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.

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.

Epidemiological, clinical and immune factors that influence the persistence of antiphospholipid antibodies in leprosy

Abstract Introduction: Antiphospholipid antibodies (aPL) are described in individuals with leprosy without the clinical features of antiphospholipid antibody syndrome (APS), a condition involving thromboembolic phenomena. We have described the persistence of these antibodies for over 5 years in patients with leprosy after specific treatment. Objectives: To determine whether epidemiological, clinical and immunological factors played a role in the longterm persistence of aPL antibodies in leprosy patients after multidrug therapy (MDT) had finished. Methods: The study sample consisted of 38 patients with a diagnosis of leprosy being followed up at the Dermatology and Venereology Outpatient Department at the Alfredo da Matta Foundation (FUAM) in Manaus, AM. ELISA was used to detect anticardiolipin (aCL) and anti-β2 glycoprotein I (anti-β2GPI) antibodies. Patients were reassessed on average of 5 years after specific treatment for the disease (MDT) had been completed. Results: Persistence of aPL antibodies among the 38 leprosy patients was 84% (32/38), and all had the IgM isotype. Mean age was 48.1 ± 15.9 years, and 23 (72.0%) were male. The lepromatous form (LL) of leprosy was the most common (n = 16, 50%). Reactional episodes were observed in three patients (9.4%). Eighteen (47.37%) were still taking medication (prednisone and/or thalidomide). Mean IgM levels were 64 U/mL for aCL and 62 U/mL for anti-β2GPI. In the multivariate binary logistic regression the following variables showed a significant association: age (p = 0.045, OR = 0.91 and CI 95% 0.82-0.98), LL clinical presention (p = 0.034; OR = 0.02 and CI 95% = 0.0-0.76) and bacterial index (p = 0.044; OR = 2.74 and CI 95% = 1.03-7.33). We did not find association between prednisone or thalidomide doses and positivity for aPL (p = 0.504 and p = 0.670, respectively). No differences in the variables vascular thrombosis, pregnancy morbidity, diabetes, smoking and alcoholism were found between aPL-positive and aPL-negative patients. Conclusion: Persistence of positivity for aPL antibodies was influenced by age, clinical presentation and bacterial index. However, further studies are needed to elucidate the reason for this persistence, the role played by aPL antibodies in the disease and the B cell lineages responsible for generation of these antibodies.

Análisis de anticuerpos antifosfolipídicos y cistatina C en pacientes con esclerosis múltiple / Analysis of antiphospholipid antibodies and cystatin C in multiple sclerosis patients / Teste de anticorpos antifosfolípídes e cistatina C em pacientes com esclerose múltipla

La cistatina C es considerada el inhibidor fisiológico más importante de las proteasas de cisteína endógenas. Se cree que el papel de la cistatina C es el de modular la actividad de las proteasas secretadas o liberadas de células dañadas o en proceso de necrosis, siendo por tanto las cistatinas fundamentales para los procesos de regulación y prevención del potencial daño proteolítico local. Los anticuerpos antifosfolípidos se usan para esclarecer el diagnóstico de esclerosis múltiple (EM) ya que existen patologías que pueden cursar con sintomatología o hallazgos paraclínicos semejantes. El objetivo de este trabajo fue analizar la concentración de cistatina C y la presencia o ausencia de anticuerpos antifosfolipídicos en pacientes diagnosticados de esclerosis múltiple remitente recurrente (EMRR) como marcadores de desmielinización. Este trabajo se llevó a cabo conjuntamente por el laboratorio de Riesgo Vascular, el laboratorio de Autoinmunidad y la Unidad de Esclerosis Múltiple del Hospital Universitario Virgen Macarena de Sevilla, España, con una duración de un año. Se seleccionaron dos tipos de poblaciones: grupo 1, n=30 pacientes con EMRR y un segundo grupo, denominado grupo control, n=30. Se determinó cistatina C y anticuerpos antifosfolípidos IgG e IgM, anticuerpos anticardiolipina IgG e IgM y anticuerpos f>2 glicoproteína IgG e IgM. Los pacientes diagnosticados de EMRR presentan títulos negativos de anticuerpos antifosfolípidos IgG e IgM, anticardiolipina IgG e IgM y f>2 glicoproteína IgG e IgM. La concentración de cistatina C es menor en el grupo de pacientes diagnosticados de EM, lo que podría producir un déficit en la modulación de las proteasas de cisteína endógenas. Dicha desmielini-zación agudizaría el progreso de la EM.

