Addendum to QQ September 2026: Dr. Favaloro’s Reference

Antiphospholipid syndrome (APS) diagnosis is dependent on the 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 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria, the type of laboratory parameters remain essentially unchanged compared with the updated Sapporo classification criteria, and aCL and aβ2GPI measurement are still restricted to enzyme-linked immunosorbent assays (ELISAs) with moderate and high titer aPL thresholds defined as 40 and 80 Units, respectively, and a cutoff calculated by the 99th 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 ELISAs, the semiquantitative reporting of titers is a matter of debate, as well as the role of the isotypes immunoglobulin (Ig)M and IgA, and the role of other aPL, such as antiphosphatidylserine (aPS)/prothrombin (PT) 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.

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This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti‐Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three‐step procedure with two test systems (diluted Russell’s viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in‐house on at least 120 normals, with transference of the manufacturer’s cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.