A case of high level of elevated antiphospholipid antibodies positive secondary to infective endocarditis / 中国综合临床

It is quiet rare that transient high level of elevated antiphospholipid (aLP) antibodies are triggered by infective endocarditis(IE). We report a young woman who went to hospital because of fever was diagnosed with IE, she was suffering from lower and upper arterial thrombosis, tests showed that anticardiolipin and anti-beta2-glycoprotein(GP)-1 IgM antibodies elevated highly. She had mitral valve replacement surgery, echocardiography detected vegetation on mitral valve, multiple blood culture showed negative, after treatment of antibiotics,the second cardiac surgery and warfarin, the patient got stable condition and the upper limb arterial thrombosis disappeared. Three months later, aLP antibodies tests came back negative. This case illustrate that IE could lead to transient high level of elevated aLP antibodies, does that increase the risk of thrombosis of IE patient is unknown, what if we find that phenomenon earlier and prescribe anticoagulant drugs, that need more observation.

Osteoporosis and osteonecrosis in systemic lupus erythematosus / Osteoporosis y osteonecrosis en el lupus eritematoso sistémico

ABSTRACT Half of the patients with systemic lupus erythematosus (SLE) will have a reduced bone density and more than one in ten will develop osteoporosis (OP) prematurely. Multiple risk factors have been related to loss of bone mass, but just a few are modifiable, such as adequate vitamin D and calcium intakes, weight bearing exercise, controlling SLE activity and limiting the use of glucocorticoids (GC). GC have also been strongly associated to osteonecrosis or avascular necrosis (AVN). The main consequences of OP and AVN are fractures, which lead to significant functional limitation, loss of quality of life and increased morbidity. OP-related fractures can be reduced by performing appropriate screening with bone densitometries and providing prophylactic treatment when long-term or high dose GC are needed. No formal screening is available for AVN; but diagnosis is made by imaging (X-ray, bone scan or advanced imaging where appropriate). Aiming for the lowest dose possible of GC in combination with immunosuppression as well as an early recognition of the symptoms will prevent further complications. This manuscript is a practical review of the epidemiology, pathophysiology, and management of OP and AVN in patients with SLE, based on the available evidence and guidelines.

RESUMEN La mitad de los pacientes con lupus eritematoso sistémico (LES) tendrá una densidad ósea disminuida, y más de uno de cada 10 desarrollará osteoporosis (OP) prematuramente. Son múltiples los factores de riesgo que se han relacionado con la pérdida de la masa ósea, pero solo unos pocos son modificables, tales como la ingesta de niveles adecuados de vitamina D y de calcio, ejercicio con pesas, controlar la actividad del LES, y limitar el uso de glucocorticoides (GC). También se ha encontrado una estrecha relación entre el uso de GC y osteonecrosis o a necrosis avascular (NAV). Las principales consecuencias de la OP y de la NAV son fracturas, que generan una limitación funcional importante, pérdida de la calidad de vida y aumento de la morbilidad. Las fracturas por osteoporosis se pueden reducir mediante un tamizaje adecuado con densitometría ósea y administrando tratamiento profiláctico cuando se requieren GC de largo plazo o a altas dosis. No existe un tamizaje formal para la NAV, pero su diagnóstico se realiza con imágenes (radiografía, gammagrafía ósea o imágenes avanzadas cuando corresponda). El apuntar a la menor dosis posible de GC, en combinación con inmunosupresión, además de la temprana identificación de los síntomas, ayudará a prevenir otras complicaciones. El presente artículo es una revisión práctica de la epidemiología, la fisiopatología y el manejo de la OP y la NAV en pacientes con LES, en función de la evidencia y de las guías disponibles.

Catastrophic antiphospholipid syndrome / Síndrome antifosfolípido catastrófico

ABSTRACT The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by the development of thrombotic events and/or obstetric morbidity in the presence of antiphospholipid antibodies (aPL), such as the lupus anticoagulant (LA), anticardiolipin antibodies (aCL) or anti- β 2-glycoprotein I antibodies (a β2 GPI). In 1992, Ronald A. Asherson described a very aggressive clinical variant of this syndrome characterized by the development of multiple thrombotic manifestations, simultaneously or in a short period of time. The term catastrophic APS was proposed and since then it is known by this name.

RESUMEN El síndrome antifosfolípido (SAF) es una enfermedad sistêmica autoinmune, caracterizada por el desarrollo de eventos trombóticos y/o morbilidad obstétrica en presencia de anticuerpos antifosfolípidos (aPL), tales como el anticoagulante lúpico (AL), los anticuerpos anticardiolipina (aCL) o anticuerpos anti- β2-glicoproteína I (aβ2GPI). En 1992, Ronald A. Asherson describió una variante clínica muy agresiva de este síndrome, caracterizada por el desarrollo de múltiples manifestaciones trombóticas, de manera simultánea o dentro de un corto periodo de tiempo. Se propuso entonces el término SAF catastrófico y desde entonces se le ha conocido por ese nombre.

