Diferencias en la conclusión final de la búsqueda de anticoagulante lúpico en pacientes anticoagulados con antagonistas de la vitamina K / Differences in the final conclusion of the search for lupus anticoagulant in patients anticoagulated with vitamin K antagonists

Resumen Introducción. La detección de anticoagulante lúpico (AL) en pacientes que reciben el tratamiento con antagonistas de la vitamina K (AVK) es todavía una asignatura pendiente. Algunas guías recomiendan realizar todas las pruebas en la mezcla equimolar del plasma del paciente y el pool de plasmas normales (PN+PP), en aquellos pacientes con RIN<3. Sin embargo, la última guía de la ISTH sugiere no determinar AL en pacientes con AVK. Objetivo. Comparar la conclusión final de los estudios de AL, realizando las pruebas de tamizaje y confirmatorias en el plasma puro (PP) y en la mezcla (PP+PN), en pacientes en tratamiento con AVK. Población. 90 pacientes con diagnóstico previo de AL persistente, que al momento de su inclusión estaban en tratamiento con AVK con RIN < 3. Todos habían sido estudiados por segunda vez para confirmar el diagnóstico de AL persistente, a los tres meses, bajo tratamiento anticoagulante con heparina de bajo peso molecular y luego continuaron con el tratamiento con AVK. Materiales y métodos. Se realizaron los ensayos de tamizaje y confirmatorio del tiempo de veneno de víbora de Russell (dRVVT y cRVVT) y del tiempo de coagulación de sílice (sSCT y cSCT). Se preparó el pool de plasmas normales con 40 donantes de sangre, que fueron negativos para la evaluación de AL. Los puntos de corte fueron establecidos localmente de acuerdo a la guía ISTH. Resultados. 33/90 pacientes fueron AL positivo tanto en PP como en PP+PN, 27 negativos y 30 discordantes. 46 de las 90 muestras fueron positivas por dRVVT en PP, pero sólo 18/90 fueron positivas por ensayo de dRVVT en PP+PN. El valor de kappa para la medida de la concordancia entre el ensayo dRVVT en ambas situaciones fue de 0,21 (IC del 95 % = 0,047-0,374). 52/90 fueron negativos por ensayo SCT en PP y 50/90 fueron negativos en PP+PN. 31/90 fueron positivos en ambos casos. Sólo 9/90 fueron positivos por SCT en PP+PN y negativos en PP. El índice kappa para el SCT fue 0,64 (0,431-0,844). Discusión. Aunque realizar las pruebas de AL en PP+PN en pacientes anticoagulados con AVK es una práctica habitual, de acuerdo con estos resultados no es una buena opción, porque podría dar un diagnóstico falsamente negativo o positivo, dependiendo del ensayo. La discrepancia entre usar o no la mezcla es mayor en el ensayo de Drvvt.

Abstract Introduction. The detection of lupus anticoagulant (LA) in patients who are on vitamin K antagonist (VKA) treatment is still an unresolved issue. Some guidelines recommend performing all tests on the equimolar mixture of the patient's plasma plus normal plasma pool (PN+PP) in those patients with INR<3. However, the latest ISTH guideline suggests not determining LA in patients with VKA. AIM. To compare the final conclusion of LA studies, performing screening and confirmatory tests in pure plasma (PP) and in the mixture (PP+PN), in patients receiving VKA treatment. Population. 90 patients with a previous diagnosis of persistent AL, who at the time of inclusion were in treatment with VKA with INR < 3. All had been studied for a second time to confirm the diagnosis of persistent LA, three months later, under anticoagulant treatment with low molecular weight heparin and then continued treatment with VKA. Materials and methods. Screening and confirmatory tests of Russell's viper venom time (dRVVT and cRVVT) and silica coagulation time (sSCT and cSCT) were performed. The normal plasma pool was prepared with 40 blood donors, who were negative for the AL evaluation. The cut-off points were established locally according to the ISTH guideline. Results. 33/90 patients were LA positive considering PP and PP+PN, 27 were negative and 30 discordant. 46 of the 90 samples were positive by dRVVT in PP but only 18/90 were positive by dRVVT assay in PP+PN. The kappa value for the measure of agreement between the dRVVT test in both situations was 0.21 (95% CI = 0.047-0.374). 52/90 were negative by SCT assay in PP and 50/90 were positive in PP+PN. Only 9/90 were positive by SCT in PP+PN and negative in PP. The kappa index for the SCT was 0.638 (0.431-0.844). Discussion. Although performing LA tests on the PP+PN mixture in anticoagulated patients with VKA is a common practice, according to these results, it is not a good option because they could give a false negative or positive diagnosis, depending on the assay. The discrepancy between using or not using the mixture is greater in dRVVT´s assay.

Síndrome antifosfolipídico trombótico en una mujer con enfermedad mixta del tejido conectivo. Reporte de caso / Thrombotic antiphospholipid syndrome in a woman with mixed connective tissue disease. Case report

