Non-criteria Antiphospholipid Antibodies: a narrative review.

The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these "criteria" of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the ß2 glycoprotein antibodies.

Non-criteria Antiphospholipid Antibodies: a narrative review

SUMMARY The 2006 Revised Sapporo Classification Criteria for Definite Antiphospholipid Syndrome included as laboratory criteria the tests for antiphospholipid antibodies whose accuracy was regarded as satisfactory according to the evidence available at that time. In practice, however, the sensitivity and specificity of these "criteria" of antiphospholipid antibodies are sometimes insufficient for identifying or ruling out antiphospholipid syndrome. It has been studied whether the accuracy of the laboratory diagnosis of the syndrome could be improved by testing for non-criteria antiphospholipid antibodies. In this work, we review evidence on the clinical associations and diagnostic value of the most commonly studied non-criteria antibodies, namely: antiphosphatidylethanolamine, anti-annexin A5, anti-prothrombin, anti-phosphatidylserine/prothrombin complex, IgA anticardiolipin, and IgG anti-domain I of the β2 glycoprotein antibodies.

RESUMO A classificação de Sapporo revisada para a síndrome antifosfolipídica definida de 2006 incluiu como critérios laboratoriais aqueles testes para anticorpos antifosfolípides cuja acurácia era considerada satisfatória de acordo com a evidência então disponível. Porém, na prática, a sensibilidade e especificidade desses anticorpos antifosfolípides "critério" são por vezes insuficientes para identificar ou descartar a síndrome antifosfolípide. Tem-se estudado se a acurácia do diagnóstico laboratorial da síndrome poderia ser melhorada por meio da testagem de anticorpos antifosfolípides não critério. Neste trabalho revisamos a evidência a respeito das associações clínicas e valor diagnóstico dos anticorpos não critério mais estudados, nomeadamente: anticorpos antifosfatidiletanolamina, antianexina A5, antiprotrombina, anticomplexo fosfatidilserina/protrombina, IgA anticardiolipina e IgG antidomínio I da anti-β2 glicoproteína I.

Omega-3 Fatty Acid Supplementation Improves Endothelial Function in Primary Antiphospholipid Syndrome: A Small-Scale Randomized Double-Blind Placebo-Controlled Trial.

Endothelial cells are thought to play a central role in the pathogenesis of antiphospholipid syndrome (APS). Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation has been shown to improve endothelial function in a number of diseases; thus, it could be of high clinical relevance in APS. The aim of this study was to evaluate the efficacy of n-3 PUFA supplementation on endothelial function (primary outcome) of patients with primary APS (PAPS). A 16-week randomized clinical trial was conducted with 22 adult women with PAPS. Patients were randomly assigned (1:1) to receive placebo (PL, n = 11) or n-3 PUFA (ω-3, n = 11) supplementation. Before (pre) and after (post) 16 weeks of the intervention, patients were assessed for endothelial function (peripheral artery tonometry) (primary outcome). Patients were also assessed for systemic markers of endothelial cell activation, inflammatory markers, dietary intake, international normalized ratio (INR), and adverse effects. At post, ω-3 group presented significant increases in endothelial function estimates reactive hyperemia index (RHI) and logarithmic transformation of RHI (LnRHI) when compared with PL (+13 vs. -12%, p = 0.06, ES = 0.9; and +23 vs. -22%, p = 0.02, ES = 1.0). No changes were observed for e-selectin, vascular adhesion molecule-1, and fibrinogen levels (p > 0.05). In addition, ω-3 group showed decreased circulating levels of interleukin-10 (-4 vs. +45%, p = 0.04, ES = -0.9) and tumor necrosis factor (-13 vs. +0.3%, p = 0.04, ES = -0.95) and a tendency toward a lower intercellular adhesion molecule-1 response (+3 vs. +48%, p = 0.1, ES = -0.7) at post when compared with PL. No changes in dietary intake, INR, or self-reported adverse effects were observed. In conclusion, 16 weeks of n-3 PUFA supplementation improved endothelial function in patients with well-controlled PAPS. These results support a role of n-3 PUFA supplementation as an adjuvant therapy in APS. Registered at http://ClinicalTrials.gov as NCT01956188.