Síndrome antifosfolipídico obstétrico / Obstetric antiphospholipid syndrome / Síndrome antifosfolípide obstétrica

Resumen: El síndrome antifosfolipídico obstétrico puede ser causa de importante morbilidad materno-fetal. Los criterios diagnósticos se definen en 1999 (criterios de Sapporo) que son revisados en 2006 (Sydney), basados en criterios clínicos y de laboratorio. En el 2006 la sociedad internacional de hemostasis y trombosis propone los criterios que definen las morbilidades del embarazo vinculadas al mismo (pérdida fetal tardía, pérdida recurrente del embarazo, parto pretérmino, enfermedad tromboembólica). El objetivo terapéutico es prevenir complicaciones materno-fetal (trombosis maternas y prevenir complicaciones obstétricas). El tratamiento siempre debe ser individualizado según cada caso particular. Se realiza una revisión sobre las distintas situaciones posibles, finalizando con recomendaciones para el mismo.

Abstract: Obstetric antiphospholipid syndrome can be the cause of significant maternal-fetal morbidity. Diagnostic criteria are defined in 1999 (Sapporo criteria) which are revised in 2006 (Sydney), based on clinical and laboratory criteria. In 2006, the International Society of Haemostasis and Thrombosis proposed the criteria that define the morbidities of pregnancy related to it (late fetal loss, recurrent pregnancy loss, preterm delivery, thromboembolic disease). The therapeutic objective is to prevent maternal-fetal complications (maternal thrombosis and prevent obstetric complications). Treatment must always be individualized according to each particular case. A review is carried out on the different possible situations, ending with recommendations for the same.

Resumo: A síndrome antifosfolipídica obstétrica pode ser a causa de morbidade materno-fetal significativa. Os critérios diagnósticos são definidos em 1999 (critérios de Sapporo) que são revisados em 2006 (Sydney), com base em critérios clínicos e laboratoriais. Em 2006, a Sociedade Internacional de Hemostasia e Trombose propôs os critérios que definem as morbidades da gravidez a ela relacionadas (perda fetal tardia, perda recorrente da gravidez, parto prematuro, doença tromboembólica). O objetivo terapêutico é prevenir complicações materno-fetais (trombose materna e prevenir complicações obstétricas). O tratamento deve ser sempre individualizado de acordo com cada caso particular. É feita uma revisão sobre as diferentes situações possíveis, terminando com recomendações para o mesmo.

Resultados obstétricos en gestantes diagnosticadas de síndrome antifosfolípido / Obstetric outcomes in pregnant women diagnosed of antiphospholipid syndrome

INTRODUCCIÓN: El síndrome antifosfolípido (SAF) es una enfermedad autoinmune caracterizada por la aparición de trombosis, complicaciones obstétricas y la presencia de anticuerpos antifosfolípidos. El objetivo de este estudio fue evaluar los resultados obstétricos en gestantes diagnosticadas de síndrome antifosfolípido, así como evaluar las condiciones que podrían influir en estos resultados. MATERIAL Y MÉTODOS: Se realizó un estudio retrospectivo de gestantes con diagnóstico previo de SAF, que fueron atendidas en nuestro centro entre los años 2007 y 2017. RESULTADOS: En el período de estudio se recogieron 35 gestantes con SAF, con un total de 50 gestaciones. Se empleó heparina en el 100% de las gestaciones y ácido acetilsalicílico en el 96%. La aparición de alguna complicación obstétrica ocurrió en el 34% de las gestaciones estudiadas. El perfil de anticuerpos triple positivo se asoció a mayor porcentaje de partos prematuros. La presencia de anticoagulante lúpico de forma aislada no se asoció a peores resultados obstétricos. DISCUSIÓN: La gestación en la mujer con SAF supone un importante reto, que precisa de un manejo multidisciplinar por parte del obstetra y el reumatólogo. Por otro lado, el perfil de anticuerpos antifosfolípidos podría detectar a las pacientes con mayor riesgo con el fin de adecuar el tratamiento y mejorar los resultados obstétricos.

