Púrpura trombótica trombocitopénica en pediatría. Reporte de un caso / Thrombotic thrombocytopenic purpura in pediatrics. A case report

La púrpura trombótica trombocitopénica es una entidad poco frecuente en pediatría, pero de alta mortalidad sin tratamiento adecuado y oportuno. Se caracteriza por presentar anemia hemolítica microangiopática asociada a signos y síntomas neurológicos, cardíacos, abdominales y menos frecuentemente renales; puede estar acompañada de fiebre. En niños, el diagnóstico se basa en los hallazgos clínicos y de laboratorio. La actividad de ADAMTS13 <10 % apoya, pero no confirma el diagnóstico y, dada la gravedad de la patología, el resultado no debe retrasar el inicio del tratamiento. Se presenta una paciente de 15 años, previamente sana, con signos neurológicos asociados a anemia hemolítica y trombocitopenia. Durante su internación, se arribó al diagnóstico de púrpura trombótica trombocitopénica adquirida.

Thrombotic thrombocytopenic purpura is a rare disease in pediatrics, but it has a high mortality if not managed in an adequate and timely manner. It is characterized by microangiopathic hemolytic anemia associated with neurological, cardiac, abdominal, and less frequently, renal signs and symptoms; it may be accompanied by fever. In children, diagnosis is based on clinical and laboratory findings. ADAMTS13 activity < 10% supports the diagnosis but does not confirm it and, given its severity, the result should not delay treatment initiation. Here we describe the case of a previously healthy 15-year-old female patient with neurological signs associated with hemolytic anemia and thrombocytopenia. During hospitalization, she was diagnosed with acquired thrombotic thrombocytopenic purpura.

Relapse of congenital thrombotic thrombocytopenic purpura, after spontaneous remission, in a second-trimester primigravida: case report and review of the literature / Recidiva, após remissão espontânea, de púrpura trombocitopênica trombótica congênita em primigesta no segundo trimestre de gestação: relato de caso e revisão da literatura

ABSTRACT CONTEXT: Thrombotic microangiopathy syndrome or thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) describes distinct diseases sharing common pathological features: microangiopathic hemolytic anemia and thrombocytopenia, without any other apparent cause. CASE REPORT: An 18-year-old second-trimester primigravida presented with a history of fifteen days of intense weakness, followed by diarrhea over the past six days. She reported having had low platelets since childhood, but said that she had never had bleeding or menstrual abnormalities. Laboratory investigation showed anemia with schistocytes, thrombocytopenia and hypohaptoglobulinemia. Red blood cell concentrate and platelet transfusions were performed. The hypothesis of TTP or HUS was put forward and ADAMTS13 enzyme activity was investigated. The patient evolved with increasing platelet counts, even without specific treatment, and she was discharged. One month afterwards, she returned presenting weakness and swollen face and legs, which had developed one day earlier. The ADAMTS13 activity was less than 5%, without presence of autoantibodies. Regarding the two previous admissions (at 9 and 16 years of age), with similar clinical features, there was spontaneous remission on the first occasion and, on the second, the diagnosis of TTP was suspected and plasmapheresis was performed, but ADAMTS13 activity was not investigated. CONCLUSION: To date, this is the only report of congenital TTP with two spontaneous remissions in the literature This report reveals the importance of suspicion of this condition in the presence of microangiopathic hemolytic anemia and thrombocytopenia without any other apparent cause.

RESUMO CONTEXTO: A síndrome de microangiopatia trombótica, ou púrpura trombocitopênica trombótica-síndrome hemolítico urêmica (PTT-SHU), descreve doenças diversas com clínica e achados patológicos comuns: anemia hemolítica microangiopática e trombocitopenia, na ausência de outra causa aparente. RELATO DO CASO: Primigesta de 18 anos no segundo trimestre apresenta-se com quadro de 15 dias de fraqueza intensa seguida por diarreia há seis dias. Relata ter plaquetas baixas desde a infância e nega sangramentos e anormalidades menstruais. Investigação laboratorial identificou anemia com esquizócitos, plaquetopenia e hipo-haptoglobulinemia. Foi realizada transfusão de plaquetas e concentrado de hemácias. A hipótese de PTT ou SHU foi aventada e realizou-se pesquisa da atividade da enzima ADAMTS13. A paciente evoluiu com elevação das plaquetas, mesmo sem tratamento específico, tendo alta. Retornou após um mês da alta com queixa de fraqueza há um dia e inchaço de face e pernas. A atividade da ADAMTS13 foi menor que 5%, sem autoanticorpos. Nas duas internações anteriores (aos 9 e 16 anos), com quadros similares, houve remissão espontânea na primeira internação e, na segunda, o diagnóstico de PTT foi suspeitado e foi realizada plasmaférese, porém sem a pesquisa da atividade da ADAMTS13. CONCLUSÃO: Até esta data, este é único relato de TTP congênita com duas remissões espontâneas na literatura. Este relato revela a importância da suspeição desta patologia na presença de anemia hemolítica microangiopática e trombocitopenia sem outra causa aparente.