Introducción: El síndrome de anticuerpos antifosfolípidos es una enfermedad au-toinmune sistémica poco frecuente, produce hipercoagulabilidad con riesgo de trombosis. Para el diagnóstico se utilizan los criterios ACR/EULAR APS del 2023. El tratamiento es anticoagulantes y antiagregantes plaquetarios. La enfermedad mixta del tejido conectivo es enfermedad autoinmunitaria sistémica con la asociación de manifestaciones clínicas de otras entidades autoinmunes. Objetivo:Describir la presentación de dos enfermedades sistémicas autoinmunes poco frecuentes en conjunto, con el propósito de contribuir con un enfoque prác-tico para el diagnóstico y manejo. Presentación del caso: Se describe una paciente de 37 años que presentó un episodio de tromboembolia pulmonar secundario a síndrome de anticuerpos anti-fosfolípidos y en los 6 meses previos tuvo síntomas compatibles con enfermedad mixta del tejido conectivo. Discusión: La presencia de dos entidades autoinmunes, síndrome de anticuerpos antifosfolípidos y enfermedad mixta del tejido conectivo presentadas en conjunto y cuyo debut de complicaciones fue una tromboembolia pulmonar, encontrándo-se presencia de múltiples autoanticuerpos positivos entre estas anticuerpos an-tifosfolipídicos y anti-U1 snRNP, es un reto diagnóstico al diferenciar entre otras enfermedades del tejido conectivo como lupus eritematoso sistémico, esclerosis sistémica cutánea, enfermedad mixta del tejido conectivo y artritis reumatoide. El tratamiento se basó en las características del paciente y su condición clínica al momento del diagnóstico. Conclusiones: El síndrome de anticuerpos antifosfolipídicos conlleva la presencia de un episodio trombótico, por otro lado, su asociación con una enfermedad mixta del tejido conectivo es poco frecuente y puede aumentar su morbimortalidad.

Introduction: Antiphospholipid antibody syndrome is a rare systemic autoimmu-ne disease that produces Antiphospholipid antibody syndrome is a rare systemic autoimmune disease that causes hypercoagulability with risk of thrombosis. For diagnosis, the ACR/EULAR APS 2023 criteria are used. Treatment is anticoagulants and antiplatelet agents.Mixed connective tissue disease is a systemic autoimmune disease with the asso-ciation of clinical manifestations of other autoimmune entities.Objective:To describe the presentation of two rare autoimmune systemic diseases toge-ther, with the purpose of contributing a practical approach to diagnosis and management.Case presentation: 37-year-old patient with an episode of pulmonary thromboem-bolism secondary to antiphospholipid antibody syndrome and in the previous 6 months he had symptoms compatible with mixed connective tissue disease.Discussion:The presence of two autoimmune entities, antiphospholipid antibody syndrome and mixed connective tissue disease presented together and whose de-but of complications was a pulmonary thromboembolism, finding the presence of multiple positive autoantibodies between these antiphospholipid antibodies and an-ti-U1 snRNP, is a diagnostic challenge in differentiating between other connective tissue diseases such as systemic lupus erythematosus, cutaneous systemic sclero-sis, mixed connective tissue disease and rheumatoid arthritis. Treatment was based on the patient's characteristics and clinical condition at the time of diagnosis.Conclusions: Antiphospholipid antibody syndrome entails the presence of a thrombotic episode; on the other hand, its association with a mixed connective tissue disease is rare and may increase its morbidity and mortality.

Analyses of the risk factors for the progression of primary antiphospholipid syndrome to systemic lupus erythematosus / 中华内科杂志

Objectives:Analyze the clinical characteristics of patients with primary antiphospholipid syndrome (PAPS) progressing to systemic lupus erythematosus (SLE).Explore the risk factors for the progression from PAPS to SLE.Methods:The clinical data of 262 patients with PAPS enrolled in Peking Union Medical College Hospital from February 2005 to September 2021 were evaluated. Assessments included demographic data, clinical manifestations, laboratory tests (serum levels of complement, anti-nuclear antibodies, anti-double-stranded DNA antibodies), treatment, and outcomes. Kaplan-Meier analysis was used to calculate the prevalence of SLE in patients with PAPS. Univariate Cox regression analysis was employed to identify the risk factors for PAPS progressing to SLE.Results:Among 262 patients with PAPS, 249 had PAPS (PAPS group) and 13 progressed to SLE (5.0%) (PAPS-SLE group). Univariate Cox regression analysis indicated that cardiac valve disease ( HR=6.360), positive anti-double-stranded DNA antibodies ( HR=7.203), low level of complement C3 ( HR=25.715), and low level of complement C4 ( HR=10.466) were risk factors for the progression of PAPS to SLE, whereas arterial thrombotic events ( HR=0.109) were protective factors ( P<0.05 for all). Kaplan-Meier analysis showed that the prevalence of SLE in patients suffering from PAPS with a disease course>10 years was 9%-15%. Hydroxychloroquine treatment had no effect on the occurrence of SLE in patients with PAPS ( HR=0.753, 95% CI 0.231-2.450, P=0.638). Patients with≥2 risk factors had a significantly higher prevalence of SLE compared with those with no or one risk factor (13-year cumulative prevalence of SLE 48.7% vs. 0 vs. 6.2%, P<0.001 for both). Conclusions:PAPS may progress to SLE in some patients. Early onset, cardiac-valve disease, positive anti-dsDNA antibody, and low levels of complement are risk factors for the progression of PAPS to SLE (especially in patients with≥2 risk factors). Whether application of hydroxychloroquine can delay this transition has yet to be demonstrated.

Analysis of anticoagulant therapy and pharmaceutical care for a patient with obstetrical antiphospholipid syndrome complicated with HELLP syndrome / 药物流行病学杂志

A 37-year-old woman with obstetric antiphospholipid syndrome(OAPS)was admitted to hospital due to poorly controlled hypertensive.After admission,the patient's blood pressure fluctuated greatly(152-161/100-112mmHg),platelet count decreased progressively(65x109·L-1),with lactate dehydrogenase of 367 U·L-1,alanine aminotransferase of 121.8 U·L-1,and aspartate aminotransferase of 89 U·L-1,and the disease progressed to HELLP syndrome.The clinical pharmacists participated in the treatment of this patient,combined the patient's risk of thrombosis and bleeding,changes in platelet count,and pharmacokinetic characteristics of anticoagulant drugs to assist clinicians in formulating the individualized anticoagulant treatment plan in the perinatal period,and promptly stopped and started anticoagulant drugs,which effectively prevented the patient from the occurrence of thrombosis and postpartum hemorrhage complications.Meanwhile,based on evidence-based pharmacology,the clinical pharmacists analyzed the key points of pharmacological care for such patients during pregnancy and lactation.The standardized use of OAPS treatment drugs,such as hydroxychloroquine,aspirin and prednesone,have more advantages than disadvantages during pregnancy,but the corresponding adverse reactions need to be closely monitored.Enoxaparin does not accumulate in milk and can be used safely during lactation.The clinical pharmacists play an important role in guaranteeing the safety and effectiveness of medication for pregnant and lactation patients.