Cystatin C is considered the most important physiological inhibitor of endogenous cysteine proteases; the role of cystatin C is believed to be to modulate the activity of proteases secreted or released from damaged cells or in the process of necrosis, therefore cystatins being fundamental regulatory processes and a potential prevention of local proteolytic damage. Antiphospholipid antibodies are used to clarify the diagnosis of diseases like multiple sclerosis (MS) and other pathologies could present similai symptoms or paraclinical findings. The objective of the present work is to analyze the concentration of cystatin C and the presence or absence of antiphospholipid antibodies in patients diagnosed with relapsing remitting multiple sclerosis (RRMS) as markers of demyelization. This work was carried out jointly by the Vascular Risk Laboratory, the Laboratory of Autoimmunity and Multiple Sclerosis Unit, Hospital Universitario Virgen Macarena in Seville in one year. Two types of people were selected: Group 1 (n = 30) RRMS group and a control group, n = 30. Cystatin C and antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM were determined. Patients showed negative titers of antiphospholipid antibodies IgG and IgM, IgG and IgM anticardiolipin, $2 glycoprotein IgG and IgM. Cystatin C concentration is lower in the group of patients diagnosed with MS, which could give rise to a decrease in the modulation of endogenous cysteine proteases. This would exacerbate the progress of demyelization in MS.

A cistatina C é considerada o inibidor fisiológico das proteases de cisteína endógenas mais importante. Acredita-se que o papel da cistatina C é o de modular a atividade de proteases secretadas ou liberadas a partir de células danificadas ou em processo de necrose, sendo por isso as cistatinas fundamentais para os processos de regulagao e prevengao do potencial dano proteolítico local. Anticorpos antifosfolípides sao usados para esclarecer o diagnóstico de EM, visto que existem patologias que podem apresentar sintomas ou achados paraclínicos semelhantes. O objetivo deste trabalho foi o de analisar a concentra-gao de cistatina C e a presenga ou ausencia de anticorpos antifosfolípides em pacientes diagnosticados com esclerose múltipla recidivante - remitente (EMRR) como marcadores de desmielinizagao. Este trabalho foi realizado em conjunto pelo laboratório de Risco Vascular, o laboratório de Autoimunidade e a Unidade de Esclerose Múltipla do Hospital Universitario Virgen Macarena, de Sevilha, Espanha, com uma duragao de um ano. Foram selecionados dois tipos de populagdes-. Grupo 1 (n = 30) pacientes com EMRR e um segundo grupo, chamado de grupo controle, n = 30. Determinou-se cistatina C e anticorpos antifosfolípides IgG e IgM, anticorpos anticardiolipina IgG e IgM, e anticorpos $2 glicoproteína IgG e IgM. Pacientes diagnosticados com EMRR apresentam títulos negativos de anticorpos antifosfolípides IgG e IgM, anticardiolipina IgG e IgM e $2 glicoproteína IgG e IgM. A concentragao de cistatina C é menor no grupo de pacientes diagnosticados com EM, o que poderia produzir um déficit na modulagao das proteases de cisteína endógenas. Tal desmielinizagao agravaría o progresso da EM.

Right-to-left shunt and the hypercoagulable state: does paradoxical embolism play a role in patients with antiphospholipid syndrome and stroke? / Shunt direita-esquerda e hipercoagulabilidade: embolia paradoxal pode ser responsável pelo AVC na síndrome antifosfolipídica?

