Validation of the adjusted global antiphospholipid syndrome score in systemic lupus erythematosus patients in Argentina.

INTRODUCTION: Assessment of risk both for pregnancy morbidity and thrombosis in the presence of anti-phospholipid antibodies (aPL) is still a challenge in Systemic Lupus Erythematosus (SLE) patients. The Global Antiphospholipid Syndrome Score (GAPSS) takes into account the aPL profile (criteria and non-criteria aPL), the conventional cardiovascular risk factors and the autoimmune antibody profile. An adjusted model of the score (aGAPSS) excluding anti-phosphatidylserine/Prothrombin (aPS/PT), suggests that the score is able to stratify patients for their rate of events making it widely applicable in daily clinical practice. OBJECTIVE: To validate the aGAPSS in a multicentric cohort of SLE patients in Argentina. PATIENTS AND METHODS: consecutive SLE patients with and with andwithout thrombotic events from seven Rheumatologist centers were included. Traditional cardiovascular risk factors, aPL antibodies and medications received (aspirin, hydroxychloroquine and anticoagulation) were collected. The score aGAPSS was calculated for each patient at the last visit by adding together the points corresponding to the risk factors: 1 for hypertension, 3 for dyslipidemia, 4 for LA and B2GPI (IgM or IgG) antibodies and 5 for aCL (IgM or IgG) antibodies. The discriminative ability of the aGAPSS was calculated by measuring the area under the receiver operating characteristic curve (AUC). Multivariate logistic regression analysis was performed to examine the impact of multiple cardiovascular risk factors and laboratory parameters on the occurrence of thrombosis. RESULTS: Two hundred and ninety-six SLE patients were included. One-hundred and twenty-one patients (40.9%) presented thrombotic and/or pregnancy complications. Median aGAPSS was significantly higher in patients who experienced an event (thrombosis and/or pregnancy morbidity) compared with those without [4 (IQR 1-9) versus 1 (IQR 0-5); p < 0.001]. The best cut off point for the diagnosis of thrombosis and/or pregnancy complications was aGAPSS ≥4. Multivariate logistic regression analysis showed that aCL antibodies [OR 2.1 (95% CI 1.16-3.90); p = 0.015] were an independent risk factors for thrombotic events. CONCLUSIONS: This score is a simple tool, easy to apply to SLE patients in daily practice. The use of the aGAPSS could change the non-pharmacologic and pharmacologic treatment in higher risk patients to improve their survival.

Sub-segmental pulmonary thromboembolism in a pregnant woman with generalized lupus erythematosus, triple-negative antiphospholipid syndrome, and protein C deficiency. A case report.

Autoimmune diseases and thrombophilic disorders, notably antiphospholipid syndrome (APS) and protein S deficiency, present a formidable challenge in pregnancy, substantially increasing the risk of thromboembolic complications by up to 20%. Pulmonary thromboembolism (PTE), characterized by a significantly higher maternal mortality rate, is of particular concern. APS, defined by the presence of antiphospholipid antibodies, emerges as a pivotal risk factor for PTE during pregnancy, especially in women exhibiting triple negativity. Concurrently, protein S deficiency further amplifies vulnerability to thromboembolic events, establishing a high-risk scenario for pregnant individuals. In a case involving a 29-year-old pregnant woman with a history of generalized lupus erythematosus, triple-negative antiphospholipid syndrome, and protein S deficiency, sudden-onset dyspnea prompted thorough investigation. Despite her complex medical history, a multidisciplinary approach led to the accurate diagnosis and successful management of subsegmental pulmonary thromboembolism, ensuring the well-being of both mother and fetus. Effectively managing PTE during pregnancy demands a comprehensive, multidisciplinary approach involving collaboration among obstetricians, internists, rheumatologists, and hematologists. Accurate diagnosis, tailored anticoagulation strategies, and continuous monitoring stand as indispensable pillars for maternal and fetal well-being.