INTRODUCTION: The antiphospholipid syndrome (APS) is an autoinmune disease characterized by the occurence of thrombosis, obstetric morbidity and the presence of antiphospholipid antibodies. The aim of this study was to evaluate the obstetric outcomes in pregnant women diagnosed of antiphospholipid syndrome, as well as examine the conditions which may influence in those results. MATERIALS AND METHODS: A retrospective study was undertaken with pregnant women diagnosed of APS, who were attended in our hospital between 2007 and 2017. RESULTS: During the period of study 35 patients with APS and a sum of 50 pregnancies were gathered. Heparin was used in all pregnancies and acetylsalicylic acid in 96%. Any adverse obstetric outcome occurred in 34% of the pregnancies in the study. The triple positivity of antiphospholipid antibodies was associated to higher percentage of premature deliveries. The lupus anticoagulant alone was not related to worse obstetric outcomes. CONCLUSIONS: Pregnancy in APS patients means a challenge, requiring a multidisciplinary management by Obstetricians and Rheumathologists. On the other hand, the antiphospholipid antibodies profile could help to recognize those patients at risk, in order to adequate treatment and improve obstetric results.

Prevalence and clinical significance of antiphospholipid antibodies among hospitalized COVID-19 patients

Objective: To describe the prevalence of antiphospholipid antibodies in coronavirus disease-19 (COVID-19) and to find potential associations between antiphospholipid antibody positivity and clinical outcomes. Methods: From September to November 2020, clinical and laboratory data were collected from 50 COVID-19 patients hospitalized at Saiful Anwar General Hospital in Malang, Indonesia. Antiphospholipid antibodies were measured by finding IgM anti-β2 glycoprotein, lupus anticoagulant, and IgM/IgG anticardiolipin. Clinical characteristics, thrombotic events, ICU admission, and mortality during hospitalization were recorded. Disease severity was defined by the Guidelines for the Prevention and Control of COVID-19, Indonesia. Results: Among 50 patients, 5 patients (10.0%) were positive for antiphospholipid antibodies: 4 patients (80.0%) had IgM anti-β2 glycoprotein and 1 patient had IgG anti-cardiolipin (20.0%) and IgM anti-cardiolipin (20.0%), none of lupus anticoagulant was detected. Antiphospholipid antibodies were associated with anosmia (OR 8.1; 95% CI 1.1-57.9; P=0.018), nausea and vomiting (OR 12.4; 95% CI 1.2-122.6; P=0.010), diarrhea (OR 9.8; 95% CI 1.3-70.9; P=0.010), cardiovascular disease (OR 1.4; 95% CI 1.0-1.9; P=0.001), chronic kidney disease (OR 12.0; 95% CI 1.6-90.1; P=0.05), acute coronary syndrome (OR 29.3; 95% CI 2.0-423.7; P=0.001), moderate (OR 0.11; 95% CI 0.01-1.10; P=0.031) and severe (OR 18.5; 95% CI 1.8-188.4; P=0.002) disease severity, and in-hospital mortality (OR 8.1; 95% CI 1.1-57.9; P=0.018). However, there is no correlation between the presence of antiphospholipid antibody and ICU admission. Conclusions: In summary, the prevalence of antiphospholipid antibodies in COVID-19 patients is low, mainly against IgM anticardiolipin, and is associated with an acute coronary syndrome, gastrointestinal manifestations, moderate and severe disease severity, and increased risk of mortality.

Clinical and laboratory characteristics of Brazilian versus non-Brazilian primary antiphospholipid syndrome patients in AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) clinical database and repository

Abstract Background: Antiphospholipid syndrome (APS) is characterized by episodes of thrombosis, obstetric morbidity or both, associated with persistently positive antiphospholipid antibodies (aPL). Studying the profile of a rare disease in an admixed population is important as it can provide new insights for understanding an autoimmune disease. In this sense of miscegenation, Brazil is characterized by one of the most heterogeneous populations in the world, which is the result of five centuries of interethnic crosses of people from three continents. The objective of this study was to compare the clinical and laboratory characteristics of Brazilian vs. non-Brazilian primary antiphospholipid syndrome (PAPS) patients. Methods: We classified PAPS patients into 2 groups: Brazilian PAPS patients (BPAPS) and PAPS patients from other countries (non-BPAPS). They were compared regarding demographic characteristics, criteria and non-criteria APS manifestations, antiphospholipid antibody (aPL) profile, and the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). Results: We included 415 PAPS patients (88 [21%] BPAPS and 327 [79%] non-BPAPS). Brazilian patients were significantly younger, more frequently female, sedentary, obese, non-white, and had a higher frequency of livedo (25% vs. 10%, p < 0.001), cognitive dysfunction (21% vs. 8%, p = 0.001) and seizures (16% vs. 7%, p = 0.007), and a lower frequency of thrombocytopenia (9% vs. 18%, p = 0.037). Additionally, they were more frequently positive for lupus anticoagulant (87.5% vs. 74.6%, p = 0.01), and less frequently positive to anticardiolipin (46.6% vs. 73.7%, p < 0.001) and anti-ß2-glycoprotein-I (13.6% vs. 62.7%, p < 0.001) antibodies. Triple aPL positivity was also less frequent (8% vs. 41.6%, p < 0.001) in Brazilian patients. Median aGAPSS was lower in the Brazilian group (8 vs. 10, p < 0.0001). In the multivariate analysis, BPAPS patients still presented more frequently with livedo, cognitive dysfunction and sedentary lifestyle, and less frequently with thrombocytopenia and triple positivity to aPL. They were also less often white. Conclusions: Our study suggests a specific profile of PAPS in Brazil with higher frequency of selected non-criteria manifestations and lupus anticoagulant positivity. Lupus anticoagulant (not triple positivity) was the major aPL predictor of a classification criteria event.