OBJECTIVE: Patent foramen ovale is associated with paradoxical embolism (PE) and stroke. Hypercoagulable states, such as antiphospholipid syndrome (APS), can exacerbate PE by increasing clot formation. The aim of this study was to verify whether patients with APS and stroke present a right-to-left shunt (RLS) with greater frequency than patients with APS but without stroke. METHODS: Fifty-three patients with APS were tested for RLS using contrast-enhanced transcranial Doppler (cTCD): 23 patients had a history of stroke (Stroke Group) and 30 had no history of stroke (No-stroke Group). RESULTS: cTCD was positive in 15 patients (65%) from the Stroke Group and in 16 patients (53%) in the No-stroke Group (p=0.56). The proportion of patients with a small RLS (<10 high-intensity transient sign or HITS) and a large RLS (>10 HITS) was similar between the groups without significant difference. CONCLUSIONS: Our data do not support the theory that paradoxical embolism may play an important role in stroke in APS patients.

OBJETIVO: O forame oval patente está associado com embolia paradoxal e acidente vascular cerebral isquêmico (AVCi). Estados de hipercoagulabilidade, como a síndrome antifosfolipídica (SAF), podem facilitar esse processo, aumentando a formação de coágulos. O objetivo deste estudo foi verificar se pacientes com SAF e AVCi apresentam maior frequência de shunt direita-esquerda (SDE), comparados a pacientes com SAF sem AVCi. MÉTODOS: Cinquenta e três pacientes com SAF foram testados para SDE usando Doppler transcraniano contrastado (DTCc): 23 com AVCi (Grupo AVC) e 30 sem história de AVCi (Grupo Controle). RESULTADOS: DTCc foi positivo em 15 pacientes (65%) do Grupo AVC e em 16 pacientes (53%) no Grupo Controle (p=0,56). A proporção de pacientes com pequeno SDE (<10 HITS) e grande SDE (>10 HITS) foi semelhante nos dois grupos. Não houve diferença significativa entre os grupos. CONCLUSÕES: Nossos dados não sugerem que embolia paradoxal seja causa importante de AVCi em pacientes com SAF.

Prevalencia de anticuerpos antifosfolípidos en pacientes con conectivopatías / Prevalence of antiphospholipid antibodies in patients with connective tissue diseases

Objetivos: Determinar la prevalencia de anticuerpos antifosfolípidos en pacientes con conectivopatías. Diseño: Estudio descriptivo transversal. Institución: Hospital Dos de Mayo e Instituto de Investigaciones Clínicas de la UNMSM, Lima, Perú. Participantes: Pacientes con diagnóstico de colagenopatía y sujetos sanos. Intervenciones: En 100 pacientes con diagnóstico de colagenopatía y 50 sujetos sanos, todos provenientes de Lima Metropolitana y atendidos entre enero y noviembre de 2008, se determinó fibrinógeno, tiempo de protrombina, tiempo parcial de tromboplastina activada, anticuerpos anticardiolipina y anticoagulante lúpico. Principales medidas de resultados: Presencia de anticuerpos anticardiolipina y anticoagulante lúpico. Resultados: Los pacientes con conectivopatías presentaron anticuerpos antifosfolípidos en 17 por ciento, anticoagulante lúpico en 13 por ciento y anticardiolipina IgG 4 por ciento. Al dividir el grupo por conectivopatías, en los 70 pacientes con lupus eritematoso sistémico 10 resultaron positivos para anticoagulante lúpico y 3 tuvieron anticardiolipina IgG; de los 30 pacientes con artritis reumatoide, 3 tuvieron anticoagulante lúpico positivo y 1 presentó anticardiolipina IgG. En el grupo de 50 personas sanas, solo se encontró un caso positivo para anticoagulante lúpico. Conclusiones: La prevalencia de anticuerpos antifosfolípidos en pacientes con conectivopatías fue 17 por ciento. La conectivopatía estudiada más frecuente fue el lupus eritematoso sistémico. El anticuerpo antifosfolípido más frecuente fue el anticoagulante lúpico.

