COVID-19 coagulopathy and antiphospholipid syndrome

The presence of thrombotic events in COVID-19 patients has been described since the beginning of the pandemic. This association has been confirmed in most of the reported studies. Autopsy reports have shown that most thromboses are located in the lung, although they have also been observed in other organs such as the skin and kidneys. SARS-CoV2 infection induces a generalized prothrombotic state, which is attributed to a combination of factors such as hypoxia, excess cellular apoptosis, and mainly to overactivation of the immune system. Among immune-mediated prothrombotic situations, antiphospholipid syndrome (APS) stands out. Recurrent thrombotic events are observed in APS in the presence of antiphospholipid antibodies (aPL). There are numerous studies that report high prevalence of aPL in patients with COVID-19 infection. However, the results show discrepancies in the data on the prevalence of aPL, and its role in the pathogenesis of thrombosis in these patients. This could be due to the heterogeneity of the detection procedures for aPL or to transient elevations of non-pathogenic aPL levels in the context of infection. In this review we try to clarify the role of aPL in COVID-19 infection, and attempt to answer the question of whether it is a coagulopathy of its own, or secondary to APS.

La presencia de eventos trombóticos en los pacientes con COVID-19 se describió desde el inicio de la pandemia, asociación que ha sido confirmada en la mayoría de los estudios reportados. Los informes de necropsias han puesto de manifiesto que la mayoría de las trombosis se localiza en el pulmón, aunque también se han observado en otros órganos, como la piel y los riñones. La infección por SARS-CoV-2 induce un estado protrombótico generalizado que se atribuye a una conjunción de factores como la hipoxia, el exceso de apoptosis celular y, sobre todo, una hiperactivación del sistema inmune. Entre las situaciones protrombóticas inmunomediadas destaca el síndrome antifosfolipídico, en el cual se observan eventos trombóticos de repetición en presencia de anticuerpos antifosfolipídicos (AAF). Existen numerosos estudios que reportan una elevada prevalencia de AAF en los pacientes con infección por la COVID-19; sin embargo, los resultados muestran discordancias en los datos de prevalencia de AAF y su rol en la patogenia sobre la trombosis en estos pacientes, lo que que podría deberse a la heterogeneidad de los procedimientos de detección de los AAF o a elevaciones transitorias de los niveles de AAF no patogénicos en el contexto de la infección. En esta revisión se busca aclarar el papel de los AAF en la infección por COVID-19, intentando responder a la pregunta de si se trata de una coagulopatía propia o es secundaria a un síndrome antifosfolipídico.

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.

Anti-phosphatidylserine/prothrombin antibodies in patients with polyarteritis nodosa.

INTRODUCTION: Anti-phospatidylserine/prothrombin (aPS/PT) antibodies have been described in cutaneous Polyarteritis Nodosa (PAN) in association with specific manifestations. OBJECTIVES: To determine aPS/PT antibodies in patients with PAN and its correlation with clinical manifestations. METHODS: Cross-sectional comparative study including PAN patients and 20 controls (10 Microscopic Polyangiitis [MPA] and 10 Behçet's disease [BD]). Clinical and demographic variables, treatment, serologic markers, prognosis, activity and damage indexes were evaluated. aPS/PT, anti-cardiolipin (aCL), anti-beta 2 glycoprotein 1 (anti-B2GP1) antibodies, and lupus anticoagulant (LA) were determined. RESULTS: Fourteen patients with PAN were included, 11 (79%) women, with disease duration of 207 months, and mostly inactive disease. Only one patient with PAN and one with BD were positive for aPS/PT IgG. LA was the most frequent antibody identified. One patient with MPA and one with BD were positive for aCL IgM; one with MPA for anti-B2GP1 IgG, and one with PAN for anti-B2GP1 IgM. CONCLUSIONS: aPS/PT antibodies are not frequent in patients with longstanding inactive PAN.

