Síndrome antifosfolipídico en pediatría: a propósito de un caso / The antiphospholipid antibody syndrome in pediatrics: a case repor

El síndrome antifosfolipídico (SAF) es infrecuente en la edad pediátrica (3 %) y se presenta como eventos trombóticos de lechos vasculares y/o abortos espontáneos, asociado a la presencia de anticuerpos antifosfolipídicos (aFL). Este síndrome puede ser primario o asociado a alguna enfermedad sistémica subyacente. Se presenta el caso de una niña de 12 años con hemiparesia faciobraquiocrural derecha y alteración en la marcha de aparición aguda, en la cual se confirma un accidente cerebrovascular (ACV) isquémico por trombosis de la arteria cerebral media asociado a aFL positivos (anticuerpo anticardiolipina, anticoagulante lúpico y anticuerpo anti-ß2-glicoproteína). Cumple con los criterios para realizar diagnóstico de síndrome antifosfolipídico. Luego de iniciar el tratamiento, la paciente evoluciona de manera favorable. Se trata de una patología infrecuente y de presentación variable, por lo que requiere un alto sentido de alerta por parte del equipo de salud para evitar retrasos en el diagnóstico y el tratamiento, y disminuir su morbimortalidad

Antiphospholipid syndrome (APS) is infrequent at pediatric age (3 %) and is characterized by venous or arterial thrombosis and/or spontaneous abortions. APS occurs either as a primary condition or in the setting of an underlying disease. This is a case of a 12-year-old girl with a right hemiparesis and acute disturbance in gait, in which an ischemic cerebrovascular accident (CVA) due to middle cerebral artery thrombosis associated with positive antiphospholipid antibodies is confirmed (anticardiolipin antibody, lupus anticoagulant and anti-ß2-glycoprotein antibody), fulfilling the criteria for the diagnosis of antiphospholipid syndrome . After starting treatment accordingly, the patient evolves favorably. As this pathology is infrequent and of variable presentation, it requires a high sense of alert from the health team to avoid delays in diagnosis and treatment

[The antiphospholipid antibody syndrome in pediatrics: a case report]. / Síndrome antifosfolipídico en pediatría: a propósito de un caso.

Antiphospholipid syndrome (APS) is infrequent at pediatric age (3 %) and is characterized by venous or arterial thrombosis and/or spontaneous abortions. APS occurs either as a primary condition or in the setting of an underlying disease. This is a case of a 12-year-old girl with a right hemiparesis and acute disturbance in gait, in which an ischemic cerebrovascular accident (CVA) due to middle cerebral artery thrombosis associated with positive antiphospholipid antibodies is confirmed (anticardiolipin antibody, lupus anticoagulant and anti-ß2-glycoprotein antibody), fulfilling the criteria for the diagnosis of antiphospholipid syndrome. After starting treatment accordingly, the patient evolves favorably. As this pathology is infrequent and of variable presentation, it requires a high sense of alert from the health team to avoid delays in diagnosis and treatment.

El síndrome antifosfolipídico (SAF) es infrecuente en la edad pediátrica (3 %) y se presenta como eventos trombóticos de lechos vasculares y/o abortos espontáneos, asociado a la presencia de anticuerpos antifosfolipídicos (aFL). Este síndrome puede ser primario o asociado a alguna enfermedad sistémica subyacente. Se presenta el caso de una niña de 12 años con hemiparesia faciobraquiocrural derecha y alteración en la marcha de aparición aguda, en la cual se confirma un accidente cerebrovascular (ACV) isquémico por trombosis de la arteria cerebral media asociado a aFL positivos (anticuerpo anticardiolipina, anticoagulante lúpico y anticuerpo anti-ß2- glicoproteína). Cumple con los criterios para realizar diagnóstico de síndrome antifosfolipídico. Luego de iniciar el tratamiento, la paciente evoluciona de manera favorable. Se trata de una patología infrecuente y de presentación variable, por lo que requiere un alto sentido de alerta por parte del equipo de salud para evitar retrasos en el diagnóstico y el tratamiento, y disminuir su morbimortalidad.

Sickle cell trait: a cause of abdominal pain and pulmonary embolism.

INTRODUCTION: Sickle cell trait (SCT) is a rare and underdiagnosed disorder in the Argentinian population. In this condition, individuals carry the mutation of the HbS gene in one of the two beta-globin genes. In general, SCT does not present with the typical manifestations of sickle cell anemia. However, under certain circumstances, some clinical characteristics of the disease may develop. METHODS: We discussed the case of a 39-Year old man who presented with persistent abdominal pain of unknown origin after traveling to a high-altitude place. He underwent laparotomy without a definite diagnosis. After that, the patient developed signs of splenic infarction and pulmonary thromboembolism that were confirmed by computed tomography. RESULTS: A sickling test was positive, and a hemoglobin electrophoresis revealed an abnormal fraction at the HbS level. In this context a diagnosis of SCT was made. Additional, tests revealed a strongly positive lupus anticoagulant. CONCLUSION: SCT presentation as abdominal pain and thromboembolic disease in adult patients after exposure to high altitudes is a rarely suspected diagnosis.

