Primary, secondary, and catastrophic antiphospholipid syndrome: what's in a name?

The association of the lupus anticoagulant with thrombosis and recurrent pregnancy loss was first recognized over a 20-year period between the early 1960s and early 1980s. The introduction of the anticardiolipin test in 1983 and the recognition of its association with clinical features similar to the lupus anticoagulant led to an exponential growth of interest in this disorder. The belief that anticardiolipin antibodies and lupus anticoagulant belonged to the family of antiphospholipid antibodies led to the disorder being named the antiphospholipid syndrome (APS). Efforts by individual investigators to introduce criteria for classification of APS and to standardize anticardiolipin antibody and lupus anticoagulant tests were started in the mid-1980s to ensure more reliable recognition and treatment of affected patients. Another layer of complexity was introduced with recognition that many anticardiolipin antibody-positive sera also bound the antigen beta (2) glycoprotein I. With increasingly sophisticated epidemiologic and prospective studies in the 1990s, more structured and better-documented criteria for APS were introduced in 1999 and modified in 2006. These criteria have been widely adopted. Whereas data supporting subclassification of APS into primary and secondary subgroups remain tenuous, a small percentage of patients do appear subject to clinical features termed the catastrophic antiphospholipid syndrome. Introduction of classification criteria for APS has enabled more reliable prospective studies, the promise of better management, and more valid tests for recognition of the disorder.

Síndrome antifosfolípido: mecanismos patogénicos, diagnóstico y tratamiento / Antiphospholipid syndrome: pathogenic mechanisms, diagnosis and treatment

Los anticuerpos antifosfolípidos están asociados con trombosis y pérdidas fetales en pacientes con síndrome antifosfolípido. Se han descrito diversos mecanismos patogénicos para explicar las manifestaciones clínicas producidas por los anticuerpos. En esta revisión se discuten las modalidades corrientes para el tratamiento y se describe en detalle una actualización de las pruebas de laboratorio utilizadas para confirmar el diagnóstico de síndrome antifosfolípido. La prueba de anticuerpos anticardiolipina ha sido utilizada ampliamente por los médicos desde la mitad de los años 80 para el diagnóstico de pacientes con síndrome antifosfolípido. Establecer correctamente un diagnóstico permite manejar efectivamente pacientes con trombosis recurrentes y pérdidas fetales. La prueba de anticuerpos anticardiolipina fue establecida en 1983 como una técnica de radioinmunoensayo y fue luego convertida en un enzimoinmunoensayo (ELISA). Otra prueba utilizada comunmente en el diagnóstico de síndrome antifosfolípido es el anticoagulante lúpico. La prueba de anticuerpos anticardiolipina por ELISA essensible para el diagnóstico de síndrome antifosfolípido pero de baja especificidad. Por otra parte, la prueba de anticoagulante lúpico, no obstante ser más específica, no es tan sensible como la prueba de anticuerpos anticardiolipina por ELISA. Se han desarrollado otras pruebas más específicas como la determinación de anticuerpos anti-ß2 glicoproteína I (anti-ß2GPI), antiprotrombina (anti-PT) y la prueba APhL por ELISA, que utiliza fosfolípidos cargados negativamente en lugar de cardiolipina como antígeno para cubrir los platos de microtitulación. Este módulo trata en detalle el valor clínico de las pruebas antes mencionadas, los problemas técnicos asociados con ellas, los criterios utilizados por el laboratorio para el diagnóstico de síndrome antifosfolípido y las posibles nuevas y mejores pruebas que estarán disponibles en un futuro cercano para el diagnóstico de síndrome antifosfolípido.

Mechanisms of aPL-mediated thrombosis: effects of aPL on endothelium and platelets.

Antiphospholipid antibodies (aPL) are associated with thrombosis and pregnancy loss in patients with systemic lupus erythematosus and antiphospholipid syndrome. Strong evidence demonstrates that aPL are pathogenic in vivo from studies that utilized animal models of thrombosis, endothelial cell activation, and pregnancy loss. However, the mechanisms by which aPL mediate disease are only partially understood, and our knowledge is limited by the polyspecificity of the antibodies, the multiple potential end-organ targets, and the variability of the clinical context in which the disease may present. This review discusses and summarizes the most current data available on molecular interactions and pathogenic mechanisms in antiphospholipid syndrome.

Baja prevalencia de anticuerpos antifosfolípidos autoinmunes en enfermedades hepáticas / Low prevalence of autoimmune antiphospholipid antibodies in hepatic diseases

Antiphospholipid antibodies (aPL) have been associated with different diseases. They are defined as a large family of immunoglobulins (Ig) of either alloantibodies or autoantibodies. The autoimmune antibodies are associated with venous and/or arterial thrombosis, thrombocytopenia and recurrent fetal loss in the so-called antiphospholipid syndrome or in systemic lupus erythematosus. These antibodies are directed against proteins or phospholipid-protein complexes. On the contrary, antiphospholipid antibodies (alloantibodies) which are found in infectious diseases sera (syphilis, HIV, and other viral diseases), disappear with illness remission and are directed to phospholipids alone (particularly cardiolipin) and are not associated with thrombosis or recurrent fetal loss. However, the role and type of aPL found during hepatic diseases is still unclear. To investigate the prevalence of autoimmune aPL (IgG and IgM) during different hepatic diseases, we have studied 128 patients with hepatitis C virus, hepatitis B virus and hepatic autoimmune diseases without treatment as well as 40 healthy control subjects. We have used a specific ELISA kit, that uses a mixture of phospholipid instead of cardiolipin alone, and allows a better detection of aPL of the autoimmune type. Our results show that autoimmune aPL are not significantly increased in viral hepatic diseases (2%) or autoimmune diseases of the liver (3%) when compared to the control group (0%). (AU)

Baja prevalencia de anticuerpos antifosfolípidos autoinmunes en enfermedades hepáticas / Low prevalence of autoimmune antiphospholipid antibodies in hepatic diseases

Antiphospholipid antibodies (aPL) have been associated with different diseases. They are defined as a large family of immunoglobulins (Ig) of either alloantibodies or autoantibodies. The autoimmune antibodies are associated with venous and/or arterial thrombosis, thrombocytopenia and recurrent fetal loss in the so-called antiphospholipid syndrome or in systemic lupus erythematosus. These antibodies are directed against proteins or phospholipid-protein complexes. On the contrary, antiphospholipid antibodies (alloantibodies) which are found in infectious diseases sera (syphilis, HIV, and other viral diseases), disappear with illness remission and are directed to phospholipids alone (particularly cardiolipin) and are not associated with thrombosis or recurrent fetal loss. However, the role and type of aPL found during hepatic diseases is still unclear. To investigate the prevalence of autoimmune aPL (IgG and IgM) during different hepatic diseases, we have studied 128 patients with hepatitis C virus, hepatitis B virus and hepatic autoimmune diseases without treatment as well as 40 healthy control subjects. We have used a specific ELISA kit, that uses a mixture of phospholipid instead of cardiolipin alone, and allows a better detection of aPL of the autoimmune type. Our results show that autoimmune aPL are not significantly increased in viral hepatic diseases (2%) or autoimmune diseases of the liver (3%) when compared to the control group (0%).