Development of 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria, Phase III-A/B Report: Defining and Structuring the Clinical and Laboratory Domains.

PURPOSE OF REVIEW: An international multi-disciplinary initiative resulted in the development of 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification Criteria to identify patients with high likelihood of APS for research. Phase I/II resulted in 27 candidate criteria organized into six clinical and laboratory domains. Here, we summarize early Phase III efforts to better define and structure candidate criteria within clinical and laboratory domains.

RECENT FINDINGS: Using comprehensive literature reviews and expert consensus, domain subcommittees developed definitions for candidate criteria. Prevalence information was incorporated when available. Definitions were finalized and approved by the Steering Committee for future use during real-world case collection (derivation cohort), multi-criteria decision analysis, and validation. Clinical domain items defined were: (a) macrovascular thrombosis (venous thromboembolism including superficial venous thrombosis, arterial thrombosis, and transient ischemic attack) and associated provoking risk factors; (b) microvascular disease (livedo racemosa, livedoid vasculopathy, antiphospholipid-antibody-nephropathy, diffuse alveolar hemorrhage, cardiac microthrombosis, adrenal hemorrhage, and acute ischemic encephalopathy); (c) pregnancy morbidity (pre-fetal death, fetal death, and pre-eclampsia and placental insufficiency with severe features); (d) cardiac valve disease (thickening or vegetation); and (e) thrombocytopenia. Laboratory domain items defined were coagulation-based functional assay (lupus anticoagulant) and solid phase-based assays (anticardiolipin antibody IgG/M and anti-β2-Glycoportein-I antibody IgG/M). Based on comprehensive literature review and Steering Committee consensus, we defined and structured APS clinical and laboratory domains. Preliminary definitions were subsequently evaluated and confirmed in late Phase III using the derivation cohort and multicriteria decision analysis prior to validation the 2023 ACR/EULAR APS Classification Criteria.