Objectives: To determine the prevalence of antiphospholipid antibodies in patients with connective tissue diseases. Design: Descriptive transversal study. Setting: Dos de Mayo Hospital and Institute of Clinical Research, San Marcos University, Lima, Peru. Participants: Patients with diagnosis of collagen disease and healthy subjects. Interventions: In 100 patients with collagen disease and 50 healthy subjects, all from Metropolitan Lima and attended between January and November 2008, fibrinogen, prothrombin time, partial activated thromboplastin time, anticardiolipin antibody and lupus anticoagulant were determined. Main outcome measures: Presence of anticardiolipin antibodies and lupus anticoagulant. Results: Patients with collagen diseases presented antiphospholipid antibodies in 17 per cent, lupus anticoagulant in 13 per cent, and IgG anticardiolipin in 4 per cent. Individualizing connective tissue diseases, in 70 patients with systemic erythematous lupus 10 were positive for lupus anticoagulant and 3 had IgG anticardiolipin; of 30 patients with rheumatoid arthritis three were positive to lupus anticoagulant and one presented IgG anticardiolipin. In the group of 50 healthy individuals, only one was positive for lupus anticoagulant. Conclusions: The prevalence of antiphospholipid antibodies in patients with connective tissue was 17 per cent. The most frequent connective tissue disease studied was lupus erythematosus and the most frequent antiphospholipid antibody found was lupus anticoagulant.

Usefulness of Silica Clotting Time for Detection of Lupus Anticoagulants / 대한진단검사의학회지

BACKGROUND: The presence of lupus anticoagulants (LA) is a strong risk factor for thrombosis in antiphospholipid syndrome. We investigated the usefulness of addition of silica clotting time (SCT) to the pre-existing dilute Russell's viper venom test (dRVVT) for detection of LA. Also, we analyzed differences in the thrombotic features and the characteristics of antiphospholipid antibodies between dRVVT and SCT. METHODS: A total of 167 patients positive for LA or anti-cardiolipin (anti-CL) antibody and 76 healthy controls were enrolled. The dRVVT and SCT were used for detection of LA. Anti-CL, anti-beta2-glycoprotein I (anti-beta2 GPI) and anti-prothrombin (anti-PT) antibodies were measured using commercial ELISA kits. RESULTS: In detection of thrombosis, the sensitivity of the combined test of SCT and dRVVT was 56.4%, which was higher than that of dRVVT alone (46.2%) or SCT alone (23.1%). The specificity of the combined test (80.9%) was comparable to that of dRVVT (81.9%). Also, odds ratio for predicting thrombosis was higher in the combined test than in dRVVT or SCT alone. When normalized LA ratio of the two tests was compared, the group of patients with higher ratio of SCT showed significantly higher prevalence of recurrent abortion and higher positivity of IgG types of anti-CL, anti-beta2 GPI and anti-PT than the group with higher ratio of dRVVT. CONCLUSIONS: Addition of SCT to dRVVT can improve the detection sensitivity of thrombosis in LA test. And the high normalized LA ratio of SCT may be a useful parameter for detection of recurrent abortion.

Asociación entre anticuerpos antifosfolípidos y complicaciones de la gestación en mujeres de Costa Rica / Association between antibodies antiphospholipids and complications of the gestation in women of Costa Rica

Objetivo: Determinar asociación entre los anticuerpos antifosfolípidos y complicaciones de la gestación (aborto de cualquier tipo, preeclampsia, eclampsia, insuficiencia placentaria grave o parto antes de la semana 34 de gestación), tomando como base la población de pacientes del servicio de Obstetricia del Hospital México. Materiales y métodos: Estudio de casos y controles en la población de pacientes atendidas por el servicio de Obstetricia del Hospital México en el período comprendido entre enero de 2002 y diciembre de 2004. Se tomaron los datos del registro de egresos Hospitalarios, se hizo un análisis descriptivo, y un análisis univariado y multivariado de las principales variables registradas. Resultados: El promedio de edad de las pacientes en los casos y los controles no mostró diferencia significativa. La provincia de San José reporta el mayor porcentaje de casos con un 39.9 por ciento, seguido por Heredia con un 26.8 por ciento y Alajuela con un 24.6 por ciento. En cuanto al número de gestaciones, se determinó que no influyen significativamente en relación con el aborto y otras complicaciones de la gestación. El análisis univariado y multivariado mantiene asociación entre los antecedentes clínicos de las gestaciones anteriores, además de los anticuerpos antifosfolípidos respecto al aborto y otras complicaciones de la gestación. Conclusión: Los anticuerpos antifosfolípidos deberían ser tomados en cuenta como parte del seguimiento del embarazo en pacientes con historia de abortos y complicaciones de la gestación en embarazos previos.

