Until recently, classification of antiphospholipid syndrome (APS) for clinical trials and studies was based on clinical and laboratory criteria described in the Sapporo classification criteria published in 1999,1 and revised in 2006.2
Given the limitations of the Sapporo criteria,3 and new data-driven and expert-based methodology available to develop classification criteria,4 an international effort jointly supported by the American College of Rheumatology (ACR) and the European Alliance of Associations for Rheumatology (EULAR), was initiated. The goal was to develop a new APS classification system, based on a more modern disease understanding, allowing for the weighting of individual criterion, and demonstrating excellent operating characteristics with the highest possible specificity. This international multidisciplinary effort included four phases: (1) criteria generation; (2) criteria reduction; (3) criteria definition, further reduction, and weighting via consensus-based multi-criteria decision analysis, and threshold identification; and (4) validation using independent adjudicators’ consensus as the ‘gold standard’.3 5
Novel clinical features of the new criteria include: (a) risk stratification of macrovascular events by traditional thrombosis risk factors; (b) well-defined microvascular domain items; (c) re-defined pregnancy morbidity definitions; and (d) the addition of cardiac valve disease and thrombocytopenia, to capture and quantify the magnitude of heterogeneous aPL manifestations. Novel laboratory features include: (a) quantifying single-, double-, and triple- antiphospholipid antibody (aPL) positivity based on different domains and weights; (b) separating anticardiolipin antibody (aCL)/anti-β2-Glycoprotein-I (aβ2GPI) IgG and IgM isotypes; and (c) defining two levels of aCL/aβ2GPI positivity that will be interpreted as clinically relevant by most investigators.5
In summary, the new (ACR/EULAR) APS classification criteria incorporate heterogenous aPL-related clinical and laboratory manifestations into a hierarchically clustered, weighted, and risk-stratified criteria reflecting current thinking about APS, providing high specificity and an improved foundation for APS research.
Wilson WA, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum. 1999 Jul;42(7):1309–11. doi: 10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F.
Miyakis S, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006 Feb;4(2):295–306. doi: 10.1111/j.1538-7836.2006.01753.x.
Barbhaiya M, et al. Development of a new international antiphospholipid syndrome classification criteria phase I/II report: generation and reduction of candidate criteria. Arthritis Care Res (Hoboken). 2021 Oct;73(10):1490–1501. doi: 10.1002/acr.24520. Epub 2021 Sep 2.
Johnson SR, et al. Classification criteria in rheumatic diseases: a review of methodologic properties. Arthritis Rheum. 2007 Oct 15;57(7):1119–33. doi: 10.1002/art.23018. Erratum in: Arthritis Rheum. 2007 Dec 15;57(8):1574.
Barbhaiya M, et al. 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumtol 2023 (in press).
Discuss the merits of the new APS classification system
Describe the presentation of heterogenous aPL-related clinical and laboratory manifestations and how these reflect current thinking about APS
Explain how the criteria provide an improved foundation for APS research
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