Update on antiphospholipid antibody syndrome / Atualização da síndrome do anticorpo antifosfolípide

Summary Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.

Resumo A síndrome antifosfolipídide (APS) é uma doença autoimune caracterizada por tromboses e morbidade gestacional associadas à positividade de antiphospholipid antibodies (aPL). A maioria das manifestações da APS está diretamente relacionada aos eventos trombóticos, que podem afetar pequenos, médios ou grandes vasos. Outras manifestações como trombocitopenia, nefropatia, valvulopatia, disfunção cognitiva e úlceras cutâneas (chamadas de manifestações não critérios) agregam significativa morbidade e muitas vezes são refratárias ao tratamento convencional. Embora tenha sido inicialmente descrita em pacientes com lúpus eritematoso sistêmico (LES), a síndrome antifosfolípide também pode ocorrer em pacientes sem outras doenças autoimunes associadas. Apesar do caráter autoimune dessa síndrome, o tratamento da APS ainda é baseado na anticoagulação e na antiagregação plaquetária.

A importância de reconhecer a síndrome antifosfolípide na medicina vascular / The importance of recognizing antiphospholipid syndrome in vascular medicine

A síndrome antifosfolipíde (SAF) é uma doença autoimune sistêmica caracterizada por trombose arterial ou venosa recorrente e/ou morbidade gestacional e pela presença dos anticorpos antifosfolipídeos, podendo apresentar outras manifestações vasculares, como microangiopatia, arteriopatia crônica e SAF catastrófica. Determinados testes laboratoriais para a síndrome (por exemplo, o anticoagulante lúpico) podem sofrer interferência do uso de medicações anticoagulantes, dificultando o diagnóstico. A fisiopatologia da SAF é complexa, sendo enumerados no texto diversos mecanismos patogênicos relacionados à coagulação, ao endotélio e às plaquetas. Por fim, discutimos o tratamento da SAF de acordo com a presença e o tipo de manifestações clínicas, o uso dos anticoagulantes orais diretos e o manejo perioperatório de pacientes com SAF

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by recurrent arterial or venous thrombosis and/or gestational morbidity and by the presence of antiphospholipid antibodies. It can also cause other vascular manifestations such as microangiopathy, chronic arteriopathy and catastrophic APS (CAPS). Certain laboratory tests for the syndrome (for example, the lupus anticoagulant test) can be affected by the use of anticoagulant agents, making diagnosis more difficult. The pathophysiology of APS is complex, and several mechanisms of pathogenesis related to coagulation, endothelium, and platelets are discussed in this article. We conclude by discussing treatment of APS according to the presence and type of clinical manifestations, use of direct oral anticoagulants (DOAs), and perioperative management of patients with APS

Update on antiphospholipid antibody syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.

Avaliação não-invasiva das propriedades da parede arterial em pacientes com síndrome antifosfolípide primária / Non-invasive evaluation of arterial wall properties in patients with primary antiphospholipid syndrome

Objetivo: Avaliar de forma não-invasiva a rigidez arterial, parâmetro indireto de avaliação precoce de aterosclerose, nas pacientes através dos seguintes métodos: Velocidade de Onda de Pulso (VOP) e o Echo-tracking (ET). Pacientes e Métodos: 27 pacientes do sexo feminino com SAFP e 27 controles pareadas por sexo e idade foram selecionadas. As pacientes foram subdivididas de acordo com o sítio vascular: arterial (n=12) e venoso (n=11). Resultados: A VOP foi maior em pacientes com eventos arteriais, não foram observadas alterações em relação aos parâmetros do ET...

Objective: Evaluate the arterial stiffness, a surrogate marker of precocious atherosclerosis, using non-invasive methods: Pulse Wave Velocity (PWV) and the Echo-Tracking (ET) device, in PAPS patients. PATIENTS AND METHODS: 27 female patients with PAPS and 27 age- and sex-matched controls were consecutively selected. PAPS patients were subdivided according to the type of vascular exclusive event: arterial (n=12) and venous (n=11). RESULTS: The PWV was higher in PAPS patients with arterial events, we did not observe any abnormalities regarding ET parameters...