Anorectal diseases in patients with Antiphospholipid syndrome: a cross-sectional study

Abstract Background: Hemorrhoid disease (HD) is one of the most common gastrointestinal complaints worldwide, affecting 4.4% of the general population in the United States. Since antiphospholipid syndrome (APS) may lead to intra-abdominal thrombosis, one may expect that this condition can impact the risk for HD development. Additionally, as APS patients are more prone to thrombosis and treatment with anticoagulants may increase risk of bleeding, one may also infer that rates of HD complications may be higher in this scenario. Nevertheless, no data in these regards have been published until now. The objective of the present study is to evaluate frequency of HD and describe its complications rates in antiphospholipid syndrome APS patients. Methods: We consecutively invited patients who fulfilled APS criteria to undergo proctological examination. After examination, patients were divided in two groups, based on the presence of HD, and compared regarding different clinical manifestations and antiphospholipid profile. We performed the analysis of the data, using chi-square and Mann Whitney U when applicable and considering a significance level of 0.05. Multivariate regression analysis included age and variables with p < 0.10 in the bivariate analysis. Results: Forty-one APS patients agreed to undergo proctological examination. All were female and overall median age was 43 (36-49). Seventeen (41.4%) patients were diagnosed with HD, with the following frequency distribution: 7 internal (41.2%), 4 external (23.5%) and 5 mixed hemorrhoids (29.4%). Of the internal hemorrhoids, 5 patients were classified as grade I (71.4%), 1 grade II (14.3%), and 1 grade IV (14.3%). Prior gestation ( p = 0.067) and constipation ( p = 0.067) correlated with a higher frequency of HD. In multivariate analysis, constipation remained as an important risk factor (OR 3.92,CI95% 1.03-14.2, p = 0.037). Five out of 17 patients (29.4%) reported anal bleeding, but it did not correlate with warfarin dose ( p = 0.949). Surgical treatment was indicated for 10 patients (58.8%). Other anorectal findings were anal fissure, plicoma, condyloma and one chlamydial retitis. Conclusion: We found an unexpected high frequency of hemorrhoids in APS patients, with a great proportion requiring surgical treatment.(AU)

Brachial Artery Thrombosis in an 8-year-old Boy with Antiphospholipid Antibodies Induced by Mycoplasma pneumoniae Infection: a Case Report

Antiphospholipid antibodies may be produced in cases involving autoimmune diseases and can sometimes be caused by infections, such as Mycoplasma pneumoniae infection. However, antiphospholipid antibodies causing thrombosis associated with M. pneumoniae pneumonia in children have rarely been reported. We report a case of an 8-year-old boy with M. pneumoniae pneumonia with antiphospholipid antibodies, complicated by brachial artery thrombosis. He was found to have antiphospholipid antibodies and low protein S levels. The brachial artery thrombus was removed via thrombectomy. The titers of antiphospholipid antibodies turned normal within 5 months. This is a rare case of M. pneumoniae infection with brachial artery thrombosis associated with transient antiphospholipid antibodies.

Study on the expression of antiphospholipid antibody subtypes in primary glomerulopathy / 中国实用内科杂志

