An update on laboratory detection and interpretation of antiphospholipid antibodies for diagnosis of antiphospholipid syndrome: Guidance from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee (ISTH-SSC) Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies.

Abstract

APS diagnosis is dependent on accurate detection and interpretation of antiphospholipid antibodies (aPL). Lupus anticoagulant (LA), anticardiolipin antibodies (aCL) and anti-beta2 glycoprotein I antibodies (aβ2GPI) remain the cornerstone of the laboratory part of APS diagnosis. In the 2023 ACR/EULAR APS classification criteria, the type of laboratory parameters remain essentially unchanged compared to the updated Sapporo classification criteria, and aCL and aβ2GPI antibody measurement is still restricted to enzyme-linked immunosorbent assays (ELISA) with moderate and high titer aPL thresholds defined as 40 and 80 units, respectively, and a cutoff calculated by the 99^th percentile has been abandoned. We must differentiate between classification criteria and assessment of aPL in clinical care. Classification criteria are strict and meant for participant inclusion in studies and trials to study homogeneous populations of patients. In contrast, laboratory detection for APS diagnosis in daily practice is broader meant to diagnose each APS patient to optimize their management. Nowadays, there is increasing use of measurement of aPL by methods other than ELISA, the semiquantitative reporting of titers is a matter of debate, as well as the role of the isotypes IgM and IgA, and the role of other aPL, such as antiphosphatidylserine/prothrombin antibodies. Patients diagnosed with the disease may or may not fulfill the classification criteria and inappropriate use of classification criteria may lead to mis(under)diagnosis. The aim of this guidance, based on literature and expert opinion, is to provide guidance recommendations for laboratory workers and clinicians, on routine diagnostic assessment of patients with suspected APS.