Anticuerpos antifosfatidilserina/protrombina en pacientes con poliarteritis nodosa / Anti-Phosphatidylserine/Prothrombin antibodies in patients with Polyarteritis Nodosa

Antecedentes: Anticuerpos antifosfatidilserina/protrombina (aPS/PT) han sido descritos en poliarteritis nodosa (PAN) cutánea, en asociación con manifestaciones específicas. Objetivos: Determinar anticuerpos aPS/PT en pacientes con PAN y analizar su correlación con manifestaciones clínicas. Métodos: Estudio transversal comparativo de pacientes con PAN y 20 controles (10 con poliangitis microscópica [PAM] y 10 con enfermedad de Behçet [EB]). Se evaluaron variables demográficas, clínicas, serológicas y tratamiento; índices de pronóstico, actividad y daño. Se determinaron anticuerpos aPS/PT, anticardiolipina (aCL), anti-beta 2 glicoproteína 1 (anti-B2GP1) y anticoagulante lúpico (AL). Resultados: Fueron incluidos 14 pacientes con PAN, 11 (79%) mujeres, con duración de la enfermedad de 207 meses, y principalmente enfermedad inactiva. Sólo un paciente con PAN y uno con EB fueron positivos para aPS/PT IgG. El anticuerpo antifosfolípido más frecuente fue AL. Un paciente con PAM y uno con EB fueron positivos para aCL IgM; uno con PAM para anti-B2GP1 IgG, uno con PAN para anti-B2GP1 IgM. Conclusiones: Los anticuerpos aPS/PT son infrecuentes en pacientes con PAN inactiva de larga evolución.(AU)

Introduction: Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies have been described in cutaneous Polyarteritis Nodosa (PAN) in association with specific manifestations. Objectives: To determine aPS/PT antibodies in patients with PAN and its correlation with clinical manifestations.Methods: Cross-sectional comparative study including PAN patients and 20 controls (10 Microscopic Polyangiitis [MPA] and 10 Behçet's disease [BD]). Clinical and demographic variables, treatment, serological markers, prognosis, activity and damage indexes were evaluated. aPS/PT, anti-cardiolipin (aCL), anti-beta 2 glycoprotein 1 (anti-B2GP1) antibodies, and lupus anticoagulant (LA) were determined. Results: Fourteen patients with PAN were included, 11 (79%) women, with disease duration of 207 months, and mostly inactive disease. Only one patient with PAN and one with BD were positive for aPS/PT IgG. LA was the most frequent antibody identified. One patient with MPA and one with BD were positive for aCL IgM; one with MPA for anti-B2GP1 IgG, and one with PAN for anti-B2GP1 IgM. Conclusions: aPS/PT antibodies are not frequent in patients with longstanding inactive PAN.(AU)

Retinal arterial and venous obstruction as the first manifestation of an antiphospholipid antibody syndrome.

CASE REPORT: A 34 year-old woman presented with decrease in visual acuity in her right eye (RE). Her past medical history was unremarkable. Dilated fundus examination revealed a central venous occlusion and an obstruction of the cilioretinal artery. Given the patient age, a cardiology and haematology screen was obtained to rule out hypercoagulation disorders and thromboembolic disease. Antiplatelet, anticoagulant, and corticosteroid therapy were started. The laboratory result was positive for anticardiolipin and antiphospholipid antibody. A diagnosis of antiphospholipid syndrome (APS) was made. DISCUSSION: Antiphospholipid syndrome may cause thrombosis in any organ. The involvement of the retinal vessels may be the first manifestation of this entity. This diagnosis is important to prevent recurrent thrombotic events.