OBJECTIVE: To discuss expression of antiphospholipid antibody subtypes in primary glomerular diseases. METHODS: All1021 cases who were admitted to our center between June 2015 and July 2017 in Kidney Disease Center, First Affiliated Hospital,College of Medicine, Zhejiang Universityhad renal biopsy in our center and they were praved to have primary glomerular diseases(303 cases of membranous nephropathy, 483 cases of IgA nephropathy, 76 cases of mesangial proliferative glomerulonephritis, 119 cases of minimal change nephropathy and 40 cases of focal segmental glomerulosclerosis). The levels of anti-cardiolipin(ACL) antibody subtypes(IgG, IgM and IgA)and anti-β2 glycoprotein 1(β2 GP1) antibody subtypes(IgG, IgM and IgA) were measured and compared.RESULTS: The positive rate of APA in membranous nephropathy group was highest(17.5%) and in minimal change nephropathy was lowest group(11.8%), but there were no significant differences among the groups. The positive rates of ACL in IgA nephropathy and mesangial proliferative glomerulonephritis were 11.4% and 14.5% respectively, which were significantly higher than those of anti-β2 GP1 antibody(P< 0.001, P = 0.009 respectively). The positive rate of anti-β2 GP1 antibody in membranous nephropathy group was 11.2%,significantly higher than that in the other four groups. The positive rate of ACL-IgM in mesangial proliferative glomerulonephritis group was 13.2%, which was significantly higher than that in the other four groups(P< 0.05). The positive rate of ACL-IgA in IgA nephropathy group was 5.8%, which was significantly higher than the other four groups, and there was no statistical difference(P<0.05).CONCLUSION: Antiphospholipid antibody is positive in patients with primary glomerular diseases, and the positive rate of its subtypes varies among the different pathological types of glomerulonephritis, which can be helpful to differential diagnosis and treatment of the disease.

Actualización diagnóstico-terapéutica del síndrome antifosfolípido o de Hughes / Therapeutic diagnostic update of Hughes antiphospholipid syndrome

El síndrome antifosfolipídico es una enfermedad del sistema inmune (trombofilia), que se caracteriza por la asociación de los anticuerpos antifosfolipídicos con trombosis de repetición, abortos o pérdidas fetales recurrentes y trombocitopenia. Descrito inicialmente en el lupus eritematoso sistémico, aparece también en personas que no reúnen criterios de alguna enfermedad conocida, por lo que su identificación y tratamiento adquieren gran importancia en personas con fenómenos trombóticos aparentemente inexplicables y en mujeres con abortos y muertes fetales recurrentes sin otra causa reconocible. A pesar de que los fenómenos clínicos que caracterizan a esta enfermedad ocurren frecuentemente, la incidencia es baja. Por lo que toma importancia, la identificación de los anticuerpos antifosfolípidos mediante ensayos para su detección. El síndrome antifosfolípido no tiene cura, pero pueden prevenirse los eventos trombóticos corrigiendo los factores de riesgo para trombosis y usando una terapia con anticoagulante oral para el resto de la vida.

Antiphospholipid Syndrome is a disease of the immune system (thrombophilia), which is characterized by the association of antiphospholipid antibodies with recurrent thrombosis, abortions or recurrent fetal losses and thrombocytopenia. Initially described in systemic lupus erythematosus, it also appears in people who do not meet the criteria of a known disease, so its identification and treatment acquire great importance in people with apparently inexplicable thrombotic phenomena and in women with abortions and recurrent fetal deaths without other cause recognizable. Although the clinical phenomena that characterize this disease occur frequently, the incidence is low. So it is important, the identification of antiphospholipid antibodies through tests for their detection. Antiphospholipid Syndrome has no cure, but thrombotic events can be prevented by correcting the risk factors for thrombosis and using an oral anticoagulant therapy for the rest of your life.

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.

The association between systemic lupus erythematosus and dementia: a meta-analysis / Associação entre lúpus eritematoso sistêmico e demência: um metanálise

Abstract A growing body of evidence indicates that systemic lupus erythematosus (SLE) is associated with increased risk of cognitive impairment and dementia. However, to date, no studies have been conducted to quantitatively summarize and evaluate the consistency of data. Objective: To quantitatively evaluate the relationship of SLE and antiphospholipid antibodies (aPL) with cognitive dysfunction and dementia. Methods: All relevant literature was retrieved from Pubmed, Scopus, and PsycINFO databases. The meta-analysis was performed using effect estimates and 95% confidence intervals (CIs) to calculate pooled risk estimates. The heterogeneity among studies was also examined. Results: The meta-analysis included 11 original studies involving a total of 81,668 patients with dementia and 407 patients with cognitive dysfunction. There were significant associations on fixed-effect models between SLE and dementia (3 studies; RR=1.50; 95% CI=1.37-1.64), SLE and cognitive dysfunction (4 studies; OR=2.97; 95% CI=1.72-5.15), and aPL and cognitive dysfunction (5 studies, OR=1.97; 95% CI=1.55-2.52). We also combined cognitive dysfunction and dementia outcomes as they both represented cognitive impairment. There were significant associations between aPL and cognitive impairment (6 studies; OR=2.03; 95% CI=1.62-2.55), and SLE and cognitive impairment (7 studies; OR=1.83; 95% CI=1.42-2.35). Moderate heterogeneity (I2=45.7%) was found in the association between SLE and cognitive impairment, low heterogeneity (I2=21.8%) in the association between SLE and dementia, and near zero heterogeneity for the other three main analyses. Conclusion: Both SLE and aPL are associated with cognitive impairment.