Púrpura trombótica trombocitopénica y tuberculosis: Una rara asociación / Thrombotic thrombocytopenic purpura and tuberculosis. A rare association

La púrpura trombótica trombocitopénica (PTT) es una microangiopatía trombótica asociada a cuadros de trasplante de células madre hematopoyéticas, embarazo y posparto, al uso de ciertas drogas, diarrea sanguinolenta, a un grupo heterogéneo de trastornos como enfermedades autoinmunes, hipertensión maligna, enfermedades neoplásicas, diversas infecciones y un grupo llamado idiopático, donde se incluyen aquellos en quienes no se cumplieron los criterios de las categorías clínicas anteriores. La tuberculosis (TBC) es una enfermedad de incidencia intermedia en Argentina, más frecuente en determinados grupos poblacionales. Presentamos el caso de un varón de 60 años que consulta por dolor abdominal, tos y sudoración nocturna; se detectó primero trombocitopenia y luego de algunos días anemia microangiopática, lo que llevó al diagnóstico de PTT. Posteriormente, al continuar con la evaluación, se diagnosticó TBC por: 1) baciloscopia positiva para bacilos ácido-alcohol resistentes (+++) por técnica de Ziehl Neelsen en lavado broncoalveolar, 2) lesiones en laringe y 3) lesiones en válvula ileocecal. La TBC ha sido pocas veces asociada con la PTT en la literatura, razón por la cual presentamos este caso.

Thrombocytopenic thrombotic purpura (TTP) is a thrombotic microangiopathy associated with hematopoietic stem cells transplantation, pregnancy, puerperium, drugs, bloody diarrhea, a heterogeneous group of illnesses, such as malignant hypertension, autoimmune and neoplastic diseases, infections, and an idiopathic group that includes the pathologies that don’t apply for the preceding clinical categories. Tuberculosis is an illness of intermediate incidence in Argentina, with increased frequency in high-risk groups. In this article, we present the case of a 60 years old male patient, with abdominal pain, cough and nocturnal sweating. He was diagnosed as having thrombocytopenia, and a few days later, microangiopathic anemia and TTP. Further examinations led TBC diagnosis based on: 1) acid fast bacillus (+++) for Ziehl Neelsen stain in bronco alveolar lavage, 2) laryngeal lesion and 3) ileocecal valve lesion. We report this case, because TBC has rarely been associated with TTP in medical literature.

Cerebellar degeneration and immune thrombocytopenic purpura associated with human immunodefi ciency virus infection (HIV)

Cerebellar disorders associated with HIV infection are usually caused by opportunistic infections, central nervous system lymphoma, and toxic effects of medicines, nutritional and metabolic disorders, and cerebrovascular disease. We present an unusual association of cerebellar degeneration and immune thrombocytopenic purpura in a 28-years-old woman HIV infected. An autoimmune aetiology is likely.

Transtornos cerebelares associados a infecção pelo HIV são comumente causados por infecções oportunistas, linfoma do sistema nervoso central, efeitos tóxicos de medicamentos anti-retrovirais, alterações metabólicas e nutricionais, e doença cerebrovascular. Apresentamos um caso incomum de associação de degeneração cerebelar e púrpura trombocitopênica imunológica em um mulher de 28 anos infectada pelo HIV. Discutimos uma possível etiologia autoimune para justificar o quadro.

Central retinal vein occlusion associated with thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome: complete resolution is possible.

We aim to describe a case of central retinal vein occlusion associated with this is a case report of a 45-year-old patient who was admitted for management of thrombotic thrombocytopenic purpura (TTP). He developed left central retinal vein occlusion three months later. The retinal vein occlusion resolved gradually as his TTP started to respond to medical treatment but significant macular edema persisted. Focal argon laser treatment resulted in complete resolution of the macular edema.