Research Update on the Phenotype of Cardiovascular Diseases Associated With Antiphospholipid Syndrome / 中国循环杂志

Antiphospholipid syndrome is a systemic autoimmune disease characterized by recurrent thrombotic events,pregnancy complications and persistent positive antiphospholipid antibodies.As a systemic disease,antiphospholipid syndrome can affect multiple organs and systems,including the cardiovascular system.Antiphospholipid syndrome-related cardiovascular diseases can cause serious threats to patients'lives.In the updated ACR/EULRA classification criteria for antiphospholipid syndrome issued in 2023,valvular disease has been included in the clinical criteria of antiphospholipid syndrome,which highlights the importance of considering cardiovascular diseases associated with antiphospholipid syndrome.This article reviews the research progress on the phenotype and mechanisms of cardiovascular diseases associated with antiphospholipid syndrome.

Experiencing pregnancy in the context of lupus and antiphospholipid syndrome: a grounded theory / Experimentando el embarazo en el contexto del lupus y del síndrome antifosfolípido: una teoría fundamentada / Vivenciando a gestação no contexto do lúpus e da síndrome antifosfolípide: uma teoria fundamentada

ABSTRACT Objective: To understand the meanings attributed to pregnancy in the context of Lupus and antiphospholipid syndrome by women and healthcare professionals. Method: Qualitative research, using Symbolic Interactionism as a theoretical framework and Grounded Theory, a constructivist perspective. Data were collected between January and August 2022, through online interviews with 27 women with Lupus located on the social network Facebook and in-person or remote interviews with 12 healthcare professionals. Results: The theoretical model constructed has two categories: "Equal conditions, distinct experiences: experiencing the gestational process" shows that obstetric complications and lack of connection with healthcare professionals trigger negative meanings to the experience; and "Therapeutic management interfering in the attribution of meanings to the experience", demonstrates that the way women interact with healthcare professionals and how they manage treatment favors a positive reframing. Final considerations: The meanings attributed to pregnancy are elaborated and modified according to the interpretation of previous and current experiences, healthcare trajectory and interactions with healthcare professionals. Previous guidance, planning, bonding and trust in healthcare professionals enable positive meanings, while obstetric complications, unqualified assistance and lack of bonding with professionals provide negative meanings.

RESUMEN Objetivo: Comprender los significados atribuidos al embarazo en el contexto del Lupus y del síndrome antifosfolípido por mujeres y profesionales de la salud. Método: Investigación cualitativa, que utilizó como marco teórico el Interaccionismo simbólico y metodológico, la Teoría Fundamentada, una vertiente constructivista. Los datos fueron recolectados entre enero y agosto de 2022, a través de entrevistas online a 27 mujeres con Lupus ubicadas en la red social Facebook y entrevistas presenciales o remotas a 12 profesionales de la salud. Resultados: El modelo teórico construido tiene dos categorías: "Condiciones iguales, experiencias diferentes: vivir el proceso gestacional" muestra que las complicaciones obstétricas y la falta de conexión con los profesionales de la salud desencadenan significados negativos a la experiencia; y Gestión terapéutica interfiriendo en la atribución de significados", demuestra que la forma en que las mujeres interactúan con los profesionales de la salud y cómo conducen el tratamiento favorece la resignificación positiva.. Consideraciones finales: Los significados atribuidos al embarazo son elaborados y modificados según la interpretación de experiencias pasadas y actuales, trayectoria de atención e interacciones con profesionales de la salud. La orientación previa, la planificación, la vinculación y la confianza en los profesionales de la salud posibilitan significados positivos, mientras que las complicaciones obstétricas, la asistencia no calificada y la falta de vínculo con los profesionales proporcionan significados negativos.

RESUMO Objetivo: Compreender os significados atribuídos à gravidez, no contexto do Lúpus e da Síndrome Antifosfolípide, por mulheres e profissionais de saúde. Método: Pesquisa qualitativa, que utilizou como referencial teórico o Interacionismo simbólico e metodológico, a Teoria Fundamentada nos Dados, vertente construtivista. Os dados foram coletados entre janeiro e agosto de 2022, mediante entrevistas on-line com 27 mulheres com Lúpus, localizadas na rede social Facebook e em entrevistas presenciais ou remotas com 12 profissionais de saúde. Resultados: O modelo teórico construído possui duas categorias: "Condições iguais, experiências distintas: vivenciando o processo gestacional" mostra que complicações obstétricas e ausência de vínculo com os profissionais de saúde desencadeiam significados negativos à experiência; e "O manejo terapêutico interferindo na atribuição dos significados à experiência" demonstra que a forma com que a mulher interage com os profissionais de saúde e conduz o tratamento favorece a ressignificação positiva. Considerações finais: Os significados atribuídos à gestação são elaborados e modificados conforme a interpretação de experiências anteriores e atuais, trajetória assistencial e interações com os profissionais de saúde. A orientação prévia, o planejamento, o vínculo e a confiança nos profissionais de saúde possibilitam significados positivos. Já, as complicações obstétricas, a assistência não qualificada e ausência de vínculo com os profissionais produzem significados negativos.