Diagnóstico y tratamiento clínico del síndrome antifosfolipídico seronegativo / Diagnostic and clinical treatment of seronegative antiphospholipid syndrome / Diagnóstico e tratamento clínico da síndrome antifosfolípide soronegativa

El Síndrome antifosfolipídico (SAF) se describió por primera vez en el año de 1982 por el científico Graham R. V Hughes. En el año 2003 Hughes y Khamasht lograron identificar una variable poco común de SAF denominada seronegativa, la cual se manifiesta con el cuadro trombolítico característico de esta enfermedad sin embargo existe ausencia de positividad en las pruebas serológicas, debido a que es una patología de difícil identificación y diagnóstico requiere de especial atención puesto que puede conllevar a múltiples complicaciones al no ser tratada de manera oportuna. Objetivo. Describir el diagnóstico y tratamiento del Síndrome Antifosfolipídico Seronegativo. Metodología. Se realizó una revisión sistemática donde se incluyeron estudios originales, metaanálisis y experimentales con fecha de publicación de los últimos 5 años en idioma inglés y español. Se utilizaron bases de datos virtuales como Pubmed, Scielo y Google Scholar. Conclusión. El Síndrome antifosfolipídico seronegativo una patología de difícil reconocimiento debido a la negatividad que refleja en las pruebas serológicas, para el diagnóstico inicialmente se debe tomar en cuenta las manifestaciones clínicas del paciente para obtener una sospecha, posterior a ello, es importante la realización de pruebas serológicas en donde primero se realice la detección de anticuerpos que forman parte de los criterios de SAF.

Antiphospholipid syndrome (APS) was first described in 1982 by the scientist Graham R. V Hughes. In 2003 Hughes and Khamasht managed to identify an uncommon variable of FAS called seronegative, which manifests with the characteristic thrombolytic picture of this disease however there is absence of positivity in serological tests, because it is a pathology of difficult identification and diagnosis requires special attention since it can lead to multiple complications if not treated in a timely manner. Objective. To describe the diagnosis and treatment of Seronegative Antiphospholipid Syndrome. Methodology. A systematic review was carried out including original studies, meta-analysis and experimental studies published in the last 5 years in English and Spanish. Virtual databases such as Pubmed, Scielo and Google Scholar were used. Conclusion. Seronegative antiphospholipid syndrome is a pathology that is difficult to recognize due to the negativity reflected in serological tests. For diagnosis, the clinical manifestations of the patient should be taken into account initially to obtain a suspicion, after which it is important to carry out serological tests in which the detection of antibodies that are part of the criteria for FAS should be performed first.

A síndrome antifosfolipídica (SAF) foi descrita pela primeira vez em 1982 pelo cientista Graham R. V Hughes. Em 2003, Hughes e Khamasht conseguiram identificar uma variável rara da SAF denominada soronegativa, que se manifesta com o quadro trombolítico característico dessa doença, porém há ausência de positividade nos testes sorológicos, pois se trata de uma patologia de difícil identificação e o diagnóstico requer atenção especial, uma vez que pode levar a múltiplas complicações se não for tratada em tempo hábil. Objetivo. Descrever o diagnóstico e o tratamento da Síndrome do Anticorpo Antifosfolípide Soronegativo. Metodologia. Foi realizada uma revisão sistemática incluindo estudos originais, meta-análises e estudos experimentais publicados nos últimos 5 anos em inglês e espanhol. Foram utilizados bancos de dados virtuais como Pubmed, Scielo e Google Scholar. Conclusão. A síndrome antifosfolípide soronegativa é uma patologia de difícil reconhecimento devido à negatividade refletida nos testes sorológicos. Para o diagnóstico, inicialmente devem ser levadas em conta as manifestações clínicas do paciente para obter uma suspeita e, em seguida, é importante realizar testes sorológicos nos quais se realiza primeiro a detecção de anticorpos que fazem parte dos critérios da SAF.

Manifestaciones clínicas y desenlaces maternos y perinatales en gestantes con síndrome antifosfolípido obstétrico de una institución de alta complejidad: estudio descriptivo / Clinical manifestations and maternal and perinatal outcomes in expectant mothers with obstetric antiphospholipid syndrome at a high complexity institution: Descriptive study