Aspectos neurológicos del púrpura trombótico trombocitopénico: Presentación de un caso / Thrombotic thrombocytopenic purpura with neurological involvement: Report of one case

Neurological manifestations, secondary to perfusion problems, vasogenic edema or small infarcts, are common in thrombotic purpura. Moreover, they are the first symptoms of the disease in 50% of patients. We report a 50 year-old woman who presented with focal intermittent neurological signs with aphasia and right hemiparesis, who then developed progressive impairment of consciousness with stupor and generalized tonic-clonic seizures. Despite the severe neurological impairment, first neuroimaging studies were normal. A second magnetic resonance imaging showed small cortical infarcts, that were visible only with the technique of diffusion weighted imaging. The standard electroencephalograms showed focal left temporal slowing and low voltage first and then diffuse slowing accordind to the clinical condition of the patients. She was treated with plasmapheresis and had a partial neurological recovery at the fifth day, but died at the twelfth day of therapy .

Sindrome uremico hemolitico: ubicación nosologica actual / Hemolytic uremic syndrome (HUS): an up-dated nosological classification

An up-date of the causes and pathogenesis of the HUS is reported. After more than 40 years of research we are able to define the infectious agents and the toxin involved. The mechanisms and the molecules involved in the non-diarrheal (atypical) entities producing HUS have also been characterized. This new situation allows us to develop a diagnostic algorithm that enables us to better define preventive and therapeutic measures, based on more rational evidence.

Thrombotic thrombocytopenic purpura-induced posterior leukoencephalopathy in a patient without significant renal or hypertensive complications.

A 40-year-old male with recent-onset idiopathic thrombotic thrombocytopenic purpura (TTP) developed focal transient neurological findings lasting for several hours, remitting, then recurring in a different pattern. Brain magnetic resonance imaging (MRI) was consistent with a posterior leukoencephalopathy and electroencephalography demonstrated lateralized slowing during an episode. No acute ischemic changes were found on diffusion-weighted imaging. Close monitoring in an intensive care setting revealed no significant hypertensive episodes. The patient's condition resolved with plasmapheresis and immunoglobulin therapy. The relation of TTP to reversible posterior leukoencephalopathy syndromes is discussed. Clinical features of this case suggest a mechanism for TTP-induced leukoencephalopathy independent of hypertension and renal failure.

Microangiopatías trombóticas: SUH/PTT: aspectos fisiopatológicos / Trombotic microangiopathies: SUH/PTT: physiopathological aspects

La causa y mecanismo de la lesión de la célula endotelial (CE) y el mecanismo que provoca la trombosis son los hechos fisiopatológicos más importantes y aún no totalmente conocidos como el Sindrome Urémico Hemolítico/Púrpura Trombocitopénica Trombótica (SUH/PTT). En el SUH asociado a Toxina de Shiga, la lesión de la CE es provocada por la toxina, que penetra a la célula a través de un receptor glicolipídico (Gb3) y altera la síntesis de proteínas celulares a nivel de los ribosomas, provocando la muerte celular por injuria o apoptosis. Existirían mecanismos que amplifican o facilitan la lesión endotelial por la toxina, a través de secreciones de citoquinas inflamatorias, activación de neutrófilos, etc. También se postula que existen factores condicionantes para la aparición de este síndrome, que podrían ser inmunológicos o genéticos. En las otras formas clínicas de SUH/PTT, idiopáticas, secundarias o familiares, tanto esporádicas como recurrentes, el mecanismo de la lesión de la CE no es conocido, pero pueden ser múltiples de acuerdo con cuál sea el cuadro clínico con el que se asocia (idiopático, infecciones, drogas, embarazo, enfermedades autoinmunes, etc.) También podrían existir mecanismos amplificadores de la lesión endotelial (citoquinas) y factores genéticos de predisposición, como el déficit de factor H del complemento en SUH familiar o esporádicos. En cuanto al mecanismo de la trombosis, la lesión o activación de la CE, al disminuir su tromborresistencia y aumentar su capacidad trombogénica, puede inducir la trombosis por múltiples mecanismos (activación de coagulación, activación plaquetaria e hipofibrinolisis). Se enfatizan las alteraciones de su membrana con disminución de los sistemas inhibidores de coagulación, expresión de Factor Tisular, disminución de los sistemas inhibidores de coagulación, expresión de Factor Tisular, disminución del sistema de ectoadepeasa (CD39), la liberación de FvW, etc., como mecanismos trombogénicos relevantes. Las modificaciones del FvW ("multímeros ultragrandes" o "multímeros pequeños") por una alteración en el clivaje de su molécula que genera multímeros con mayor afinidad y actividad agregante plaquetaria, es un mecanismo importante para mantener y aumentar el proceso trombótico, pero no parece ser el único mecanismo trombogénico en esta patología. La descripción reciente de "déficit congénito de la proteasa de FvW" en casos de PTT familiares y de déficit funcional de esta "proteasa"...