Retinal vein and artery occlusion as the first manifestation of primary antiphospholipid syndrome in a pediatric patient / Oclusão arterial e venosa como primeira manifestação da síndrome antifosfolipide primária em criança

ABSTRACT Antiphospholipid syndrome is an acquired autoimmune disease characterized by hypercoagulability associated with recurrent venous and arterial thromboembolism in the presence of antiphospholipid antibodies. Herein, we report a case of rapid sequential retinal vein and artery occlusion as the first manifestation of a primary antiphospholipid syndrome triggered by an acute Mycoplasma infection in a previously healthy 11-year-old patient. On day 1, ophthalmoscopy revealed a central retinal vein occlusion. The patient developed temporal branch retinal artery occlusion the next day. On day 3, a central retinal artery occlusion was observed. Serum lupus anticoagulant, immunoglobulin (Ig) G anticardiolipin, IgG anti-β2-glycoprotein 1 antibody, and Mycoplasma pneumoniae IgM antibody levels were increased. Thus, retinal vascular occlusions can be the first manifestation of primary antiphospholipid syndrome. Although it may not improve visual prognosis, prompt diagnosis and treatment are essential to avoid further significant morbidity.

RESUMO A síndrome antifosfolipide é uma doença autoimune adquirida caracterizada por hipercoagulabilidade associada a tromboembolismo venoso e arterial recorrente na presença de anticorpos antifosfolipídicos. Aqui, relatamos um caso clínico de oclusão sequencial de veia e artéria da retina como primeira manifestação de uma síndrome antifosfolipíde primária desen­cadeada por uma infeção aguda por Mycoplasma num paciente de 11 anos previamente saudável. No primeiro dia, a oftalmoscopia revelou uma oclusão da veia central da retina. No dia seguinte, o paciente desenvolveu uma oclusão do ramo temporal da artéria central da retina. No terceiro dia, uma oclusão da artéria central da retina foi diagnosticada. Os níveis de anticoagulante lúpico sérico, anticorpos IgG anticardiolipina e IgG anti-β2-glicoproteína 1 e anticorpos IgM para Mycoplasma pneumoniae estavam aumentados. As oclusões vasculares retinianas podem ser a primeira manifestação da síndrome antifosfolipíde primária. Apesar do prognóstico visual ser reservado, o seu diagnóstico e o tratamento imediatos são essenciais para evitar outras morbilidades associadas.

Presentación atípica de síndrome antifosfolípido

El síndrome antifosfolípido es considerado un trastorno del colágeno asociado a presentaciones clínicas a edades intermedias con incidencias no mayores de 5 casos por cada 100.000 personas. Su espectro clínico oscila en la presencia de manifestaciones trombóticas multisistémicas de origen vascular. Sin embargo, las manifestaciones no vasculares tienen un espectro raro en su presentación habitual. Se presenta el caso de un varón de 64 años con manifestaciones oculares relacionadas a amaurosis fugaz asociado a alteraciones estructurales retinianas. Los hallazgos de tamizajes realizados fueron fuertemente sugestivos de trombofilias primarias. Se aplicó perfil para síndrome antifosfolípido el cual fue positivo, por lo que se instauró anticoagulación plena.

Antiphospholipid syndrome is considered a collagen disorder associated with clinical presentations at intermediate ages with incidences of no more than 5 cases per 100,000 people. Its clinical spectrum ranges from the presence of multisystem thrombotic manifestations of vascular origin. However, non-vascular manifestations have a rare spectrum in their usual presentation. The case of a 64-year-old man with ocular manifestations related to amaurosis fugax associated with retinal structural alterations is presented. The findings of screening performed were strongly suggestive of primary thrombophilia. A profile for antiphospholipid syndrome was applied, which was positive and therefore, full anticoagulation was initiated.

Factores de predicción relevantes en la supervivencia de pacientes con síndrome antifosfolípido / Relevants predictions factors in the survival of patients with antiphospholipid syndrome

Introducción: Los pacientes con síndrome antifosfolípido desarrollan morbilidad y mortalidad significativas a pesar del tratamiento actual. Es imperativo, identificar factores pronósticos y medidas terapéuticas para prevenir estas complicaciones. Objetivo: Determinar los factores relevantes en la predicción de la supervivencia en los pacientes con síndrome antifosfolípido. Métodos: Se realizó un estudio longitudinal analítico de una cohorte histórica de personas con síndrome antifosfolípido, diagnosticados, según los criterios de Sapporo/Sydney y colaboradores en la consulta de enfermedades autoinmunes sistémicas del Hospital Universitario Clínico-Quirúrgico «Arnaldo Milián Castro», Villa Clara, del año 2000 al 2015. Se estudiaron variables demográficas y clínicas. En cada caso se determinó el tiempo de supervivencia con relación al evento muerte. Se aplicó el método de Kaplan Meier para calcular la supervivencia global y determinar las variables predictoras de la mortalidad. Según el estudio de los estadígrafos de comparación interestratos(Log-Rank) se demostró la significación estadística con la prueba de Chi cuadrado de homogeneidad. Resultados: De los 128 pacientes estudiados, 118 fueron femeninos y 10 masculinos (111 de piel blanca y 17 no blancos). La supervivencia global fue de 67,1 % con una media de 13,37 años. Las variables más relevantes que aportaron a la mortalidad en relación con menor supervivencia fueron: leucopenia, linfopenia, color de la piel no blanca, y el no uso de aspirina, con medias de supervivencia de 8,83; 8,17; 10,72; 12,10 años, respectivamente. Conclusiones: La identificación temprana de los factores pronósticos de supervivencia permite implementar estrategias oportunas e individualizadas en pacientes con síndrome antifosfolípido.