Hipertension pulmonar tromboembolica cronica con y sin sindrome antifosfolipido / Chronic thromboembolic pulmonary hypertension with and without antiphospholipid syndrome

La hipertensión pulmonar tromboembólica crónica (HPTC) está dada por la obstrucción de arterias pulmonares y sus ramas por trombos organizados. El objetivo fue evaluar las características y evolución de la HPTC en pacientes con y sin síndrome antifosfolípido (SAF). Se analizaron retrospectivamente todos los pacientes con HPTC en nuestra institución entre junio de 1993 y junio del 2005. De los 38 pacientes evaluados, 16 tenían SAF (grupo A) y 22 pacientes (grupo B) presentaban estudio de trombofilia normal (n = 10) u otras anormalidades trombofílicas (n = 12). Ambos grupos fueron similares en cuanto a la media de edad (41 vs. 50 años), la clase funcional que presentaban al diagnóstico (81 vs. 100% en clase III-IV), y la presencia de trombosis en otros territorios (31 vs. 27%). El 62.5% de pacientes del grupo A y el 54.5% del grupo B fueron sometidos a tromboendarterectomía pulmonar. La media de seguimiento fue de 45 meses (rango de 0.5 a 144). Al final del mismo todos los pacientes con SAF y todos los pacientes operados estaban en clase funcional I-II. La mediana de sobrevida desde el momento del diagnóstico alcanzó los 59 meses para el grupo A vs. 27 meses en el grupo B (p = 0.199). La media de sobrevida del total de los pacientes operados fue de 56 meses para el grupo A vs. 33 meses para el grupo B (p = 0.08). En conclusión: Los pacientes con HPTC y SAF tendieron a lograr una mejor sobrevida que los pacientes con HPTC sin SAF. Aquellos con HPTC y SAF que fueron operados lograron mejoría de su clase funcional y tendieron a una mayor sobrevida respecto de los no operados.

Chronic thromboembolic pulmonary hypertension (CTE-PH) is defined as the chronic obstruction by organized thrombi in pulmonary artery and their branches causing pulmonary hypertension. The objective is to evaluate features and outcome of CTE-PH in patients with and without coexisting antiphospholipid syndrome (APS). All patients studied at our Institution with CTE-PH between June 1993 and June 2005 were analyzed retrospectively. Sixteen out of 38 patients were APS positive (group A), and 22/38 patients (group B) disclosed normal results (n = 10) or other thrombophilic abnormalities (n =12). Results: both groups were similar in age (mean 41 vs. 50 years), NYHA class at diagnosis (81 vs. 100% in III-IV) and the presence of previous or coexistent thrombosis in other territories (31 vs. 27%). Sixty three percent of patients in group A and 55% of patients in group B underwent thromboendarterectomy. The patients were followed during an average of 45 months (0.5- 144). At the end of follow up all the APS patients and all the chirurgical patients were in I-II functional class (p=0.053). The median survival from diagnosis was 59 months for group A and 27 months for group B (p=0.199). The mean survival of patients who underwent thromboendarterectomy was 56 months for group A vs. 33 months for group B (p=0.08). We conclude that patients with CTE-PH and APS disclosed a trend to a better survival than patients with CTE-PH without APS. Those patients with CTE-PH and APS who underwent thromboendarterectomy tended to achieve a better functional class and survival than those who received medical treatment.

Significance of antiphospholipid antibodies in lupus nephritis.