Life-threatening hemorrhage secondary to acquired deficiency of coagulation factors VIII and XI related to systemic lupus erythematosus: case report / Hemorragia severa secundaria a deficiencia adquirida de factores VIII y XI de la coagulación relacionada con lupus eritematoso sistémico: reporte de caso

ABSTRACT In patients with autoimmune diseases, the simultaneous occurrence of lupus anticoagulant and blood coagulation factors inhibitors is infrequent and is associated with hemorrhagic events. In these cases, the initial approach requires a thorough interpretation of coagulation laboratory tests and mixing studies to reach a definitive diagnosis. We report the case of a patient with systemic lupus erythematosus and Sjögren's syndrome who presented with hemorrhagic diathesis caused by circulating inhibitors against factors VIII and XI coexisting with lupus anticoagulant. The inhibitors eradication was made with rituximab, achieving good results.

RESUMEN La ocurrencia simultánea de anticoagulante lúpico e inhibidores circulantes contra los factores de la coagulación es infrecuente en los pacientes con enfermedad autoinmune, y está relacionada con eventos hemorrágicos. El abordaje inicial requiere una adecuada interpretación de los tiempos de coagulación y prueba de mezcla con plasma para alcanzar el diagnóstico definitivo. Se reporta el caso de una paciente con lupus eritematoso sistémico y síndrome de Sjögren, quien se presentó con trastorno hemorrágico amenazante de la vida ocasionado por inhibidores circulantes contra los factores VIII y XI de la coagulación en coexistencia con anticoagulante lúpico. El tratamiento de erradicación de los inhibidores se realizó con rituximab, con buenos resultados.

Models for releasing the lupus anticoagulant test / Modelos de liberação do teste anticoagulante lúpico

ABSTRACT Introduction: Thrombophilia is a thrombosis susceptibility of genetic, acquired or mixed nature. Among acquired causes, the antiphospholipid syndrome (APS) stands out as an autoimmune disease characterized by antiphospholipid antibodies, thrombotic events or recurrent gestational loss. Laboratory diagnosis is based on the detection of lupus anticoagulant (LAC), anti-β2-glycoprotein 1 and anticardiolipin; however the determination of LAC still demands uniformity. The last guideline published by the Clinical and Laboratory Standards Institute (CLSI) prioritizes the screening and confirmatory steps, to the detriment of the mixing phase. Objectives: To compare the forms of releasing the LAC and to adopt an investigation protocol in agreement with the international guidelines. Methods: Thirty-six samples with prolonged results in the screening step by the dilute Russell viper venom time (dRVVT) or activated partial thromboplastin time (APTT) were subjected to the mixing steps (1:1) and to the confirmatory steps with high concentrations of phospholipids. Results: For APTT, values whose indexes of circulating anticoagulant (ICA) were greater than 15% were considered positive. For dRVVT, the ratio between screening and confirmation was also used. Of the 36 tested samples, 14 showed correction in the mixing step, but only one resulted negative. Conclusion: ICA aided in identifying the weak antibodies that were probably diluted in the mixing step. There is no gold standard test for the diagnosis of APS, and LAC detection still requires standardization of technique and interpretation.

RESUMO Introdução: Trombofilia é a suscetibilidade à trombose, de natureza genética, adquirida ou mista. Entre as causas adquiridas, destaca-se a síndrome do anticorpo antifosfolípide (SAF) - doença autoimune caracterizada por anticorpos antifosfolípides, eventos trombóticos ou perda gestacional recorrente. O diagnóstico laboratorial baseia-se na detecção do anticoagulante lúpico (ACL), do anti-β2-glicoproteína 1 e da anticardiolipina; entretanto a execução do ACL ainda demanda uniformização. A última diretriz publicada pelo Clinical and Laboratory Standards Institute (CLSI) prioriza as etapas de triagem e confirmatória, em detrimento da mistura. Objetivos: Comparar as formas de liberação do ACL e adotar um protocolo de investigação em anuência às normas internacionais. Métodos: Trinta e seis amostras com resultados prolongados na etapa de triagem pelo ensaio do tempo do veneno da víbora de Russel (dRVVT) ou tempo de tromboplastina parcial ativada (TTPA) foram submetidas às etapas de mistura (1:1) e confirmatórias com altas concentrações de fosfolipídios. Resultados: Para o TTPA, foram considerados positivos os valores cujo cálculo do índice de circulação de anticoagulante (ICA) resultasse superior a 15%. Para o dRVVT, utilizou-se também o valor da razão entre triagem e confirmatória. Das amostras testadas, 14 revelaram correção na etapa da mistura, mas somente uma resultou em pesquisa negativa. Conclusão: O cálculo do ICA auxiliou na identificação dos anticorpos fracos que possivelmente sofreram diluição na etapa da mistura. Não há um exame padrão-ouro para o diagnóstico da SAF, e a pesquisa do ACL ainda demanda uniformização da técnica e da interpretação.

