24 hours and <7 days. The prominent symptoms were thrombocytopenia in 9; hemodynamic disorders, ascites and fever in 7; shortness of breath and pleural effusion in 4; abdominal distension 3; skin rash and eyelid edema in 2; hypoactivity, irritability, hypoglycemia and vomiting in one case each. 4 new born required transfusion of platelets. All were discharged alive with a duration of hospitalization of 16 ± 5.9 days.

Establishment of Platelet Antigen and Antibody Tests by Mixed Passive Hemagglutination with Frozen-stored Platelets / 대한수혈학회지

BACKGROUND: Platelet antigen and antibody tests have been used in platelet immunological disorders, such as neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura (PTP). Mixed passive hemagglutination (MPHA) method has several advantages, including frozen preservation of platelets, ability to differentiate between anti-HLA and platelet-specific antibodies, and quick and easy interpretation without expensive equipment. In this study, we intended to develop the MPHA method using indicator cells of anti-Rh(D) sensitized group O, Rh+ RBCs. METHODS: We made indicator cells sensitized with anti-Rh(D) with various strengths (1:32 to 1:256) and determined the optimal strength. We determined the sensitivity of the MPHA and compared the results using flow cytometry. We observed the changes of the reaction according to the storage time of indicator cells. RESULTS: The optimal sensitization strengths of the indicator cells were 1:192 and 1:256. MPHA showed strong positive results with 1:8,192 diluted positive control, while the detection limit of flow cytometry was 1:128. Until the second week (mean 16 days), the indicator cells showed good results comparable to those of fresh ones. CONCLUSION: We developed the MPHA method using indicator cells of anti-Rh(D) sensitized group O, Rh+ RBCs. We produced the indicator cells in our own laboratory and obtained platelet panels with rare antigen typing using frozen-stored platelets. This technology will be used effectively for detection of platelet antigens and identification of platelet antibodies and also for platelet crossmatching.

Can we predict neonatal thrombocytopenia in offspring of women with idiopathic thrombocytopenic purpura?

BACKGROUND: We aimed to investigate which factors in the clinical profile of mothers with idiopathic thrombocytopenic purpura (ITP) can predict neonatal risk of thrombocytopenia. METHODS: Data was retrospectively collected from all pregnant women with ITP who presented to our institution between 2001 and 2013. Neonatal offspring of these women were classified into 2 groups based on the presence or absence of neonatal thrombocytopenia (platelet count <100x109/L). Several parameters were compared between the 2 groups, including maternal age, maternal platelet count, maternal treatment history, and thrombocytopenia in siblings. We further examined the correlation between maternal platelet count at the time of delivery and neonatal platelet count at birth; we also examined the correlation between the minimum platelet counts of other children born to multiparous women. RESULTS: Sixty-six neonates from 49 mothers were enrolled in the study. Thrombocytopenia was observed in 13 (19.7%) neonates. Maternal treatment for ITP such as splenectomy did not correlate with a risk of neonatal thrombocytopenia. Sibling thrombocytopenia was more frequently observed in neonates with thrombocytopenia than in those without (7/13 vs. 4/53, P<0.01). No association was observed between maternal and neonatal platelet counts. However, the nadir neonatal platelet counts of first- and second-born siblings were highly correlated (r=0.87). CONCLUSION: Thrombocytopenia in neonates of women with ITP cannot be predicted by maternal treatment history or platelet count. However, the presence of an older sibling with neonatal thrombocytopenia is a reliable risk factor for neonatal thrombocytopenia in subsequent pregnancies.

Trombocitopenia familiar de plaquetas gigantes: caso clínico / Familiar Thrombocytopenia of Giant Platelets: Clinical Case

La trombocitopenia es causa frecuente de consulta en hematología pediátrica. La mayoría de veces la baja de plaquetas es por desorden de destrucción autoinmune, raramente el padecimiento tiene un comportamiento familiar-hereditario. Se presenta el caso de una paciente de 11 años de edad, conocida desde los 3 años por trombocitopenia en el rango de 50,000/mm , fue evaluada por posibilidad de desórdenes autoinmunescon estudios inmunológicos básicos: complementos, ANA, Anti ADN, factor reumatoide y los resultados fueron normales. Tratada en varias ocasiones con prednisona oral, antiRh y con inmunoglobulina intravenosa (IGIV). Se le ha brindado seguimiento prolongado por trombocitopenia que resultó ser familiar; encontrando doce afectados, que incluyen abuela materna, madre, tíos, primos y hermana. Las características clínicas y la morfología plaquetaria fueron finalmente suficientes para conducir a diagnóstico inusual: el síndrome de Bernard-Soulier (SBS). El diagnóstico fue sugerido por el frotis de sangre periférica (FSP)...