Avaliação não-invasiva das propriedades da parede arterial em pacientes com síndrome antifosfolípide primária / Non-invasive evaluation of arterial wall properties in patients with Primary Antiphospholipid Syndrome

Objetivo: Avaliar de forma não-invasiva a rigidez arterial, parâmetro indireto de avaliação precoce de aterosclerose, nas pacientes através dos seguintes métodos: Velocidade de Onda de Pulso (VOP) e o Echo-tracking (ET). Pacientes e Métodos: 27 pacientes do sexo feminino com SAFP e 27 controles pareadas por sexo e idade foram selecionadas. As pacientes foram subdivididas de acordo com o sítio vascular: arterial (n=12) e venoso (n=11). Resultados: A VOP foi maior em pacientes com eventos arteriais, não foram observadas alterações em relação aos parâmetros do ET...

Objective: Evaluate the arterial stiffness, a surrogate marker of precocious atherosclerosis, using non-invasive methods: Pulse Wave Velocity (PWV) and the Echo-Tracking (ET) device, in PAPS patients. PATIENTS AND METHODS: 27 female patients with PAPS and 27 age- and sex-matched controls were consecutively selected. PAPS patients were subdivided according to the type of vascular exclusive event: arterial (n=12) and venous (n=11). RESULTS: The PWV was higher in PAPS patients with arterial events, we did not observe any abnormalities regarding ET parameters...

Síndrome de Sjõgren primária com vasculite cutânea manifestada por úlceras em membro inferior / Primary Sjõgren's syndrome with cutaneous vasculitis manifested as leg ulcerations

A síndrome de Sjõgren (SS) primária é uma doença autoimune cujo espectro de manifestação clínica estende-se desde um acometimento órgão-específico (exocrinopatia auto-imune) até um processo sistêmico. O envolvimento da pele é bastante comum, e a freqüência de doença vascular inflamatória é estimada entre 20 por cento e 30 por cento. Duas formas clínicas específicas de vasculite cutânea, a púrpura palpável e urticária crônica são predominantes, mas eritema multiforme, eritema perstans, eritema nodoso, mácula eritematosa e nódulo subcutâneo também já foram descritos. Os autores descrevem o caso de uma paciente de 46 anos, que desenvolveu quadro de síndrome de Sjõgren primária, com manifestações oculares, orais, articulares e alterações laboratoriais (FAN, anti-Ro, fator reumatóide positivos, e hipergamaglobulinemia). Após dez anos do diagnóstico, apresentou úlcera em membro inferior, cuja biópsia confirmou tratar-se de lesão tipo vasculítica, com excelente resposta ao tratamento com ciclofosmida endovenosa. Foram descritos na literatura apenas dois relatos de caso de pacientes com úlceras em membros inferiores, como acometimento cutâneo da SS. Os autores ressaltam a importância do diferencial de úlceras em membros inferiores como acometimento cutâneo da SS primária.

[Primary Sjögren's syndrome with cutaneous vasculitis manifested as leg ulcerations]. / Síndrome de Sjögren primária com vasculite cutânea manifestada por úlceras em membro inferior.

Primary Sjögren's Syndrome (pSS) is an autoimmune disease with a large spectrum of clinical manifestations extending from an organ-specific involvement to a systemic process. The skin is affected quite commonly and the estimated frequency of inflammatory vascular lesions is from 20% to 30%. Two specific, clinically recognizable forms of cutaneous vasculitis predominate, palpable purpura and chronic urticaria, but erythema multiforme, erythema perstans, erythema nodosum, erithematous macules and subcutaneous nodules have also been described. The authors report the case of a 46-year-old female patient, diagnosed as primary SS, who presented ocular and oral symptoms, poliarthritis and laboratory alterations (with a positive ANA, anti-SSA, rheumatoid factor, and hypergammaglobulinemia). Ten years after the diagnosis, she presented leg ulcers. The biopsy confirmed the presence of vasculitic process, and the ulcers improved rapidly after the treatment with endovenous cyclophosphamide. There are only two reports of chronic ulceration of the legs as cutaneous manifestation of SS. The authors stress the importance of considering ulcers in the differential diagnosis of cutaneous involvement of primary SS.