Obstrucción arterial y venosa retiniana como primera manifestación de un síndrome de anticuerpos antifosfolípidos / Retinal arterial and venous obstruction as the first manifestation of an antiphospholipid antibody syndrome

Mujer de 34 años sin antecedentes de interés que acudió por disminución de visión del ojo derecho. El examen reveló una obstrucción de vena central de la retina y de la arteria ciliorretiniana. Dada la edad de la paciente se consultó con cardiología y hematología para descartar un estado de hipercoagulabilidad y patología tromboembólica. La analítica fue positiva para los anticuerpos anticardiolipina y antifosfolípidos. Se diagnosticó de un síndrome de anticuerpos antifosfolípidos. Se inició tratamiento antiagregante, anticoagulante y corticoideo. Discusión El síndrome antifosfolípido puede causar trombosis en cualquier órgano. La afectación de los vasos retinianos puede ser la primera manifestación. Su diagnóstico es importante para evitar fenómenos trombóticos recurrentes. (AU)

A 34 year-old woman presented with decrease in visual acuity in her right eye (RE). Her past medical history was unremarkable. Dilated fundus examination revealed a central venous occlusion and an obstruction of the cilioretinal artery. Given the patient age, a cardiology and haematology screen were obtained to rule out hypercoagulation disorders and thromboembolic disease. Antiplatelet, anticoagulant, and corticosteroid therapy were started. The laboratory result was positive for anticardiolipin and antiphospholipid antibody. A diagnosis of antiphospholipid syndrome (APS) was made. Discussion Antiphospholipid syndrome may cause thrombosis in any organ. The involvement of the retinal vessels may be the first manifestation of this entity. This diagnosis is important to prevent recurrent thrombotic events. (AU)

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.

Manifestaciones relacionadas con alteraciones en la coagulación en lupus eritematoso sistémico de inicio juvenil. Reporte de casos y revisión de la literatura / Manifestations related to alterations in coagulation in systemic lupus erythematosus of juvenile onset. Case report and literature review

RESUMEN Las alteraciones hematológicas son comunes en los pacientes con lupus eritematoso sistémico (LES). Pueden expresarse relacionadas con el compromiso de las líneas celulares y con la presencia de alteraciones de la coagulación. El compromiso en la coagulación se asocia con manifestaciones trombóticas. Se han descrito factores de riesgo asociados a trombosis, como la presencia de niveles elevados de homocisteína, déficit adquirido de la proteína S, proteína C y antitrombina. Sin embargo, la diátesis hemorrágica también se ha descrito con menor frecuencia y relacionada con el déficit de factores de la coagulación, secundaria a la presencia de inhibidores. Presentamos 3 pacientes con LES juvenil con manifestaciones hematológicas poco usuales y revisión de la literatura relacionada. Se concluye que las manifestaciones hematológicas en LES juvenil no solo se relacionan con alteraciones en las líneas celulares. Trombosis vasculares y trastornos hemorrágicos deben sospecharse. El diagnóstico precoz y el tratamiento temprano disminuyen la morbimortalidad relacionada con este tipo de manifestaciones.

ABSTRACT Haematological alterations are common in patients with systemic lupus erythematosus (SLE). These haematological manifestations may be expressed related to the involvement of cells affected and coagulation changes. The compromise in coagulation is associated with thrombotic manifestations. Risk factors associated with thrombosis have been described, such as the presence of elevated levels of homocysteine, acquired deficit of protein S, protein C, and antithrombin. However, the haemorrhagic diathesis has also been described at a lower frequency and related to the acquired deficiency of coagulation factors caused by the development of autoantibodies directed against coagulation factors. The cases are presented of 3 patients with juvenile SLE with unusual haematological manifestations, as well as a review of the literature in relation to them. The haematological manifestations in juvenile SLE are not only related to alterations in cell lines, vascular thrombosis and bleeding disorders should also be suspected. Early diagnosis and treatment reduces morbidity and mortality related to this type of manifestations.

Anti-Phosphatidylserine/Prothrombin antibodies in patients with Polyarteritis Nodosa. / Anticuerpos antifosfatidilserina/protrombina en pacientes con poliarteritis nodosa.