RESUMEN Objetivo: Describir las características clínicas, así como los desenlaces maternos y perinatales en gestantes con síndrome antifosfolípido en una institución de alta complejidad. Materiales y métodos: Estudio descriptivo retrospectivo que evaluó gestantes con síndrome antifosfolípido según criterios de Sidney o según criterio de reumatólogo entre 2010 y 2016. Se excluyeron aquellos casos con trombofilias hereditarias, incompetencia cervical o con antecedente de hepatitis B, hepatitis C y virus de inmunodeficiencia humana. La información se recolectó a partir de la revisión de historias clínicas. Resultados: Se incluyeron 16 gestantes; 7 (43,8%) pacientes tenían antecedente de aborto, 5 (71,4%) en más de una ocasión; estas pérdidas ocurrieron después de la semana 10. Nueve (56,3) tenían síndrome antifosfolípido asociado a lupus eritematoso sistémico; el principal marcador serológico fue el anticoagulante lúpico en 12 (75%) gestantes. Dos (12,5%) pacientes tenían triple positividad y 6 (37,5%) doble positividad de anticuerpos antifosfolípidos. Las complicaciones obstétricas más frecuentes fueron: rompimiento prematuro de membranas (28,6%), preeclampsia (13,3%) e insuficiencia placentaria (11,8%), las cuales se presentaron más en pacientes con lupus eritematoso sistémico, así como en aquellas con triple y doble positividad de anticuerpos antifosfolípidos. Conclusiones: En esta cohorte, el síndrome antifosfolípido obstétrico estuvo asociado a lupus eritematoso sistêmico en la mayoría de los casos; sin embargo, éste último estaba en remisión. Los peores desenlaces obstétricos se observaron en pacientes con síndrome antifosfolípido y lupus, o en los casos que tenían triple o doble positividad de anticuerpos antifosfolípidos.

ABSTRACT Objective: To describe the clinical characteristics, as well as the maternal and perinatal outcomes in pregnant women with the antiphospholipid syndrome in a reference institution. Materials and methods: A retrospective descriptive study was carried out in order to evaluate pregnant women with antiphospholipid syndrome according to Sydney criteria or rheumatologist criteria between 2010 and 2016. Cases with hereditary thrombophilia, cervical incompetence, history of hepatitis B, hepatitis C, and human immunodeficiency virus were excluded. The information on sociodemographic and clinical variables was collected from the review of medical records. Results: Sixteen pregnant women were included; seven (43.8%) patients had a history of abortion, five (71.4%) on more than one occasion; these losses occurred after week ten. Nine (56.3) had antiphospholipid syndrome associated with systemic lupus erythematosus. The main serological marker was lupus anticoagulant in 12 (75%) pregnant women. Two (12.5%) patients had triple positivity and six (37.5%) double positivity of antiphospholipid antibo-dies. The most frequent obstetric complications were premature rupture of membranes (28.6%), pre-eclampsia (13.3%), and placental insufficiency (11.8%), which were more com-mon in patients with systemic lupus erythematosus, as well as in those with triple and double antiphospholipid antibody positivity. Conclusions: Obstetric antiphospholipid syndrome was associated with systemic lupus erythematosus in the majority of cases; however, the latter was in remission. The worst obstetric outcomes were observed in patients with this association or in cases with triple or double antiphospholipid antibody positivity.

Uso de inhibidores directos del factor Xa en síndrome antifosfolípido: una serie de 7 casos / Use of factor Xa inhibitors in antiphospholipid antibodies syndrome: A serie of 7 cases

RESUMEN Introducción: El síndrome antifosfolípido se caracteriza por la presencia de anticuerpos contra fosfolípidos de membrana y manifestaciones clínicas, principalmente trombóticas y obstétricas. Su tratamiento se basa en la anticoagulación indefinida, generalmente con warfarina, la cual, por diversos factores, no siempre es factible por lo que es necesario el uso de terapias alternativas. Objetivo: Describirla experiencia con rivaroxabán en pacientes con síndrome antifosfolípido. Materiales y métodos: Estudio descriptivo en el que se evaluaron pacientes que cumplieron los criterios de Sydney de 2006 para síndrome antifosfolípido y que recibieron anticoagulación con rivaroxabán a dosis de 20 mg día en 2 hospitales de referencia en Medellín (Colombia), entre enero de 2012 y abril de 2015. Resultados: Se incluyeron 7 pacientes con una media de edad de 36,6 ± 10,8 arios (rango: 2355). De estos, 4 individuos tenían trombosis venosa, 5 trombosis arteriales, 5 anticuerpos anticardiolipinas positivos, 3 anticoagulante lúpico positivo, 2 pacientes tenían anti-f32 glicoproteína positivo y un paciente triple positividad de anticuerpos. La mediana de utilización de la warfarina fue de 15 meses (rango: 1-36). Las razones para el inicio de rivaroxabán fueron: sangrado (n = 2), rango subterapéutico de anticoagulación (n = 2), toxicodermia (n = 1), intolerancia gastrointestinal (n = 1) y retrombosis (n = 1). El tiempo de uso fue 17,9 ± 13,4 meses (rango: 3-34) y durante el periodo de seguimiento no se presentaron eventos adversos, pero sí 2 episodios nuevos de trombosis. Conclusión: El uso de inhibidores del factor Xa en una serie de pacientes con síndrome antifosfolípido e imposibilidad para el uso de warfarina mostró un adecuado perfil de seguridad; no obstante, hubo 2 episodios recurrentes de trombosis.