BACKGROUND: Some autoantibodies have been associated with lupus nephritis but the role of antiphospholipid antibodies (APA) is controversial. OBJECTIVE: The present study was to explore the role of APA by comparing demographic profiles and the presence of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in systemiclupus erythematosus 1 (SLE) patients with and without nephritis. MATERIAL AND METHOD: The cross-sectional study in a tertiary center was conducted in 77 SLE patients. All patients attended our renal or rheumatology clinics between June 2002 and December 2003. RESULTS: Sixty-three (82%) of the 77 SLE patients had nephritis. The prevalence of antiphospholipid syndrome (APS) was 10% (8 patients), positive aCL (IgG) was 26% (20 patients) and positive LA was 26% (20 patients). The receiver operating characteristic (ROC) method was applied to assess the significance of aCL in both nephritis and non-nephritis groups. Area under the ROC curve was 0.538 (95%CI 0.312-0.765), a cutoff value of 20.5 GPL had a sensitivity of 75% and a specificity of 53%. In univariate analysis, neither positivity for anticardiolipin antibody nor lupus anticoagulant was associated with lupus nephritis. Analyzed in only the lupus nephritis group, LA-positive lupus nephritis patients had higher systolic blood pressure (SBP) (133.7 vs 121.9 mmHg, p = 0.005), lower platelet count (209.8 vs 264.4 x 10(3)/microL, p = 0.02) and higher 24-hr urine protein excretion (2.6 vs 1.4 g, p = 0.02) than LA-negative lupus nephritis patients. Serum creatinine was higher in LA-positive lupus nephritis than LA-negative (233.0 vs 94.9 micromol/L), but did not reach statistical significance. CONCLUSION: APA are frequently seen in SLE patients, but not associated with lupus nephritis. However lupus anticoagulant tends to associate with lupus nephritis. Detection of LA in lupus nephritis patients could identify patients who had increased risk to develop bad renal outcomes (elevated SBP and 24-hr urine protein excretion).

Frequency of antiphospholipid antibodies in patients with infectious diseases using three different ELISA methods

OBJETIVO: O ensaio de enzyme-linked immunosorbent assay (ELISA) para a pesquisa de anticorpos anticardiolipina (aCL) é o mais importante teste para o diagnóstico da síndrome antifosfolipídica (SAF). Entretanto esse teste também pode ser positivo em algumas doenças infecciosas. Tem sido sugerido que a detecção de anticorpos para uma mistura de fosfolípides ou para b2-glicoproteína I (b2-GP I) teria uma maior especificidade para a SAF que o teste de ELISA-padrão para aCL. O objetivo do presente estudo é comparar a especificidade de três testes para anticorpos antifosfolípides (aFL) em pacientes com doenças infecciosas. MÉTODOS: Anticorpos antifosfolípides foram pesquisados por três técnicas de ELISA, ou seja, o teste-padrão para aCL, o kit de ELISA APhL® e o teste para anti-b2-GP I em pacientes com doenças infecciosas, tais como sífilis (69), leptospirose (33) e Calazar (30). RESULTADOS: A freqüência de positividade de aFL da classe IgG em pacientes com sífilis, leptospirose e Calazar foi de 13/69 (19 por cento), 9/33 (27 por cento) e 2/30 (6 por cento), respectivamente, com o ELISA-padrão para aCL versus 1/69 (1,4 por cento), 0/33 (0 por cento) e 0/30 (0 por cento) com o kit de ELISA APhL®. A positividade do isotipo IgM foi de 10/69 (14 por cento), 4/33 (12 por cento) e 1/30 (3 por cento), respectivamente, com o ELISA-padrão para aCL, e 1/69 (1,4 por cento), 0/33 (0 por cento) e 0/30 (0 por cento) com o kit de ELISA APhL®. Anticorpos da classe IgG contra b2GPI foram detectados em 14/69 casos de sífilis (20 por cento), 6/33 casos de leptospirose (18 por cento) e 16/30 casos de Calazar (53 por cento). Assim, o kit de ELISA APhL® apresentou uma maior especificidade: 97 por cento (95 por cento CI: 92 por cento-99 por cento) comparado com 81 por cento (95 por cento CI: 74 por cento-87 por cento) para o teste de aCL-padrão e 72 por cento (95 por cento CI: 64 por cento-79 por cento) para o teste de anticorpos anti-b2 GPI. CONCLUSÕES: O kit de ELISA APhL® parece ser m...

Evaluation of anticardiolipin antibodies and antiphosphatidylserine antibodies in women with recurrent abortion.