Introduction: patients with antiphospholipid syndrome develop significant morbidity and mortality despite current treatment. Identifying prognostic factors and therapeutic measures to prevent these complications is indispensable. Objective: to determine relevant factors in the prediction of survival in patients with antiphospholipid syndrome. Methods: a longitudinal analytical study was carried out on cohorts with antiphospholipid syndrome who were diagnosed according to the Sapporo-Sydney criteria and collaborators in the systemic autoimmune disease consultation at "Arnaldo Milián Castro" Clinical and Surgical University Hospital in Villa Clara from 2000 to 2015. Demographic and clinical variables were studied. The survival time in relation to the death event was determined in each case. The Kaplan - Meier method was applied to calculate overall survival and determine the predictor variables for mortality. According to the study of inter-strata comparison statistics (Log-Rank), statistical significance was demonstrated with the Chi-square test of homogeneity. Results: a number of 118 patients were female and 10 male from the 128 studied (111 white-skinned and 17 non-white). Overall survival was 67.1% with a mean of 13.37 years. The most relevant variables that contributed to mortality in relation to lower survival were leukopenia, lymphopenia, non-white skin color and non-use of aspirin, with mean survival of 8.83; 8.17; 10.72; 12.10 years, respectively. Conclusions: the early identification of survival prognostic factors allows us the implementation of timely and individualized strategies in patients with antiphospholipid syndrome.

As trombofilias na perda gestacional de repetição: uma revisão de prevalência e condutas / Thrombophilias in recurrent pregnancy loss: a review of prevalence and conduct

Objetivo: Discutir o papel das trombofilias na perda gestacional de repetição, com foco em prevalência/associação dessas patologias com perdas de repetição e seu tratamento, por meio de resultados de ensaios clínicos, revisões sistemáticas e metanálises. Métodos: Trata-se de uma revisão não sistemática de artigos publi- cados nas bases eletrônicas PubMed, Cochrane e SciELO nos últimos cinco anos, utilizando os seguintes descritores: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome" e "treatment". Resultados: A maioria dos estudos relatou forte associação entre os anticorpos antifosfolípides específicos e a síndrome do anticorpo antifosfolípide com perda gestacional de repetição. Mulheres portadoras da mutação do fator V de Leiden, mutação do gene da protrombina e deficiência de proteína S apresentaram alto risco de perda gestacional de repetição em uma grande revisão sistemática. Estudos recentes demonstraram taxas de prevalência das trombofilias hereditárias e da síndrome do anticorpo antifosfolípide, em mulheres com perda gestacional de repetição, semelhantes às da população em geral. Os estudos atuais endossam o uso da heparina associada à aspirina em mulheres com síndrome do anticorpo antifosfolípide, com aumento da taxa de nascidos vivos, mas sem diferença em re- lação às complicações obstétricas. Conclusão: Apesar de novos estudos demons- trarem que a prevalência das trombofilias hereditárias e adquiridas em mulheres com perda gestacional de repetição é semelhante à da população em geral, reco- menda-se a pesquisa rotineira de síndrome do anticorpo antifosfolípide nessas pacientes. O uso de aspirina em baixas doses associada à heparina é a intervenção farmacológica de primeira linha para a prevenção de perda gestacional de repeti- ção em pacientes com síndrome do anticorpo antifosfolípide.

Objective: To discuss the role of thrombophilias in recurrent pregnancy loss, focu- sing on the prevalence/association of these pathologies with recurrent abortion and treatment, through results of clinical trials, systematic reviews and meta-analyses. Methods: This is a non-systematic review of articles published in electronic databa- ses PubMed, Cochrane, SciELO in the last five years, using the following descriptors: "recurrent pregnancy loss", "recurrent abortion", "habitual abortion", "thrombophilia", "antiphospholipid syndrome", and "treatment". Results: Most studies have reported a strong association between specific antiphospholipid antibodies and antiphospho- lipid antibody syndrome with recurrent pregnancy loss. Women carrying the factor V Leiden mutation, prothrombin gene mutation, and protein S deficiency were shown to be at high risk of recurrent pregnancy loss in a large systematic review. Recent studies have shown prevalence rates of hereditary thrombophilias and antiphospholipid antibody syndrome, in women with re- current pregnancy loss, similar to those of the general po- pulation. Current studies endorse the use of heparin plus aspirin in women with antiphospholipid antibody syndrome, with an increase in live birth rate, but with no difference in obstetric complications. Conclusion: Although new studies demonstrate that the prevalence of hereditary and acquired thrombophilias in women with recurrent pregnancy loss is si- milar to that of the general population, routine investigation of antiphospholipid antibody syndrome in these patients is recommended. The use of low-dose aspirin plus heparin is the first-line pharmacological intervention for the prevention of recurrent pregnancy loss in patients with antiphospholipid antibody syndrome.

Infarto pulmonar cavitado en mujer con lupus eritematoso sistémico asociado a síndrome antifosfolípido

Tanto lupus eritematoso sistémico como el síndrome antifosfolípido son enfermedades autoinmunes con potencial tromboembólico, sobre todo por la presencia de anticuerpos trombogénicos. El pulmón es un lugar común donde suele asentarse un trombo y generar una tromboembolia, a veces con posterior infarto y cavitación. Existen pocos estudios que informen un infarto pulmonar cavitado en un paciente con lupus asociado a síndrome antifosfolípido. Presentamos el caso de una mujer de 24 años con síntomas generales y lesión pulmonar derecha cavitada. Fue tratada inicialmente como infección tuberculosa o fúngica. La analítica y las imágenes orientaron y diagnosticaron lupus asociado a síndrome antifosfolípido, complicado con tromboembolismo pulmonar que luego pasó a cavitarse. La paciente mejoró considerablemente con anticoagulantes, corticoides y ciclofosfamida.