Síndrome Antifosfolipídico Catastrófico / Catastrophic Antiphospholipid Syndrome

El término síndrome antifosfolipídico (SAF) "catastrófi-co" fue introducido para definir una forma grave y rá-pidamente evolutiva de SAF que conduce a insuficien-cia multiorgánica. Los pacientes con SAF catastrófico tienen en común: a) evidencia clínica de afectación orgánica múltiple (3 o más órganos); b) evidencia ana-tomopatológica de la oclusión de múltiples vasos de pequeño calibre (aunque algunos pacientes presentan también trombosis de los vasos de gran calibre) y c) confirmación de la presencia de anticuerpos antifosfoli-pídicos (AAF), generalmente a títulos elevados. Aunque representan menos del 1% de todos los pa-cientes con SAF, generalmente se encuentran en una situación médica urgente que requiere un seguimiento clínico exhaustivo y un tratamiento precoz y enérgico.

The term anti-phospholipid syndrome (APS) "catastro-phic" was introduced to define a serious and rapidly progressive form of APS which leads to multi-organ failu-re. Patients with catastrophic APS have in common: a) a clinical evidence of multiple organ involvement (3 or more organs); b) pathological evidence of occlusion of multiple small vessels (although some patients have also thrombosis of large vessels) and c) confirmation of the presence of anti-phospholipid antibodies (APAs), usually at high titers.Although they represent less than 1% of all patients with APS, they usually found in an urgent medical situation that requires a thorough clinical monitoring and an early and vigorous treatment.

Neurofibromatosis type I and anti-phospholipid antibody syndrome: Report of one case / Neurofibromatosis tipo I y síndrome antifosfolípidos: Informe de un caso

Neurofibromatosis type I (NF1) has been only rarely reported in association with anti-phospholipid syndrome (APS). We report a 38 year-old female with NF1, who developed a cervix carcinoma at the age of 30 years and was successfully treated with conization, without requiring chemotherapy or radiation. She experienced two miscarriages prior to the diagnosis of the carcinoma. When she was 38 years old, an APS was diagnosed based on repeatedly positive lupus anticoagulant tests. The patient continued to smoke and using oral contraceptives. At 38 years of age she had a myocardial infarction, despite the use of oral anticoagulation. She required coronary stenting. Aspirin and clopidrogel were indicated thereafter.

Es inusual la asociación entre neurofibromatosis tipo I (NF1) y síndrome antifosfolípidos (APS). Presentamos una paciente mujer de 38 años con un NF1 que desarrolló un cáncer cervicouterino a los 30 años y que fue tratada exitosamente con una conización, sin requerir quimioterapia o radiación. La paciente tuvo dos abortos espontáneos antes del diagnóstico del carcinoma. A los 38 años, se le diagnosticó un APS, basado en pruebas de anticoagulante lúpico que resultaron positivas en repetidas oportunidades. La paciente continuó fumando y usando contraceptivos orales y, a pesar de estar con anticoagulantes orales, tuvo un infarto agudo de miocardio a los 38 años. Se colocó un stent coronario y se indicó aspirina y clopidogrel.

Síndrome antifosfolípido: generalidades y diagnóstico / Antiphospholipid syndrome: clinical and laboratory diagnosis

Resumen: El síndrome antifosfolípido ha sido un tema de investigación continua en diferentes áreas de la medicina. El diagnóstico clínico y de laboratorio se realiza teniendo en cuenta los consensos inter-nacionales de Sapporo (1999) y Sydney (2006), los cuales dan las pautas para identificar y caracterizar el síndrome antifosfolípido. El objetivo primordial de este artículo, es describir los avances científicos en el estudio del síndrome antifosfolípido, los criterios actuales de clasificación, el papel de los anti-cuerpos anticardiolipina, anti β2 glicoproteína I y el anticoagulante lúpico, así como los mecanismos patogénicos e inmunológicos en los que están involucrados estos anticuerpos. También se describen algunas de las manifestaciones clínicas relacionadas y los procedimientos diagnósticos utilizados ac-tualmente para su identificación.