A case of neonatal alloimmune thrombocytopenia purpura caused by anti HPA-3a antibody and literature review / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the diagnosis and treatment of a case of neonatal alloimmune thrombocytopenia purpura (NAITP) caused by anti HPA-3a antibody.</p><p><b>METHODS</b>The platelet counts and purpuric symptom in the newborn were clinical examined. The HPA-1-21bw genotypes of the newborn and his parents were detected by multiple DNA-PCR, gene sequencing and genotyping. The HPA specificity antibody in the sera of newborn and his mother were detected by flow cytometry (FCM), and the HPA specificity antibody was identified by monoclonal antibody-specific immobilization of platelet antigens (MAIPA).</p><p><b>RESULTS</b>The newborn had the typical symptom of NAITP, multiple subcutaneous petechia, hematuria and coffee-like vomitus. The HPA genotype of the newborn was HPA-3ab, while that of his mother and his father were HPA-3bb and HPA-3aa, respectively. The sera of newborn and his mother existed antibody against the platelet of newborn's father. The HPA antibody of the newborn and his mother were identified as anti HPA-3a. The newborn was approved a patient of NAITP caused by anti HPA-3a antibody.</p><p><b>CONCLUSION</b>The diagnosis and treatment for NAITP newborn caused by anti HPA-3a antibody in this study was the first domestic report. It could provide successful experiences and references for the similar cases.</p>

Human Platelet Antigen Genotyping Using a Multiplex Single-Base Primer Extension Reaction in Koreans / 대한수혈학회지

BACKGROUND: Alloimmunization of human platelet antigens (HPA) is associated with clinically significant disease, such as platelet refractoriness, neonatal alloimmune thrombocytopenia, or posttransfusion purpura. It is determined by single nucleotide polymorphism of genes for platelet membrane glycoprotein. To date, approximately 27 HPAs have been discovered, and their frequencies differ depending on ethnicity and country. METHODS: We conducted an investigation of prevalence of HPA in the Korean population using a multiplex single-base primer extension reaction (SNaPshot). With 84 specimens from healthy donors, HPA genotyping was performed on 11 different HPAs, including HPA-1, -2, -3, -4, -5, -6, -7, -8, -9, -13, and -15. RESULTS: A total of 90 blood samples were genotyped. The genotype frequencies of HPA were as follows: HPA-1a/1a: 100.0%, -2a/2a: 83.3%, -2a/2b: 14.3%, -2b/2b: 2.4%, -3a/3a: 39.3%, -3a/3b: 52.4%, -3b/3b: 8.3%, -4a/4a: 100.0%, -5a/5a: 95.2%, -5a/5b: 4.8%, -6a/6a: 94.0%, -6a/6b: 6.0%, -7a/7a: 100.0%, -8a/8a: 100.0%, -9a/9a: 97.6%, -9a/9b: 2.4%, -13a/13a: 100.0%, -15a/15a: 23.8%, -15a/15b: 51.2%, and -15b/15b: 25.0%. CONCLUSION: The SNaPshot assay was employed for detection of SNPs in various clinically significant HPA genes. In addition to well-known frequencies of previously reported HPA-1 to -8, this study showed frequencies of HPA-9, -13, and -15 in Koreans for the first time. The SNaPshot technique might be suitable for use in actual clinical testing in patients with platelet alloimmunization.