BACKGROUND: Antiphospholipid syndrome (APS) is a major reproductive complication in women, which is characterized by recurrent fetal loss, thrombosis, and thrombocytopenia in association with anticardiolipin antibodies (aCL). AIMS: To analyze the prevalence of aCL and antiphosphatidylserine antibodies (aPS) in relation to pregnancy failures in women with the history of recurrent spontaneous abortion. SETTINGS AND DESIGN: A sequential study of 155 patients, who had three or more recurrent spontaneous abortions, was carried out. METHODS AND MATERIALS: Women with unexplained recurrent pregnancy loss in first trimester were selected for this study. Anticardiolipin antibodies IgG and aPS IgG were detected in the serum by the enzyme linked immunosorbent assay method. STATISTICAL ANALYSIS: Percentage calculation was carried out. Two-tailed t-test was performed to know the significance of aCL and aPS total population. RESULT: The levels of aCL IgG and aPS IgG were detected as 40% (62) and 19% (18), respectively in women with history of recurrent abortion. CONCLUSION: Anticardiolipin antibody is found to be the most important factor for recurrent abortion. In addition, women with negative aCL are having positive for another antiphospholipid antibodies like aPS, which may involve in recurrent abortion.

relationship between precence of antiphospholipid antibodies in pregnant womens' serum and preeclampsia

Antiphospholipid antibodies may be detected in normal pregnancies and may cause thrombosis, recurrent fetal loss, placental infarction and preeclampsia. In this study the possible differences in antiphospholipid antibody titer between healthy pregnant women and preeclampsic cases was examined. The antiphospholipid antibody titer in 50 healthy pregnant women with 50 preeclampsia cases without the history of thrombosis and autoimmune disease was compared. IgG and IgM anticardiolipin antibody was measured by immunoassay methods. Teclot kits were used for Lupus-like anticoagulant antibodies. Data was analyzed by Chi-square test, p<0/05 was considered significant. There was no association between antiphospholipid antibody titer in healthy and preecalamptic group. In normal pregnant women and preeclamptic cases there was 6% and 8% Lupus like anticoagulant antibody, 12% and 4% IgG anticardiolipin antibody and 26% and 30% IgM anticardiolipin antibodies respectively. Despite the evidence of prothrombotic state during preeclampsia, it is unlikely that antiphospholipid antibodies represent a risk factor for preeclamptic women as compared to healthy pregnant women

Anticardiolipin antibodies in young Iraqi adults with deep venous thrombosis

To determine the prevalence and clinical significance of anticardiolipin antibodies [ACA] in young Iraqis with Deep venous thrombosis [DVT]. A total of 50 unselected young Iraqi adults [<45 years] with Doppler confirmed DVT were evaluated. The evaluation included full relevant history, Prothrombin Time, Partial Thromboplastin Time, Kaolin Clotting time [KCT], KCT index [to screen for Lupus Anticoagulant [LA] in patients not on oral anticoagulants], and lgG and IgM ACA titres [by ELISA]. The median age of the DVT patients was 32.5 years with a M:F ratio of 1:2.6. The overall prevalence of Antiphopholipid Antibodies [APA] [those with elevated ACA and/or LA] was 16%, while it was 9.5% in the subcategory with single DVT attack. The subcategory of patients with recurrent DVT [8 patients] had significantly higher frequency of APA [OR 9.5] and lgG ACA titres compared to those with a single episode [p=0.01583 and 0.01 respectively]. Higher frequencies of APA were also encountered in the subcategories with history of Pulmonary embolism, Stroke and recurrent fetal loss, compared to those without such histories [OR of 3.2, 6.7 and 7.7 respectively]. The findings of this study are consistent with worldwide reports on prevalence and significance of APA. The high frequency of these antibodies in young Iraqi patients and their association with recurrent thrombotic events, in addition to the bulk of the literature suggesting higher recurrence rates and mortality in those with the antibodies on cessations of therapy, warrants pursuing the policy of evaluating all Iraqi young adults at diagnosis or just prior stopping therapy for APA, and considering long term appropriate anticoagulation in those with the antibodies, to reduce recurrence and mortality