Purpura trombocitopenica trombotica y lupus eritematoso sistemico. Tres casos con presentacion simultanea / Thrombotic thrombocytopenic purpura and systemic lupus erythematosus. Three cases with simultaneous presentation

La púrpura trombocitopénica trombótica (PTT) es un síndrome clínico caracterizado por anemia hemolítica microangiopática, trombocitopenia, fiebre, déficits neurológicos fluctuantes y enfermedad renal. Su asociación con lupus eritematoso sistémico (LES) se reconoció en la literatura médica desde 1939. Las dos enfermedades presentan manifestaciones clínicas simmilares por lo que en ocasiones es dificultoso establecer la presencia de PTT en un paciente con LES activo. La identificación de esquistocitos en el frotis de sangre periférica es crucial para el diagnóstico, así como la reticulocitosis marcada y la negatividad en la reacción de Coombs directa. Presentamos tres pacientes de sexo feminino en las que las dos entidades se presentaron en forma simultánea. Sugerimos la utilización de inmunosupresores junto con tratamiento de plasmaféresis con reposición de sobrenadante de crioprecipitado.

A case of Wegener's granulomatosis complicated by diffuse pulmonary hemorrhage and thrombotic thrombocytopenic purpura

Wegener's granulomatosis is a distinct form of necrotizing granulomatous vasculitis which usually affects the kidneys and the upper and lower respiratory tracts. Unusual manifestations have also been reported, and these include colitis, urethritis and diabetes insipidus. We describe a case of Wegener's granulomatosis which presented with rapidly progressive renal insufficiency, sudden deafness, red eye, facial palsy, and complicated by uncommon manifestations that were diffuse pulmonary hemorrhage and thrombotic thrombocytopenic purpura.

A misteriosa púrpura trombocitopênica trombótica (doença de Moschcowitz): discussao de um caso / The enigmatic purpura thrombotic thrombocytopenic (moschkowitz syndrome): discussion of a case

É relatado o caso de um paciente adulto jovem com quadro agudo de púrpura trombocitopênica trombótica (PTT), cujo diagnóstico diferencial incluiu as possibilidades de dengue hemorrágico, leptospirose e febre tifóide, por serem patologias endêmicas da regiäo. Posteriormente, configuraram-se características e laboratoriais da PTT, que necessitou ainda diferenciaçäo com a síndrome hemolítico-urêmica e com a da coagulaçäo intravascular disseminada (CID). O tratamento, com plasma fresco, plasmaferese e fraçäo sobrenadante de crioprecipitado, levou à cessaçäo do processo, continuando o enfermo em observaçäo

Púrpura trombótica trombocitopénica y seropositividad para el virus de la inmunodeficiencia humana adquirida / Thrombotic thrombocytopenic purpura and human acquired immunodeficiency virus seropositivity

La púrpura trombótica trombocitopénica (PTT) es una enfermedad de etiología desconocida,c aracterizad aclínicamene por una péntada diagnóstica (trombocitopenia, anemia hemolítica mciroangiopática, signos y síntomas neurológicos, fiebre y lesión renal). Trabajos recientes describen por primera vez su asociación con el virus dela inmunodeficiencia humana adquirida (HIV). Se comenta el caso clínico de una paciente con diagnóstico de PTT en quien se halló seropositividad para HIV. El daignóstico de PTT fue confirmado con los hallazgos histopatológicos de biopsias y autopsia, en la que se observó la característica microtrombosis sistémica de capilares y arteriolas

Púrpura trombocitopênica trombótica com insuficiência renal aguda, induzida por toxinas de larvas de borboleta: relato de um caso / Thrombotic thrombocytopenic purpura with acute renal failure, induced by toxins of the butterfly larva: report of a case

O paciente aqui relatado apresentou um quadro de trombocitopenia, disfunçäo renal, febre, após ser ferida por larvas de borboleta; näo apresentando anormalidades neurológicas, o que caracterizaria a síndrome de Moschcowitz. O quadro de anemia hemolítica com células vermelhas fragmentadas foi positivo, o que nos levou a pensar no diagnóstico de Púrpura Trombocitopênica Trombótica (TTP), mas estudo histológico näo foi realizado. Neste presente caso, relata-se a remissäo sustentada do quadro clínico após transfusöes de sangue fresco e sessöes de hemodiálises, precocemente instituidas