INTRODUCTION: Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies have been described in cutaneous Polyarteritis Nodosa (PAN) in association with specific manifestations. OBJECTIVES: To determine aPS/PT antibodies in patients with PAN and its correlation with clinical manifestations. METHODS: Cross-sectional comparative study including PAN patients and 20 controls (10 Microscopic Polyangiitis [MPA] and 10 Behçet's disease [BD]). Clinical and demographic variables, treatment, serological markers, prognosis, activity and damage indexes were evaluated. aPS/PT, anti-cardiolipin (aCL), anti-beta 2 glycoprotein 1 (anti-B2GP1) antibodies, and lupus anticoagulant (LA) were determined. RESULTS: Fourteen patients with PAN were included, 11 (79%) women, with disease duration of 207 months, and mostly inactive disease. Only one patient with PAN and one with BD were positive for aPS/PT IgG. LA was the most frequent antibody identified. One patient with MPA and one with BD were positive for aCL IgM; one with MPA for anti-B2GP1 IgG, and one with PAN for anti-B2GP1 IgM. CONCLUSIONS: aPS/PT antibodies are not frequent in patients with longstanding inactive PAN.

Recommendations of the Spanish Rheumatology Society for Primary Antiphospholipid Syndrome. Part I: Diagnosis, Evaluation and Treatment. / Recomendaciones de la Sociedad Española de Reumatología sobre síndrome antifosfolípido primario. Parte I: Diagnóstico, evaluación y tratamiento.

OBJECTIVE: The difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for primary antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS. METHODS: A panel of four rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for drafting the document, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network [SIGN] levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques). RESULTS: 46 recommendations were drawn up, addressing five main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the first 21, referring to the areas of: diagnosis, evaluation and treatment of primary APS. The document provides a table of recommendations and treatment algorithms. CONCLUSIONS: An update of the SER recommendations on APS is presented. This document corresponds to partI, related to diagnosis, evaluation and treatment. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A partII has also been prepared, which addresses aspects related to obstetric SAF and special situations.

Recommendations of the Spanish Rheumatology Society for Primary Antiphospholipid Syndrome. Part II: Obstetric Antiphospholipid Syndrome and Special Situations. / Recomendaciones de la Sociedad Española de Reumatología sobre síndrome antifosfolípido primario. Parte II: síndrome antifosfolípido obstétrico y situaciones especiales.

OBJECTIVE: The difficulty in diagnosis and the spectrum of clinical manifestations that can determine the choice of treatment for antiphospholipid syndrome (APS) has fostered the development of recommendations by the Spanish Society of Rheumatology (SER), based on the best possible evidence. These recommendations can serve as a reference for rheumatologists and other specialists involved in the management of APS. METHODS: A panel of 4rheumatologists, a gynaecologist and a haematologist with expertise in APS was created, previously selected by the SER through an open call or based on professional merits. The stages of the work were: identification of the key areas for the document elaboration, analysis and synthesis of the scientific evidence (using the Scottish Intercollegiate Guidelines Network, SIGN levels of evidence) and formulation of recommendations based on this evidence and formal assessment or reasoned judgement techniques (consensus techniques). RESULTS: Forty-six recommendations were drawn up, addressing 5main areas: diagnosis and evaluation, measurement of primary thromboprophylaxis, treatment for APS or secondary thromboprophylaxis, treatment for obstetric APS and special situations. These recommendations also include the role of novel oral anticoagulants, the problem of recurrences or the key risk factors identified in these subjects. This document reflects the last 25, referring to the areas of: obstetric APS and special situations. The document provides a table of recommendations and treatment algorithms. CONCLUSIONS: Update of SER recommendations on APS is presented. This document corresponds to part II, related to obstetric SAF and special situations. These recommendations are considered tools for decision-making for clinicians, taking into consideration both the decision of the physician experienced in APS and the patient. A part I has also been prepared, which addresses aspects related to diagnosis, evaluation and treatment.

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.