Resumo Um volume crescente de evidências indica que o lúpus eritematoso sistêmico (LES) está associado ao aumento do risco de comprometimento cognitivo e demência. No entanto, até o presente momento nenhum estudo foi conduzido a fim de resumir e avaliar quantitativamente a consistência dos dados. Objetivo: Avaliar quantitativamente a relação entre o LES e anticorpos anticorpos antifosfolípides (aPL) com disfunção cognitiva e demência. Métodos: Toda literatura relevante foi recuperada das bases de dados Pubmed, Scopus e PsycINFO. A meta-análise foi realizada utilizando as estimativas de efeito e os intervalos de confiança de 95% (ICs) para calcular as estimativas de risco combinadas. A heterogeneidade entre os estudos também foi examinada. Resultados: A meta-análise incluiu 11 estudos originais com um total de 81.668 pacientes com demência e 407 pacientes com disfunção cognitiva. Houve associações significativas (modelos de efeitos fixos) entre LES e demência (3 estudos, RR=1,50; IC 95%=1,37-1,64), LES e disfunção cognitiva (4 estudos; OR=2,97; IC 95%=1,72-5,15), e aPL e disfunção cognitiva (5 estudos, OR=1,97; IC 95%=1,55-2,52). Além disso, combinamos os resultados da disfunção cognitiva e demência, uma vez que ambos representaram déficit cognitivo. Houve associações significativas entre aPL e comprometimento cognitivo (6 estudos, OR=2,03, IC 95%=1,62-2,55), e LES e comprometimento cognitivo (7 estudos, OR=1,83; IC 95%=1,42-2,35). Uma heterogeneidade moderada (I2=45,7%) foi encontrada na associação entre LES e comprometimento cognitivo, heterogeneidade baixa (I2=21,8%) na associação entre LES e demência e heterogeneidade quase zero para as outras três principais análises. Conclusão: Tanto o LES como aPL estão associados a déficit cognitivo.

Antiphospholipid Syndrome Complicating Pneumococcal Meningitis

Background: Antiphospholipid syndrome is a multisystem auto-immune disordercharacterized by arterial or venous thrombosis in children. Case characteristics: 11-year-old child with pneumococcal meningitis also had cerebral sinus vein thrombosis andpulmonary artery segmental thrombosis. Observation: Pro-thrombotic evaluation showedpositive lupus anticoagulant at baseline and after 12 weeks. Investigations for lupus werenegative at admission and after one year of follow-up. Message: Antiphospholipidsyndrome is a possibility even in thrombosis occurring in the setting of meningitis

Anti-phospholipid syndrome in seven leprosy patients with thrombotic events on corticosteroid and/or thalidomide regimen: insights on genetic and laboratory profiles

Abstract INTRODUCTION Corticosteroids and/or thalidomides have been associated with thromboembolism events (TBE) in multibacillary (MB) leprosy. This report aimed to determine genetic and laboratory profiles associated with leprosy and TBE. METHODS Antiphospholipid antibodies (aPL), coagulation-related exams, prothrombin and Leiden's factor V mutations, and ß2-glycoprotein-I (ß2GPI) Val247Leu polymorphism were assessed. RESULTS Six out of seven patients with leprosy were treated with prednisone and/or thalidomide during TBE and presented at least one positive aPL. All patients presented ß2GPI polymorphism, and one showed prothrombin mutation. CONCLUSIONS Corticosteroid or thalidomide adverse effects and aPL and ß2GPI polymorphisms may cause TBE in patients with MB leprosy.

Neuritis óptica en presencia de anticuerpos antifosfolipidos de origen sifilítico: un diagnostico olvidado / Optic neuritis in the presence of antiphospholipid antibodies of syphilitic origin: a forgotten diagnosis

Resumen: la neuritis óptica es infrecuente como manifestación de sífilis ocular, la falta de características típicas genera retraso en el diagnóstico. Describimos el caso de una mujer de 47 años , inmunocompetente con historia de 4 meses de disminución progresiva de la agudeza visual de predominio izquierdo, asociado a dolor, inyección conjuntival y cefalea, al examen físico con visión de bultos y al fondo de ojo con signos de inflamación ocular dentro de la evaluación diagnostica presenta: VDRL y FTA-ABS positivo en suero, positividad de ANAS y anticuerpos anticardiolipinas igG, LCR con VDRL reactivo, se diagnostica neuritis óptica por neurosifilis en presencia de anticuerpos antifosfolipidos, iniciando tratamiento con penicilina cristalina 24 000 000 de unidades día por 14 días. En pacientes con signos de inflamación ocular debe realizarse VDRL, confirmarse con prueba treponemica, y realizar punción lumbar, el tratamiento precoz se asocia a mejora de desenlaces visuales.