ABSTRACT Background: Antiphospholipid syndrome is an autoimmune disease with antibodies against membrane phospholipids with mainly thrombotic and/or obstetric manifestations. Its treatment is generally based on indefinite anticoagulation, usually with warfarin, and which, for various factors, is not always feasible, making it necessary to use alternative therapies. Objective: To describe the experience with rivaroxaban in patients with antiphospholipid syndrome. Materials and methods: A descriptive study was conducted on subjects that met the 2006 Sydney criteria for antiphospholipid antibodies syndrome and received anticoagulation with rivaroxaban at 20mg daily dose in 2 reference hospitals in Medellin, Colombia, between January 2012 and April 2015. Results: The study included 7 patients, with a mean age of 36±10.8 years (range 23-55). Four patients had venous thrombosis, 5 arterial, 5were positive for anticardiolipin antibodies, 3 reactive to lupus anticoagulant, 2 anti-β2 glycoprotein positive subjects, and one patient had triple antiphospholipid antibody positivity. The median time of warfarin use was 15 months (RIQ 1-36). The reasons for starting rivaroxaban were: bleeding (n = 2), sub-therapeutic coagulation ranges (n = 2), toxicoderma, gastrointestinal intolerance, and re-thrombosis (n = 1, each). The time of use was 17.9±13.4 months (range: 3-34). There were 2 recurrent cases of thrombosis during follow-up, and no adverse events. Conclusion: The use of factor Xa inhibitors in a series of patients with antiphospholipid syndrome and unable to use warfarin showed an adequate safety profile; however, 2 recurrent episodes of venous thrombosis occurred.

Trombosis de senos venosos cerebrales asociado a síndrome antifosfolípidos en un paciente pediátrico / Cerebral sinovenous thrombosis associated with antiphospholipid syndrome in a pediatric patient

La trombosis de senos venosos cerebrales es un evento relativamente infrecuente en la población pediátrica. Su origen se ha asociado a múltiples condiciones y factores de riesgo como infecciones locales o sistémicas, malformaciones cardíacas, trauma, deshidratación, enfermedades crónicas y, en especial, a factores genéticos protrombóticos. La localización puede variar dependiendo de la etiología; además, puede cursar con una amplia variabilidad de signos y síntomas dependiendo de la edad del paciente. Se presenta el caso de un paciente masculino de 5 años, que desde los 2 años de edad presenta episodios de cefalea y ataxia de forma intermitente, con autorresolución. Posterior a un evento presenta crisis tónico-clónica del hemicuerpo derecho, seguida de un estado epiléptico súper refractario. En la neuroimagenes (RNM-angioresonancia) se evidencia trombosis de senos venosos cerebrales asociada a un accidente cerebrovascular isquémico en el globus pallidus, el mesencéfalo y los hemisferios cerebelosos. El paciente presenta el anticuerpo anticardiolipina IgM y es positivo para anticoagulante lúpico. Hematología y reumatología pediátrica confirman el diagnóstico de trombosis de senos venosos cerebrales secundario a síndrome antifosfolípidos. El paciente logra mejoría clínica con la implementación de inmunoterapia más anticoagulación.

Cerebral sinovenous thrombosis is a relatively rare disorder in the pediatric population, it has been associated with multiple conditions and risk factors such as local or systemic infections, cardiac malformations, trauma, dehydratation, chronic diseases and especially genetic prothrombotic factors. The location may vary depending on the etiology and may occur with a wide variability in symptoms and signs depending on the age of the patient. Case: 5 year-old male patient, with episodes of self-resolving headache and intermittent ataxia starting at 2 years of age. The patient later presents focal motor seizures, followed by a super refractory status epilepticus. The magnetic resonance imaging (brain MRI and magnetic resonance angiography) shows evidence of a partial cerebral venous deep sinus thrombosis associated with ischemic stroke in globus pallidus, midbrain and cerebellar hemispheres. The patient is positive for IgM anticardiolipin antibody and lupus anticoagulant, where pediatric rheumatology and hematology confirmed diagnosis of cerebral venous sinus thrombosis secondary to antiphospholipid syndrome. Clinical improvement was achieved by implementing immunotherapy plus anticoagulation.