RESUMO
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.
Assuntos
Síndrome Antifosfolipídica , Anticorpos Anticardiolipina , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica/diagnóstico , Humanos , Protrombina , Sensibilidade e Especificidade , beta 2-Glicoproteína IRESUMO
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.
Assuntos
Humanos , Síndrome Antifosfolipídica/diagnóstico , Protrombina , Sensibilidade e Especificidade , Anticorpos Antifosfolipídeos , Anticorpos Anticardiolipina , beta 2-Glicoproteína IRESUMO
BACKGROUND: The term Direct Oral Anticoagulants (DOACs) refers to a group of drugs that inhibit factor Xa or thrombin. Even though their use for treating different thrombotic or prothrombotic conditions is increasing recently, there is no compelling evidence indicating that those medications are safe in all antiphospholipid syndrome (APS) patients. METHODOLOGY: To address this issue, specialists from the Antiphospholipid Syndrome Committee of the Brazilian Society of Rheumatology performed a comprehensive review of the literature regarding DOACs use in APS to answer the three following questions: (1) potential mechanisms of action of these drugs that could be relevant to APS pathogenesis, (2) DOACs interference on lupus anticoagulant testing, and (3) the efficacy of DOACs in APS. POSITION STATEMENT: After critically reviewing the relevant evidence, the authors formulated 8 Position Statements about DOACs use in APS. CONCLUSION: DOACs should not be routinely used in APS patients, especially in those with a high-risk profile (triple positivity to aPL, arterial thrombosis, and recurrent thrombotic events). In addition, DOACs interferes with LA testing, leading to false-positive results in patients investigating APS.
Assuntos
Comitês Consultivos , Síndrome Antifosfolipídica/tratamento farmacológico , Antitrombinas/uso terapêutico , Consenso , Administração Oral , Antitrombinas/efeitos adversos , Antitrombinas/farmacologia , Brasil , Contraindicações de Medicamentos , Interações Medicamentosas , Substituição de Medicamentos , Humanos , Inibidor de Coagulação do Lúpus/análise , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Reumatologia , Sociedades Médicas , Trombose/tratamento farmacológico , Resultado do TratamentoRESUMO
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.
Assuntos
Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Diagnóstico DiferencialRESUMO
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
Assuntos
Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/fisiopatologia , Autoimunidade/imunologia , Trombose/diagnóstico , Trombose/terapia , Anticorpos Anticardiolipina , Anticoagulantes/uso terapêutico , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/fisiopatologia , Hemorragia/complicações , Heparina/uso terapêutico , Inibidor de Coagulação do Lúpus , Fatores de RiscoRESUMO
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.
Assuntos
Síndrome Antifosfolipídica , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/terapia , Diagnóstico Diferencial , HumanosRESUMO
Systemic lupus erythematosus (SLE) is a chronic multisystemic autoimmune disease driven by genetic, hormonal, and environmental factors. Despite the advances in diagnostic and therapeutic approaches in the last decades, SLE still leads to significant morbidity and increased mortality. Although a cure for SLE is still unknown, treatment is required to control acute disease exacerbation episodes (flares), decrease the frequency and severity of subsequent lupus flares, address comorbidities, and prevent end-organ damage. While conventional SLE pharmacotherapy may exhibit suboptimal efficacy and substantial toxicity, a growing knowledge of the disease pathogenesis enabled the research on novel therapeutic agents directed at specific disease-related targets. In this paper, we review the recent progress in the clinical investigation of biologic agents targeting B cells, T cells, cytokines, innate immunity, and other immunologic or inflammatory pathways. Although many investigational agents exhibited insufficient efficacy or inadequate safety in clinical trials, one of them, belimumab, fulfilled the efficacy and safety regulatory requirements and was approved for the treatment of SLE in Europe and the USA, which confirms that, despite all difficulties, advances in this field are possible.
Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Produtos Biológicos/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , HumanosRESUMO
The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis, gestational morbidity and presence of elevated and persistently positive serum titers of antiphospholipid antibodies. The treatment of APS is still controversial, because any therapeutic decision potentially faces the risk of an insufficient or excessive antithrombotic coverage associated with anticoagulation and its major adverse effects. This guideline was elaborated from nine relevant clinical questions related to the treatment of APS by the Committee of Vasculopathies of the Brazilian Society of Rheumatology. Thus, this study aimed at establishing a guideline that included the most relevant and controversial questions in APS treatment, based on the best scientific evidence available. The questions were structured by use of the PICO (patient, intervention or indicator, comparison and outcome) process, enabling the generation of search strategies for evidence in the major primary scientific databases (MEDLINE/PubMed, Embase, Lilacs, Scielo, Cochrane Library, Premedline via OVID). A manual search for evidence and theses was also conducted (BDTD and IBICT). The evidence retrieved was selected based on critical assessment by using discriminatory instruments (scores) according to the category of the therapeutic question (JADAD scale for randomized clinical trials and Newcastle-Ottawa scale for non-randomized studies). After defining the potential studies to support the recommendations, they were selected according to level of evidence and grade of recommendation, according to the Oxford classification.
Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Anticoagulantes/uso terapêutico , HumanosRESUMO
A síndrome do anticorpo antifosfolipídeo (SAF) é uma doença sistêmica autoimune caracterizada por trombose arterial e venosa, morbidade gestacional e presença de níveis séricos de anticorpos antifosfolipídeos elevados e persistentemente positivos. O tratamento da SAF ainda é sujeito a controvérsias, já que qualquer decisão terapêutica potencialmente irá confrontar-se com o risco de uma cobertura antitrombótica insuficiente ou com o risco excessivo associado à anticoagulação e seus principais efeitos adversos. Esta diretriz foi elaborada a partir de nove questões clínicas relevantes e relacionadas ao tratamento da SAF pela Comissão de Vasculopatias da Sociedade Brasileira de Reumatologia. O objetivo deste trabalho foi criar uma diretriz que incluísse as questões mais relevantes e controversas no tratamento da SAF, com base na melhor evidência científica disponível. As questões foram estruturadas por meio do P.I.C.O. (paciente, intervenção ou indicador, comparação e outcome/desfecho), o que possibilitou a geração de estratégias de busca da evidência nas principais bases primárias de informação científica (MEDLINE/Pubmed, Embase, Lilacs/Scielo, Cochrane Library, Premedline via OVID). Também realizou-se busca manual da evidência e de teses (BDTD e IBICT). A evidência recuperada foi selecionada a partir da avaliação crítica, utilizando instrumentos (escores) discriminatórios de acordo com a categoria da questão terapêutica (JADAD para ensaios clínicos randomizados e New Castle Ottawa Scale para estudos não randomizados). Após definir os estudos potenciais para sustento das recomendações, eles foram selecionados pela força da evidência e pelo grau de recomendação, segundo a classificação de Oxford.
The antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis, gestational morbidity and presence of elevated and persistently positive serum titers of antiphospholipid antibodies. The treatment of APS is still controversial, because any therapeutic decision potentially faces the risk of an insufficient or excessive antithrombotic coverage associated with anticoagulation and its major adverse effects. This guideline was elaborated from nine relevant clinical questions related to the treatment of APS by the Committee of Vasculopathies of the Brazilian Society of Rheumatology. Thus, this study aimed at establishing a guideline that included the most relevant and controversial questions in APS treatment, based on the best scientific evidence available. The questions were structured by use of the PICO (patient, intervention or indicator, comparison and outcome) process, enabling the generation of search strategies for evidence in the major primary scientific databases (MEDLINE/PubMed, Embase, Lilacs, Scielo, Cochrane Library, Premedline via OVID). A manual search for evidence and theses was also conducted (BDTD and IBICT). The evidence retrieved was selected based on critical assessment by using discriminatory instruments (scores) according to the category of the therapeutic question (JADAD scale for randomized clinical trials and Newcastle-Ottawa scale for non-randomized studies). After defining the potential studies to support the recommendations, they were selected according to level of evidence and grade of recommendation, according to the Oxford classification.