Abstract :optic neuritis is uncommon as an ocular syphilis clinical presentation; the lack of typical features generates delay in the diagnosis. We describe the case of a 47-year-old woman, immunocompetent with a 4-month history of left visual acuity progressive of left side reduction, associated with pain, conjunctival injection and headache, physical examination with lumpy vision and fundus with signs of ocular inflammation, within the diagnostic evaluation, serum VDRL, FTA-ABS was reactive, with ANAS and IgG anticardiolipin antibodies serum positivity, lumbar punction was taken with reactive VDRL, optic neuritis by neurosyphilis was diagnosed, with antiphospholipid antibodies cross reactivity , treatment with crystalline penicillin 24 000 000 of units day for 14 days was started . In patients with signs of ocular inflammation, VDRL should be performed, confirmed with a treponemal test, and a lumbar puncture should be performed. Early treatment is associated with improvement of visual outcomes.

Prevalencia de anticuerpos antifosfolípidos y anti anexina V en pacientes dializados de Bahía Blanca / Prevalence of antiphospholipid antibodies and anti anexin V in dialysis patients in Bahía Blanca / Prevalência de anticorpos antifosfolípides e anti anexina V em pacientes em diálise em Bahía Blanca

En los pacientes hemodializados son frecuentes las oclusiones de los accesos vasculares por una diálisis insuficiente y en un bajo porcentaje por un estado hipercoagulable desencadenado por anticuerpos dirigidos contra determinados componentes fosfolipídicos. El objetivo del trabajo fue evaluar la prevalencia de estos autoanticuerpos (APL) y del marcador anti anexina V en 79 pacientes en plan de hemodiálisis y en 66 donantes de sangre de la ciudad de Bahía Blanca. Para la detección del anticoagulante lúpico (AL) se realizaron estudios coagulométricos básicos, pruebas de detección, corrección con mezclas con plasma normal y ensayos confirmatorios con lisados plaquetarios. En paralelo, se efectuaron ensayos inmunológicos séricos: anticuerpos anticardiolipinas (ACL) IgM/IgG, anticuerpos anti β2 Glicoproteina I (aβ2GPI) IgM/IgG y anticuerpos anti anexina V IgM/IgG. Para estimar las diferencias se realizó el test de Fisher con una significancia del 5%. No se detectó anticoagulante AL en ninguna de las dos poblaciones. La prevalencia de los ACL IgG fue mayor en los dializados que en los dadores (31,6% vs. 12,1%, p: 0,0056); la correspondiente a las antiβ2 GPI fue similar (2,5% en dializados vs. 7,6% en dadores, p: 0,2458), mientras que la correspondiente a la anti anexina V IgG resultó mayor en dializados (16,4% vs. 4,5%, p: 0,0316). Los resultados obtenidos sugieren la importancia de monitorear la presencia de anticuerpos antifosfolípidos y anti anexina V previo al ingreso de un plan de diálisis para prevenir eventos trombóticos.

In hemodialysis patients, occlusions of vascular access are frequent due to insufficient dialysis and in a low percentage, due to a hypercoagulable state triggered by antibodies directed against certain phospholipid components. The objective of this work was to evaluate the prevalence of these autoantibodies (APL) and the anti-annexin V marker in 79 patients undergoing hemodialysis and in 66 blood donors in the city of Bahía Blanca. For the detection of lupus anticoagulant (LA), basic coagulometric studies, detection tests, correction with mixtures with normal plasma and confirmatory tests with platelet lysates were performed. In parallel, serum immunological assays were performed: IgM/IgG anticardiolipin antibodies (ACL), IgM/IgG anti-β2 glycoprotein I (aβ2GPI) antibodies and IgM/IgG anti-annexin V antibodies. To estimate the differences, a Fisher test with a significance of 5% was performed. Lupus anticoagulant (LA) was not detected in any of the two populations. The prevalence of IgG ACL was higher in the dialysate than in the donors (31.6% vs. 12.1%, p: 0.0056); the corresponding antiβ2GPI was similar (2.5% dialysate vs. 7.6% donors, p: 0.2458), while the corresponding anti-Annexin V IgG was higher in dialysate (16.4% vs. 4.5%, p: 0.0316). The results obtained suggest the importance of monitoring the presence of antiphospholipid and anti-annexin V antibodies prior to entry to a dialysis plan to prevent thrombotic events.