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)

Diagnóstico de laboratorio de anticuerpos antifosfolípidos / 2016 / Laboratory diagnosis of the antiphospholipid antibodies / 2016 / Diagnóstico laboratorial de anticorpos antifosfolípides / 2016

Los anticuerpos antifosfolípidos (aFL) en pacientes con historia de complicaciones clínicas trombóticas tanto en territorio venoso como arterial y/o con morbilidad obstétrica definen al síndrome antifosfolípido (SAF). Los aFL en el plasma de pacientes pueden ser detectados como actividad de inhibidor lúpico (IL) a través de la prolongación de pruebas de coagulación dependientes de fosfolípidos o a través de ensayos en fase sólida como los ELISAs para anticuerpos anticardiolipina (aCL) o anti-b2 glicoproteína I (ab2GPI). Para el diagnóstico de SAF se requiere que los aFL sean demostrados en al menos 2 oportunidades con un período no menor a 12 semanas entre ambas evaluaciones de laboratorio. Los aCL y/o ab2GPI de isotipo IgG y/o IgM deben estar presentes en títulos moderados o altos. En los últimos años se han publicado varias recomendaciones para la evaluación del IL y también de los aFL por métodos inmunológicos. En este artículo se mencionan las guías internacionales que existen al respecto para un diagnóstico correcto de los aFL en el laboratorio.

Antiphospholipid antibodies (aPL) in patients with a history of thrombotic clinical complications in both venous and arterial territory and/ or obstetric morbidity define the antiphospholipid syndrome (APS). aPL in patients’ plasma can be detected as lupus anticoagulant (LA) activity through the prolongation of phospholipid-dependent clotting tests or through solid-phase assays such as ELISAs for anti-cardiolipin antibodies (aCL) or anti-b2 glycoprotein I(ab2GPI).Diagnosis of APS requires that aPL are demonstrated in at least 2 opportunities with no less than 12 weeks between two laboratory evaluations. aCL and ab2GPIof IgG and/ or IgM isotypes must be present at moderate or high titers. In recent years,there have been several recommendations for the evaluation of LA and also aPL by immunological methods. This article describes the international guidelines available for a correct diagnosis of aPL in the laboratory.

Anticorpos antifosfolípides (aPL) em pacientes com história de complicações clínicas trombóticas em ambos os territórios venoso e arterial e/ou com morbidade obstétrica, definem a síndrome antifosfolípide (APS). Os aPL no plasma de pacientes pode ser detectado como atividade de inibidor lúpico (IL) por meio do prolongamento de testes de coagulação dependentes de fosfolipídeos, ou por meio de ensaios em fase sólida, tais como ensaios ELISA para anticorpos anticardiolipina (aCL) ou anti-b2 glicoproteína I (ab2GPI). Para o diagnóstico de APS requer que os aPL sejam demonstrados em pelo menos 2 oportunidades com um período de não menos de 12 semanas entre ambas as avaliações laboratoriais. aCL e/ou ab2GPI de isotipo IgG e/ou IgM têm de estar presentes em títulos moderados ou elevados. Nos últimos anos foram publicadas várias recomendações para a avaliação do IL e também dos aPL por métodos imunológicos. Este artigo menciona os guias internacionais que existem a esse respeito para um diagnóstico certo dos aPL no laboratório.

Clinical practice guidelines for the management of pregnancy in women with autoimmune rheumatic diseases of the Mexican College of Rheumatology. Part II.

BACKGROUND: Pregnancy in women with autoimmune rheumatic diseases is associated with several maternal and fetal complications. The development of clinical practice guidelines with the best available scientific evidence may help standardize the care of these patients. OBJECTIVES: To provide recommendations regarding prenatal care, treatment, and a more effective monitoring of pregnancy in women with lupus erythematosus, rheumatoid arthritis (RA) and antiphospholipid syndrome (APS). METHODOLOGY: Nominal panels were formed for consensus, systematic search of information, development of clinical questions, processing and staging of recommendations, internal validation by peers and external validation of the final document. The quality criteria of the AGREE II instrument were followed. RESULTS: The panels answered 37 questions related to maternal and fetal care in lupus erythematosus, RA and APS, as well as for use of antirheumatic drugs during pregnancy and lactation. The recommendations were discussed and integrated into a final manuscript. Finally, the corresponding algorithms were developed. In this second part, the recommendations for pregnant women with RA, APS and the use of antirheumatic drugs during pregnancy and lactation are presented. CONCLUSIONS: We believe that the Mexican clinical practice guidelines for the management of pregnancy in women with RA and APS integrate the best available evidence for the treatment and follow-up of patients with these conditions.