Both systemic lupus erythematosus and antiphospholipid syndrome are autoimmune diseases with thromboembolic potential, especially due to the presence of thrombogenic antibodies. The lung is a common place where a thrombus usually settles and generates a thromboembolism, sometimes with subsequent infarction and cavitation. There are few studies reporting cavitary pulmonary infarction in a patient with lupus associated with antiphospholipid syndrome. We present the case of a 24-year-old woman with general symptoms and cavitated right lung lesion. She was initially treated as tuberculous or fungal infection. Laboratory tests and images guided and diagnosed lupus associated with antiphospholipid syndrome, complicated by pulmonary thromboembolism that later became cavitated. The patient improved considerably with anticoagulants, corticosteroids, and cyclophosphamide.

Complicaciones hemorrágicas y trombóticas del embarazo: diagnóstico, prevención y tratamiento

Las hemorragias y la enfermedad tromboembólica venosa (ETEV) figuran entre las cinco causas más frecuentes de morbilidad y mortalidad materna en el mundo. Revisamos la evaluación y el manejo actualizado de las causas obstétricas de la hemorragia posparto (HPP), así como el diagnóstico y manejo de condiciones hematológicas que pueden causar o agravar la HPP, por ejemplo: coagulación intravascular diseminada, enfermedad de von Willebrand, trombocitopenia autoinmune y las microangiopatías trombóticas. Revisamos el rol del síndrome antifosfolípido y las trombofilias hereditarias como factores predisponentes a pérdidas fetales recurrentes y la ETEV en el embarazo y las recomendaciones actuales para la prevención de ambas complicaciones. Asimismo, repasamos el abordaje diagnóstico y líneas de manejo de la ETEV. Un objetivo adicional fue enfatizar la importancia del trabajo colaborativo multidisciplinario para lograr el manejo exitoso de las gestantes con las complicaciones obstétricas y hematológicas descritas.

Bleeding and venous thromboembolism (VTE) are among the five most common causes of morbidity and mortality in pregnant women worldwide. This review describes the current evaluation and management of the obstetric causes of postpartum hemorrhage (PPH), as well as the diagnosis and management of hematologic conditions which can cause or worsen PPH, such as disseminated intravascular coagulation, von Willebrand disease, autoimmune thrombocytopenia and the thrombotic microangiopathies. It also describes the role of the antiphospholipid syndrome and inherited thrombophilia as predisposing factors for recurrent pregnancy loses and VTE, and the current recommendations for the prevention of both complications. As well, the current diagnostic approach and management of ETEV are described. An additional objective of this Review is to emphasize the importance of a collaborative multidisciplinary approach for the successful management of the obstetric and hematologic complications herein described.

Síndrome antifosfolípido y tumores cardiacos

Presentamos el caso de una paciente mujer de 31 años con antecedente de litiasis coraliforme bilateral. Ella inició la enfermedad un mes antes del ingreso con trombocitopenia y anemia hemolítica autoinmune. Fue diagnosticada con Síndrome de Evans, inicialmente tuvo marcadores de autoinmunidad negativos, finalmente presentó disnea progresiva y se le encontró 4 masas intracardiacas en aurícula derecha y marcadores positivos para síndrome antifosfolípido. A pesar de la anticoagulación y preparación para cirugía cardiaca, la paciente tuvo una muerte súbita.

We present the case of a 31-year-old female patient with a history of bilateral staghorn lithiasis, who started the disease one month before admission with thrombocytopenia and autoimmune hemolytic anemia. She was diagnosed with Evans Syndrome, initially she had negative autoimmunity markers, finally presented progressive dyspnea and 4 intracardiac masses were found in the right atrium and positive markers for antiphospholipid syndrome. Despite anticoagulation and preparation for cardiac surgery, she presented sudden death.

Systemic Lupus Erythematosus Combined with Chorea: Report of One Case and Literature Review / 中国医学科学院学报

Systemic lupus erythematosus combined with chorea is relatively rare in China,and there are no unified diagnostic criteria or specific ancillary tests.Therefore,it is confirmed by exclusionary clinical diagnosis.To improve the understanding of this disease among rheumatologists,we report the clinical data of a patient with systemic lupus erythematosus combined with chorea admitted to the Department of Rheumatology and Immunology in the First Affiliated Hospital of Jinan University in January 2022.Furthermore,we review the relevant literature in the past 10 years and summarize the clinical features of these cases.

Advances in the Effects of Antiphospholipid Syndrome on Female Infertility and Outcomes of Assisted Reproductive Technologies / 中山大学学报(医学科学版)

Antiphospholipid syndrome （APS） is an autoimmune disease characterized by the persistent presence of antiphospholipid antibodies， which are associated with thrombosis and pregnancy-related complications. APS may have adverse effects on female reproductive function by affecting ovarian function， endometrialization， and other mechanisms， and may lead to embryo implantation failure and pregnancy loss during in vitro fertilization and embryo transfer （IVF-ET） treatments. The routine screening and management of APS before IVF-ET in infertile populations remains controversial and requires individualized risk assessment and appropriate management measures to improve the success rate of assisted reproductive technologies （ART） and reduce maternal and fetal risks during pregnancy. This review summarizes the effects of APS on female infertility and outcomes of ART， as well as the management of the population affected by APS， providing new insights for clinical diagnosis and treatment.

Predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome / 北京大学学报(医学版)

OBJECTIVE@#To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome.@*METHODS@#A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People's Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis.@*RESULTS@#Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%.@*CONCLUSION@#TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.

