ReviewThe relevance of “non-criteria” clinical manifestations of antiphospholipid syndrome: 14th International Congress on Antiphospholipid Antibodies Technical Task Force Report on Antiphospholipid Syndrome Clinical Features☆
Introduction
Antiphospholipid syndrome (APS) classification process is characterized by the presence of antiphospholipid antibodies (aPL), namely anticardiolipin antibodies (aCL), anti-beta 2 glycoprotein I (anti-b2GPI), or lupus anticoagulant (LA) associated with thrombosis of arteries or veins or the microcirculation and/or well defined obstetrical manifestations. However, to date there are no accepted criteria for diagnosis of this condition, although classification criteria tend to be used for definition and for diagnostic purposes. Current classification criteria for definite APS were established in a workshop, preceding the 11th International Congress on aPL in Sydney. These criteria derived from the Sapporo preliminary classification criteria for APS [1].
Several clinical manifestations associated with aPL are not included in the revised classification criteria [1]. Since the Congress in Sydney, a significant body of basic research and clinical studies on APS has appeared, bringing new data and an opportunity to revise clinical as well as laboratory manifestations. Considering these new data, the main goal of this task force was to examine the body of evidence related to the set of clinical manifestations that are not included in the current criteria and their association with aPL.
In this context, the Antiphospholipid Antibodies Task Force on Clinical Manifestations was carried out from January to September, 2013 to examine data, the quality of evidence according to GRADE system and develop recommendations in order to carefully suggest a revision of the current classification criteria [2]. A workshop held in Rio de Janeiro at the 14th International Antiphospholipid Congress discussed the findings [3], [4]. We examined all potential clinical criteria and selected the most relevant ones, we did not discuss the obstetrical manifestations, the future trends in treatment and the catastrophic APS which were evaluated by other groups [5], [6], [7].
Section snippets
Objectives
The objectives of this task force were: (1) to assess the patient-important outcomes that have been considered as non-criteria APS manifestations, and (2) to assess the body of evidence of each outcome to support the recommendation to be included on APS classification criteria.
Methodology
The PICO question was formulated as: “In patients with APS (P), are non-criteria APS manifestations (I) associated with APS classification, leading to earlier and most adequate treatment intervention to improve the patient-important outcomes (O)”?
We aimed to define and assess the outcomes that may be related to each non-criteria manifestation. An international group of APS experts of different specialties suggested non-criteria APS manifestations that were considered relevant. Some of the
Superficial vein thrombosis
PICO specific question: “In patients with APS, is superficial vein thrombosis associated with recurrent events, and would this criterion lead to earlier and most adequate treatment intervention to prevent the occurrence of recurrent thrombotic events, including serious life threatening events”?
PICO: P — APS; I/C — superficial vein thrombosis manifestations; O — the occurrence of recurrent thrombotic events, including serious life threatening event.
Discussion
A series of clinical features, that are not included in the classification criteria, but are recognized to be related to APS have been named non-classical or non-criteria clinical manifestations. An International Task Force reviewed those that were considered more clinically relevant, in addition to SN-APS, that although it is not consensus among the task force members, some considered it important to be investigated. We used the GRADE system to evaluate the medical literature on the relevance
Conclusion
The purpose of this task force was to critically analyze the so-called non-criteria manifestations of APS to support their inclusion as APS classification criteria. Classification criteria are important for including homogeneous groups of patients in observational as well as in therapeutic studies. The case has been made for including thrombocytopenia, renal microangiopathy, heart valve disease and two neurological manifestations (chorea and longitudinal myelitis) as classification criteria.
Take-home messages
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The purpose of this task force was to critically analyze the so-called non-criteria manifestations of APS to support their inclusion as APS classification criteria.
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Using GRADE system, we found that overall quality of evidence was very low for migraine and seizures,;low for superficial venous thrombosis, thrombocytopenia, chorea, longitudinal myelitis and the so-called seronegative APS, and moderate for APS nephropathy, heart valve lesions and livedo reticularis.
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A critical redefinition of an APS
Acknowledgment
This work was supported by the Brazilian Foundation for Higher Education Personnel Training Coordination (CAPES paep 2240/2013-40) & the Rio de Janeiro Research Foundation (FAPERJ: APQ2 110.023/2013).
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Dedication: The authors would like to dedicate this manuscript to the memory of Silvia Pierangeli.