Aborto Recurrente de Etiología Autoinmune / Autoimmune Recurrent Abortion

El curso normal del embarazo implica una serie de cambios inmunológicos que permiten el desarrollo armónico fetal. En mujeres con pérdida recurrente de la gestación, diversas etiologías se han relacionado como desencadenantes de dichas pérdidas; jugando el factor autoinmune un papel cada vez más importante. En el presente artículo, a partir de una búsqueda sistemática de información, se exponen en detalle los aspectos inmunológicos del embarazo normal, así como las alteraciones que a este nivel se presentan en mujeres con aborto recurrente. Además, se realiza una orientación diagnóstica y se exponen las diversas opciones terapéuticas utilizadas, haciendo énfasis en la necesidad de establecer protocolos estandarizados para el manejo de esta entidad.

Normal development of the pregnancy involves a number of immunological changes that allow harmonic fetal development. In women with recurrent pregnancy loss several etiologies have been implicated as triggers of such losses; autoimmune factor is nowadays playing an increasingly more important roll. In this article, based on a systematic search of information, are exposed in details the immunological aspects of normal pregnancy, as well as the immune alterations that occur in women with recurrent abortion. In addition, a diagnostic guidance is made and the various therapeutic options used are pointed out, emphasizing the need to establish standardized protocols for the management of this entity.

Síndrome antifosfolipídico y afectación cardiovascular / Antiphospholipid syndrome and cardiovascular affectation / Síndrome do anticorpo antifosfolipídeo e comprometimento cardiovascular

El síndrome antifosfolípido se define como la presencia de trombosis arteriales o venosas recurrentes, pérdidas repetidas de embarazo y trombocitopenia en presencia de anticuerpos a cardiolipina o anticoagulante lúpico. Se realizo esta revisión con el fin de determinar si este síndrome debe ser considerado actualmente un factor de riesgo cardiovascular. Se presenta en mujeres jóvenes por lo cual al ser diagnosticado nos obliga a realizar un control exhaustivo y debe tener un abordaje multidisciplinario. Dentro de las manifestaciones cardiovasculares el paciente puede presentar infarto agudo de miocardio, endocarditis pseudo-infecciosa, afectación valvular e hipertensión pulmonar.

Antiphospholipid syndrome is defined as the presence of recurrent arterial or venous thrombosis, repeated pregnancy loss and thrombocytopenia in the presence of antibodies to cardiolipin or lupus anticoagulant. This review was performed in order to determine whether this syndrome should now be considered a cardiovascular risk factor. It occurs in young women, therefore, to be diagnosed forces us to make a thorough control and should have a multidisciplinary approach. Among the cardiovascular manifestations the patient may develop acute myocardial infarction, pseudo-infectious endocarditis, valve disease and pulmonary hypertension.

A síndrome do anticorpo antifosfolipídeo é definida como a presença de trombose arterial ou venosa recorrente, repetidos abortos e trombocitopenia na presença de anticorpos anti-cardiolipina ou lúpus anticoagulante. Esta avaliação foi realizada, a fim de determinar se esta síndrome deve agora ser considerada um fator de risco cardiovascular. Ela ocorre em mulheres jovens, por isso, de ser diagnosticada nos obriga a fazer um estudo aprofundado e deve ter uma abordagem multidisciplinar. Entre as manifestações cardiovasculares, o paciente pode desenvolver infarto agudo do miocárdio, endocardite pseudo-infecciosa, valvopatia e hipertensão pulmonar.