Neonatal Alloimmune Thrombocytopenia Caused by Anti-HLA-A2 Alloantibodies Determined by Luminex Single Antigen Bead Assay

Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies react to antigens expressed on fetal platelets, which is mainly platelet-specific alloantigen or HLA, resulting in their immune destruction. Here, we described a patient who suffered from NAIT caused by anti-HLA-A2 antibody. Sera from the mother and the newborn were screened for human platelet antigen-specific antibodies and HLA antibodies by ELISA, and HLA antibodies were detected in both of them. The antibody specificity was identified as anti-HLA-A2 by Luminex single antigen bead assay. HLA typing results showed that patient's father descended HLA-A2 antigen on the patient and the mother was HLA-A2 negative. It is most conceivable that anti-HLA-A2 alloantibody in the mother's sera crossed the placenta and subsequently caused NAIT in the case presented. The patient received platelet concentrates, oral steroid and intravenous globulin and platelet count increased to 120x10(9)/L on the 90th day of life. The Luminex single antigen bead assay used in this case is highly sensitive and specific assay to determine antibody specificity and it is faster and more convenient for routine use in clinical laboratory so that this assay could be useful to diagnose NAIT caused by HLA antibodies and treat such NAIT patients with HLA matched platelet transfusion.

Advance in thrombopoietic drugs used in treatment of children's immune thrombocytopenia / 中国实验血液学杂志

Immune thrombocytopenia (ITP) is a common acquired hemorrhagic disease. Conventional view considered its pathogenesis as the destruction of platelets induced by platelet associated antibodies, the target of treatment are inhibiting the production of antibodies and blocking the destruction of platelets in reticuloendothelial system, but they are ineffective in part of ITP patients, who transform to chronic/refractory ITP (C/RITP). As to children's C/RITP, the effect of first-line therapy is low, while the second-line therapy isn't effective definitely and has obvious side effects. The safe and effective second-line drugs to prevent disease progressing are urgently required. Recently, a pathogenesis that decrease the platelet production has been confirmed, thrombopoietic drugs, including thrombopoietin (TPO) and its receptor agonist (TRA), are under research and clinical application gradually. Recombinate human TPO (rhTPO) has accomplished Phase III clinical trails in adult C/RITP and tumor children. The Phase III clinical trails of romiplostim and eltrombopag, as the representative of TRA, in adult C/RITP have been performed. There are also two clinical trails of TRA for children's C/RITP, the efficacy and safety have been approved, with the convenience for using. In pediatric population, they have a good clinical application. In this article the research and development of thrombopoietic drugs and their perspective in pediatric clinical use are reviewed.

Prevalencia de plaquetopenia en niños infectados con el virus de la inmunodeficiencia humana en un Centro de Referencia / Prevalence of thrombocytopenia in children infected with human immunodeficiency virus in a Reference Center

Las alteraciones hematológicas son frecuentes en los niños infectados por el VIH; la plaquetopenia es una de ellas. El objetivo del estudio fue analizar la cantidad de niños infectados con el VIH que presentaron plaquetopenia y secundariamente alertar sobre la necesidad de plantear el VIH frente a un niño que se presenta con esa alteración. Material y métodos: estudio retrospectivo analizando historias clínicas de niños infectados con el VIH y que tuvieran menos de 100.000 plaquetas/mm3 en dos hemogramas separados por al menos 30 días. Se clasificaron de acuerdo a la evolución de la plaquetopenia: de reciente inicio, persistente y crónico. Resultados: 15 (8%) de 183 niños infectados con el VIH presentaron plaquetopenia en algún momento de su evolución. Todos fueron infectados por transmisión materno-infantil. 10 (67%) presentaron plaquetopenia de curso crónico y cinco (33%) de curso agudo. En dos niños la plaquetopenia fue el signo que permitió el diagnóstico del VIH; en otros dos el diagnóstico de la infección se hizo años después de la plaquetopenia. En ningún caso se hizo mielograma; los tratamientos fueron variados. Ningún paciente presentó plaquetopenia refractaria. Conclusiones: el 8% de los pacientes infectados con el VIH presentó plaquetopenia. En dos de los 15 el debut fue como PTA y no se realizó el diagnóstico de VIH y en otros dos fue la manifestación inicial de la enfermedad. Los autores plantean la necesidad de pensar en el VIH frente a un niño que presenta un PTA.