Myocardial performance index for evaluating fetal left ventricular function in pregnant women with obstetric antiphospholipid syndrome / 中国医学影像技术

Objective To observe the value of myocardial performance index(MPI)for evaluating fetal left ventricular(LV)function in pregnant women with obstetric antiphospholipid syndrome(OAPS).Methods Totally of 41 singleton pregnancy women with OAPS(criteria-OAPS[C-OAPS]group,n=16;non-criteria OAPS[NC-OAPS]group,n=25)and 60 healthy singleton pregnancy women(control group)were prospectively enrolled.Mitral flow E velocities/A velocities,isovolumic relaxation time(IRT),isovolumic contraction time(ICT),ejection time(ET)and MPI of fetal LV were compared among 3 groups.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of MPI for predicting adverse pregnancy outcomes of pregnant woman.Results Significant differences of mitral flow E velocities/A velocities,IRT,ICT,ET and MPI of fetal LV were found among 3 groups(all P＜0.05).Results of pairwise comparison showed that among C-OAPS group,NC-OAPS group and control group,IRT and MPI of LV decreased,whereas E/A and ET of LV increased in order(all P＜0.05).ICT in C-OAPS group was higher than that in control group(P＜0.05).The sensitivity,specificity and area under the curve of MPI for predicting adverse pregnancy outcomes of pregnant woman with OAPS was 90.00％,64.45％and 0.798,respectively.Conclusion MPI could be used to evaluate fetal LV function in pregnant women with OAPS,also being helpful for predicting adverse pregnancy outcomes.

Risk factors of cerebral infarction in patients with primary antiphospholipid syndrome / 中华风湿病学杂志

Objective:To analyze the clinical manifestations, risk factors and risk of recurrence in patients with primary antiphospholipid syndrome (PAPS) complicated with cerebral infarction.Methods:Inpatients diagnosed with PAPS was recruited between 2010 and 2020. Clinical characteristics,laboratory results and adjusted global antiphospholipid syndrome score (aGAPSS) were compared between patients with cerebral infarction and without cerebral infarction by χ2 test, t test or Mann-Whitney U test. Univariate and multivariate Logistic analysis were performed to identify the risk factors associated with cerebral infarction. Results:In 145 PAPS patients [median age 44.0 (34.0, 51.5) years, 66.2% female], 46 (31.7%) patients had cerebral infarction. Patients with cerebral infarction had higher rates of transient ischemic attack (TIA) (50.0% and 20.2%, χ2=13.37, P<0.001), cardiac valvular anomalies (32.6% and 11.1%, χ2=9.86, P=0.002), lupus anticoagulant (LA) (87.0% and 42.4%, χ2=25.35, P<0.001) and triple antiphospholipid antibodies (aPL) positivity (50.0% and 11.1%, χ2=26.64, P<0.001). The aGAPSS value was significantly higher in patients with cerebral infarction compared to those without [13(11, 14) and 9(7, 13), U=934.50, P<0.001]. The independent risk factors for PAPS-associated cerebral infarction were TIA [ OR (95% CI)= 3.612 (1.387, 9.403), P=0.009]、triple aPL positivity[ OR(95% CI)=8.904 (3.169, 25.019), P<0.001], higher aGAPSS[ OR(95% CI)=1.421(1.209, 1.670), P<0.001]. Conclusion:Patients with cerebral infarction may have a higher risk of thrombus recurrence. TIA, triple aPL positivity and higher aGAPSS are independent risk factors for PAPS patients with cerebral infarction.

Clinical characteristics of 37 antiphospholipid syndrome patients complicated by autoimmune hemolytic anemia / 中华内科杂志

Objective:We sought to investigate the clinical characteristics and risk factors of antiphospholipid syndrome (APS) complicated by autoimmune hemolytic anemia (AIHA).Methods:Retrospective anaysis.Three hundred fifteen consecutive patients with APS were enrolled at the Department of Rheumatology of Peking Union Medical College Hospital between May 2017 to May 2021, and their clinical manifestations[including initial symptoms, time interval between APS onset and diagnosis, systemic lupus erythematosus(SLE), thrombotic events, obstetric morbidity, and extra-criteria manifestations] and laboratory test results[including blood routine, antiphospholipid antibodies(aPLs), blood lipid profile, homocysteine, anti-nuclear antibody profile, immunoglobulin levels, and complement levels] were collected. Then, univariate and multivariate logistic regression analyses were performed. Clinical features and risk factors were analyzed using univariable and multivariable logistic regression analysis.Results:Among 315 APS patients, 37 cases (11.7%) were complicated by AIHA, and AIHA was the first manifestation or co-occurrence. The median time interval between APS onset and diagnosis was 12 months. The proportion of SLE in APS patients combined with AIHA was higher than that in APS patients without AIHA[62.2%(23/37) vs. 19.4%(54/278), P<0.001]. There was no significant difference in the proportions of thrombosis and pregnancy morbidity between the two groups. In terms of extra-criteria manifestations, APS patients with AIHA had a significantly ( P<0.05) greater risk of thrombocytopenia ( OR=6.19, 95% CI 2.81-13.65) and higher proportions of hypocomplementemia, a positive lupus anticoagulant (LA) result, double aPLs positivity[i.e., any two of the following antibodies were positive: LA, anticardilolipin antibody(aCL), and anti-β2 glycoprotein Ⅰ(β2GPⅠ)], and triple aPLs positivity (i.e., LA, aCL, and anti-β2GPⅠ antibodies were all positive). Multivariate logistic regression analysis showed that SLE ( OR=3.46,95% CI 1.60-7.48), thrombocytopenia ( OR=2.56,95% CI 1.15-5.67), and hypocomplementemia ( OR=4.29,95% CI 2.03-9.04) were independent risk factors for the complication of APS. In the primary APS subgroup, multivariate logistic regression analysis showed that livedo reticularis ( OR=10.51,95%CI 1.06-103.78), thrombocytopenia ( OR=3.77, 95% CI 1.23-11.57), and hypocomplementemia ( OR=5.92,95% CI 1.95-17.95) were independent risk factors for the complication of APS. Conclusions:AIHA is not rare in APS patients; moreover, it occurs more frequently in APS secondary to SLE and is more likely to present with a variety of extra-criteria manifestations. Patients with AIHA should be promptly tested for antiphospholipid antibody profiles and alerted to the possibility of thrombotic events.