Em pacientes hemodialisados são frequentes as oclusões dos acessos vasculares devido a uma diálise insuficiente e, um percentual baixo, a um estado de hipercoagulabilidade desencadeado por anticorpos dirigidos contra determinados componentes dos fosfolípidos. O objetivo do trabalho foi avaliar a prevalência desses autoanticorpos (APL) e do marcador anti Anexina V em 79 pacientes em plano de hemodiálise e em 66 doadores de sangue da cidade de Bahía Blanca. Para a detecção do anticoagulante lúpico (AL) foram realizados estudos coagulométricos básicos, testes de detecção, correção com misturas com plasma normal e ensaios de confirmação com lisados de plaquetas. Em paralelo se realizaram ensaios imunológicos séricos: anticorpos anticardiolipinas (ACL) a IgM/IgG, anticorpos anti β 2 GlicoproteinaI (aβ 2GPI) IgM/IgG e anticorpos anti Anexina V IgM/IgG. Para estimar as diferenças foi realizado o teste de Fisher com uma significância de 5%. Não foi detectado anticoagulante AL em qualquer uma das duas populações. A prevalência de ACL IgG foi maior nos dialisados que nos doadores (31,6% vs. 12,1%, p: 0,0056); a correspondente às anti β 2GPI foi semelhante (2,5% em dialisados vs. 7,6% em doadores, p: 0,2458), enquanto que o correspondente à anti Anexina V IgG foi maior em dialisados (16,4% vs. 4.5 %, p: 0,0316). Os resultados obtidos sugerem a importância de monitorar a presença de anticorpos antifosfolipídios e anti Anexina V antes de entrar em um plano de diálise para prevenção de eventos trombóticos.

Síndrome antifosfolípido catastrófico / Catastrophic antiphospholipid syndrome

El síndrome antifosfolípido está definido por la combinación de manifestaciones clínicas trombóticas y/u obstétricas y un título persistentemente alto y significativo de anticuerpos antifosfolípidos. La presencia de múltiples trombos en lechos vasculares pequeños que lleva a falla multiorgánica, simultáneamente o en menos de 1 semana, define al síndrome antifosfolípido catastrófico el cual conlleva alta mortalidad; sin embargo, la sospecha diagnóstica y la institución temprana del tratamiento, definitivamente inciden en el pronóstico de éstos pacientes(AU)

Antiphospholipid syndrome is defined by the combination of thrombotic and/or obstetric clinical manifestations and a persistently high and significant title of antiphospholipid antibodies. The presence of multiple thrombi in small vascular beds leading to multi-organ failure that occurs simultaneously or in less than 1 week, and defines the catastrophic antiphospholipid syndrome which carries high mortality, The suspected diagnosis and early treatment affects the prognosis of these patients(AU)

A 15-year single centre retrospective study of antiphospholipid syndrome patients from Northern Malaysia

Background: Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPLs) based on the Sydney criteria. We aimed to explore the clinico-laboratory features and treatment strategies of APS patients retrospectively. Methodology: The medical records of APS patients registered under Hospital Universiti Sains Malaysia (Kelantan state) between 2000 and 2015 were reviewed. Results: A total of 17 APS subjects (age 40.7 ± 12.8 years) including 11 primary (64.7%) and six secondary APS (35.3%) patients were identified. The follow-up period was 9.5 ± 6.7 years with male:female ratio of 1.0:4.7. Pregnancy morbidity was the most common clinical manifestation (11/14; 78.6%) followed by recurrent venous thrombosis (10/17; 58.8%). For other clinical features, menorrhagia was the most frequently observed manifestation (4/14; 28.6%) followed by aPLs-associated thrombocytopenia (4/17; 23.5%) and ovarian cyst (3/14; 21.4%). LA and aCL were positive in 94.1% (16/17) and 81.8% (9/11) of the patients, respectively. APTT value (76.7 ± 17.0 sec) was significantly high (p < 0.05). Low intensity warfarin alone was successful to maintain target INR (2.0 - 3.0) and prevent recurrence of thrombosis. Conclusion: The tendency of pregnancy morbidity in this cohort of Malaysian Kelantanese APS patients was high compared to other previously reported APS cohorts. Low intensity warfarin was successful in preventing recurrence of thrombosis, however, APS women receiving long-term anticoagulants should be monitored for possible occurrence of menorrhagia and ovarian cysts.

Recurrent Ventricular Tachycardia and Peripheral Gangrene in a Young Child.

A 10-year-old girl presented with sudden onset recurrent ventricular tachycardia and symmetrical distal peripheral gangrene. She also had pulmonary thromboembolism and cerebral sinus venous thrombosis. Investigations revealed anemia, hemolysis, hypocomplementemia, and elevated IgM anti-beta2 glycoprotein antibody levels. Electrocardiogram and echocardiogram suggested features of a rare cardiac anomaly, which was confirmed at autopsy.