Abstract: Antiphospholipid syndrome has been a topic of ongoing research in different areas of medicine.Clinical and laboratory diagnosis are performed taking into account international guidelines to identify and characterize antiphospholipid syndrome. The primary objective of this article is to describe scientific advances in the study of the antiphospholipid syndrome, current classification criteria, the role of anticardiolipin antibodies, anti-β2 glycoprotein I and lupus anticoagulant, and to describe the pathogenic and immunological mechanisms in which these antibodies are involved. Furthermore, this article describes some of the associated clinical and diagnostic procedures currently used for antiphospholipid syndrome identification.

Anticorpos antinucleossomo e síndrome antifosfolipídica: estudo observacional / Antinucleosome antibodies and primary antiphospholipid syndrome: an observational study

OBJETIVO: Avaliar a associação entre a presença de anticorpos antinucleossomo (anti-NCS) e a síndrome antifosfolipídica primária (SAFP) e o posterior desenvolvimento de lúpus eritematoso sistêmico (LES). MATERIAIS E MÉTODOS: Trinta e seis mulheres com o diagnóstico de SAFP foram avaliadas prospectivamente para manifestações de doenças reumáticas autoimunes e para a presença de anticorpos antifosfolípides, anticorpos antinucleares e anti-NCS/cromatina. RESULTADOS: Após um período médio de seguimento de 45,7 meses, anticorpos anti-NCS/cromatina foram detectados em apenas uma paciente (2,8%), que desenvolveu manifestações de LES tais como poliartrite, linfopenia, neurite óptica, lesões compatíveis com esclerose múltipla em substância branca cerebral e perfil de autoanticorpos altamente sugestivo de LES. CONCLUSÃO: A frequência de anticorpos anti-NCS/cromatina é baixa em pacientes com SAFP, e sua presença pode associar-se ao desenvolvimento de manifestações de LES.

OBJECTIVE: To study the association of anti-nucleosome (anti-NCS) antibodies in primary antiphospholipid syndrome (APS) and the development of systemic lupus erythematosus (SLE) during follow-up. MATERIALS AND METHODS: Thirty-six women with primary APS were evaluated prospectively for clinical features of systemic autoimmune diseases and for the presence of antiphospholipid antibodies, antinuclear antibodies and anti-NCS/chromatin antibodies. RESULTS: After a mean follow-up period of 45.7 months, anti-NCS/chromatin antibodies were detected in only one patient (2.8%), who developed features of SLE including polyarthritis, lymphopenia, optic neuritis, multiple sclerosis-like lesions, and an autoantibody profile suggestive of SLE. CONCLUSION: The frequency of anti-NCS/chromatin antibodies in primary APS patients is very low, and they may be associated with the development of SLE manifestations.

Abordagem laboratorial das síndromes antifosfolípide e do aborto recorrente / Laboratories analyses indicated in antiphospholipid and recurrent abortion syndrome

Um aumento no potencial hemostático endometrial ocorre durante o ciclo menstrual, possibilitando, assim, a implantação embrionária, caso ocorra a fertilização. Defeitos nas proteínas de coagulação podem alterar esse estado de hipercoagulabilidade gestacional e desencadear perdas fetais por falhas na implantação ou na nutrição do embrião. A síndrome do aborto recorrente pode ser ocasionada por inúmeros fatores, entre eles anormalidades cromossômicas, anatômicas ou hormonais, ou ainda por defeitos nas proteínas de coagulação sanguínea ou plaquetária. Uma causa comum de abortos recorrentes é a síndrome antifosfolípide, uma desordem sistêmica, autoimune, caracterizada por trombose arterial e/ou venosa, morte fetal, abortos recorrentes e trombocitopenia, acompanhada de títulos elevados de anticorpos antifosfolípides: anticoagulante lúpico e/ou anticardiolipina. Pela íntima associação dessas síndromes, faz-se necessário investigá-las em pacientes que procuram os tratamentos de fertilização in vitro.

An increase in endometrial hemostatic potential occurs during the menstrual cycle, thus enabling the embryonic implantation in the occurrence of fertilization. Defects in the coagulation proteins may change this state of gestational hypercoagulability and cause fetal losses by failures in the implantation or nutrition of the embryo. The recurrent abortion syndrome can occur by many factors, including chromosomal, anatomical or hormonal abnormalities or defects in proteins of blood or platelet coagulation. A common cause of recurrent miscarriages is antiphospholipid syndrome, a systemic disorder, autoimmune, characterized by arterial and/or venous thrombosis, fetal death, recurrent miscarriages, and thrombocytopenia, accompanied by evidence of elevated antiphospholipid antibodies: lupus anticoagulant and/or anticardiolipin. Due to the intimate association of these syndromes, the investigation of them is necessary in patients seeking for in vitro fertilization treatment.