Manifestaciones clínicas "no criterio" del Síndrome Antifosfolipídico. Presentación de una cohorte nacional

Introducción: El síndrome antifosfolipídico (SAF) es una afección de origen autoinmune caracterizada por trombosis, pérdidas fetales recurrentes y anticuerpos antifosfolipídicos (aFL). Existen manifestaciones clínicas no contempladas en los criterios clasificatorios, que se denominan manifestaciones no criterio. Objetivo: Analizar las manifestaciones clínicas del SAF, enfatizando las manifestaciones no criterio y su relación con el perfil de autoanticuerpos en un hospital general de Montevideo, Uruguay. Métodos: Se realizó un estudio retrospectivo de las historias clínicas de pacientes con diagnóstico definitivo o sospecha de SAF en un servicio de medicina ambulatoria de enfermedades autoinmunes, en el Hospital Maciel, asistidos entre el 2010 y 2019. Resultados: Se incluyeron 78 pacientes, con edad media de 50,3 ± 14,5 años, 69 (88,5%) correspondió a sexo femenino. Cuarenta y seis (59,0%) pacientes presentaron SAF secundario, de los cuales 28 (35,9%) asociaron LES. La trombosis venosa de miembros inferiores fue la manifestación más frecuente (51,3%). Dieciocho (24,0%) pacientes presentaron trombosis arteriales en forma de accidente cerebrovascular. Cincuenta y nueve (75.6%) casos presentaron, además de las manifestaciones clasificatorias, alguna de las manifestaciones "no criterio" y éstas se manifestaron de forma aislada en 10 (12.8%) pacientes. Las manifestaciones no clasificatorias más frecuentes fueron artralgias, livedo reticularis, migraña y trombocitopenia. Se observó una asociación significativa entre la presencia de anti-ß2GPI con manifestaciones cutáneas y de trombocitopenia con al menos una manifestación trombótica. Conclusiones: Las manifestaciones "no criterio" del SAF se presentaron en casi 3 de cada 4 casos, frecuencia similar a la observada en otras series. La presencia aislada de manifestaciones "no criterio" podrían hacer sospechar un SAF y en algunos casos, conducir a la solicitud de anticuerpos.

Introduction: Antiphospholipid syndrome (APS) is an autoimmune condition characterized by thrombosis, recurrent fetal loss, and antiphospholipid antibodies. There are clinical manifestations not contemplated in the classification criteria, which are called non-criterion manifestations. Objective: To analyze the clinical manifestations of APS, emphasizing the non-criterion manifestations and their relationship with the autoantibody profile in a general hospital in Montevideo, Uruguay. Methods: A retrospective analysis of the medical records of patients with a definitive or suspected diagnosis of APS in an outpatient medicine service for autoimmune diseases, at the Maciel Hospital, assisted between 2010 and 2019, was carried out. Results: 78 patients were included, with a mean age of 50.3 +/- 14.5 years, 69 (88.5%) were female. Forty-six (59.0%) patients presented secondary APS, of which 28 (35.9%) associated SLE. Venous thrombosis of the lower limbs was the most frequent manifestation (51.3%). Eighteen (24.0%) patients presented arterial thrombosis in the form of cerebrovascular accident. Fifty-nine (75.6%) cases presented, in addition to the classification manifestations, some of the "non-criterion" manifestations and these manifested in an isolated way in 10 (12.8%) patients. The most frequent non-classifying manifestations were arthralgia, livedo reticularis, migraine and thrombocytopenia. A significant association was observed between the presence of anti-ß2GPI with cutaneous manifestations and thrombocytopenia with at least one thrombotic manifestation. Conclusions: Non-criterion manifestations of APS occurred in almost 3 out of 4 cases, a frequency similar to that observed in other series. The isolated presence of "non-criterion" manifestations could lead to suspicion of APS and, in some cases, lead to the request for antibodies.

Introdução: A síndrome antifosfolipídica (SAF) é uma doença de origem auto-imune caracterizada por trombose, perdas fetais recorrentes e anticorpos antifosfolípidos (aFL). Existem manifestações clínicas não abrangidas pelos critérios de classificação, que são designadas por manifestações não-critério. Objetivo: Analisar as manifestações clínicas da SAF, enfatizando as manifestações não-critério e sua relação com o perfil de auto-anticorpos em um hospital geral de Montevidéu, Uruguai. Métodos: Foi realizado um estudo retrospectivo dos prontuários de pacientes com diagnóstico definitivo ou suspeita de SAF em um serviço ambulatorial de doenças autoimunes do Hospital Maciel, atendidos entre 2010 e 2019. Resultados: Foram incluídos 78 pacientes, com idade média de 50,3 +/- 14,5 anos, sendo 69 (88,5%) do sexo feminino. Quarenta e seis (59,0%) pacientes apresentavam PFS secundária, dos quais 28 (35,9%) tinham LES associado. A trombose venosa dos membros inferiores foi a manifestação mais frequente (51,3%). Dezoito (24,0%) doentes apresentaram trombose arterial sob a forma de acidente vascular cerebral. Cinquenta e nove (75,6%) casos apresentaram, para além das manifestações classificatórias, algumas das manifestações "não-critério" e estas manifestações foram isoladas em 10 (12,8%) doentes. As manifestações não classificatórias mais frequentes foram artralgias, livedo reticularis, enxaqueca e trombocitopenia. Foi observada uma associação significativa entre a presença de anti-ß2GPI com manifestações cutâneas e trombocitopenia com pelo menos uma manifestação trombótica. Conclusões: As manifestações "não-critério" de SAF ocorreram em quase 3 de cada 4 casos, frequência semelhante à observada noutras séries. A presença isolada de manifestações "não-critério" pode levantar a suspeita de SAF e, nalguns casos, levar à pesquisa de anticorpos.