Estudio interlaboratorio de los ensayos para anticuerpos antifosfolípidos / Cooperative study for Interlaboratory antiphospholipid antibodies detection

La presencia de anticuerpos antifosfolípidso (aFL) en pacientes con trombosis venosa y/o arterial, pérdidas fetales o abortos recurrentes caracteriza al síndrome antifosfolípido (SAF). Los aFL son evaluados por métodos convencionales como ensayos de coagulación para la actividad de anticoagulante lípico (AL) y ensayos inmunológicos para los anticuerpos anticardiolipina (aCL). Aún existen muchos inconvenientes cuando se comparan los resultados informados por distintos laboratorios a pesar de los avances logrados en la estandarización de estos ensayos. El comité de Síndrome Antifosfolípido del grupo CLART realizó un estudio interlaboratorio que consistió en dos etapas: 1) distribución de un cuestionario para conocer la metodología utilizada por los centros participantes en la evaluación de los aFL, 2) distribución y análisis de 12 muestras de sueros para determinar la concordancia de los resultados de aCL dados por los participantes con aquellos considerados de referencia determinados por el centro coordinador. Se recibieron en la primera etapa 27 respuestas y en la segunda, los resultados de 20 de los 24 centros que acordaron participar. Se observó una gran dispersión de los resultados para a CL, IgG e IgM (principalmente usando equipos comerciales) en comparación con los de referencia (ELISA desarrollado), considerando tanto los valores en unidades como en títulos. La concordancia entre los resultados mejoró significativamente cuando los datos de aCL de los participantes eran agrupados como resultado negativo (título negativo o positivo débil) o positivo (título positivo moderado o alto) para el SAF. Esto remarca la necesidad de una mejor estandarización y de urgentes recomendaciones internacionales para la realización del ensayo de aCL, parte fundamental de los criterios de laboratorio para el SAF.

Pseudotumor syndrome associated with antiphospholipid antibodies and cerebral venous sinus thrombosis.

Antiphospholipid antibodies have been recognized as a marker for an increased risk of thrombosis, including cerebral venous thrombosis. This is a clinical study of three patients who presented with features of raised intracranial tension. Investigations revealed normal CT of brain and CSF examination in two patients. MRI of brain revealed dural venous sinus thrombosis in all the patients and positive antiphospholipid antibodies in the blood. All patients recovered with anticoagulant therapy. Antiphospholipid antibodies should be considered in the differential diagnosis of pseudotumor syndrome related to cerebral venous thrombosis.

Livedo vasculitis con ulceraciones de verano / Livedo Vasculitis, with sommer ulcers

Se presenta una paciente con lesiones ulcerosas en miembros inferiores. Al interrogatorio y análitica sanguínea se detectan otras enfermedades que la paciente ignora, entre ellas un sindrome anticuerpo antifosfolipídico (SAAF). Se describe la afección y su relación con etioligías que se hace obligatoriobuscar ante este cuadro clínico.

Movimentos involuntários anormais como primeira manifestaçäo do lupus eritematoso sistêmico: relato de caso / Involuntary movement disorders as first manifestation of systemic lupus erythematosus: case report

Relatamos o caso de uma paciente, de 36 anos de idade, que desenvolveu quadro de coréia após dois meses do início do uso de anticoncepcional oral, acompanhando-se, posteriormente, de trombocitopenia, úlcera mucosa em cavidade oral, artrite, positividade para os anticorpos antinuclear (FAN), anti-DNA e anti-Sm, preenchendo critérios para lúpus eritematoso sistêmico, segundo o Colégio Americano de Reumatologia. A pesquisa para os anticorpos anticoagulante lúpico e anticardiolipina (IgG e IgM) foi negativa. A paciente foi tratada com prednisona, fenitoína, fenobarbital e clonazepam, obtendo melhora clínica e laboratorial. Discutimos a ocorrência da coréia e outros movimentos anormais como primeira manifestação do lúpus eritematoso sistêmico, sua relação com os anticoncepcionais orais e os anticorpos antifosfolípides.