The 2023 ACR/EULAR Classification Criteria for Antiphospholipid Syndrome: Implications for the Inclusion of Participants in Research vs Diagnosis in Clinical Practice

Abstract

Antiphospholipid syndrome (APS) was first described in patients with systemic lupus erythematosus in 1983, and the primary version in 1989. Multiple clinical manifestations have been associated with antiphospholipid antibodies (aPL) including venous and arterial thromboses, transient ischemic attack (TIA), obstetric complications, thrombocytopenia, hemolytic anemia, livedo reticularis, transverse myelitis, cognitive dysfunction, cutaneous ulcers, Libman-Sacks endocarditis, and a peculiar type of nephropathy. Antiphospholipid antibodies include lupus anticoagulant (LAC), anticardiolipin antibodies  (aCL) IgG and IgM, and anti‑beta‑2‑glycoprotein antibodies (aβ₂GPI) IgG and IgM. Other antibodies such as anti-prothrombin and anti-prothrombin/phosphatidylserine have been proposed as biomarkers of APS, particularly in cases where the standard antibodies are negative, but they are not officially accepted.

Since 1999, the original Sapporo Criteria and its revised 2006 version have been used for the classification of patients in research studies and for the diagnosis of patients with APS. Despite the broad spectrum of clinical manifestations and serological markers considered by physicians as part of the APS, the original and revised versions of Sapporo Criteria include only venous, arterial and microvascular thrombotic events and specific obstetric events among the clinical manifestations, and aCL IgG and IgM antibodies, aβ₂GPI-I antibodies IgG and IgM or lupus anticoagulant as the serological markers. Consequently, APS was diagnosed as obstetric and/or thrombotic syndrome, not considering other non-criteria manifestations associated to aPL antibodies. The major limitation of these criteria is that they do not reflect the systemic nature of APS.

Due to the importance of classification criteria in research, the ACR and EULAR assumed the responsibility of encouraging the development and validation of new and improved classification criteria for various rheumatic diseases, including APS, based on the current standards of measurement.