Challenges of laboratory testing in patients suspected of antiphospholipid syndrome: practical implications for clinicians

This paper focuses on laboratory tests necessary for a diagnosis of antiphospholipid syndrome (APS). The diagnosis starts with a selection of patients suspected of APS. Timing related to a clinical event is important to avoid false classification of APS patients. To correctly interpret the test results for antiphospholipid antibodies (aPL), it is necessary to understand all possible pitfalls and interferences. Lupus anticoagulant (LA) measurement remains a complex procedure with many challenges. The effect of anticoagulant therapy, the main confounder of LA measurement, can be overcome by removal agents for direct oral anticoagulants (DOACs) or by considering assays such as Taipan snake venom time / Ecarin clotting time not affected by antivitamin K therapy and anti -Xa DOACs. However, both procedures have limitations. Solid -phase assays for anticardiolipin antibodies (aCL) and anti -beta 2 glycoprotein I antibodies (a beta 2GPI) show interassay differences. Diagnosis is based on the measurement of 3 groups of aPL: LA, aCL, and a beta 2GPI, of immunoglobulin (Ig) G and IgM isotype. This allows the clinicians for developing antibody profiles that help identify patients at risk. Other aPL, such as antibodies against domain I of beta 2GPI and anti -phosphatidylserine / prothrombin antibodies may be useful in risk stratification of APS patients, and in some specific situations of patients with an incomplete antibody profile, but are not needed for diagnosis. Laboratory diagnosis of APS remains challenging. To increase the diagnostic efficacy and reliability, an integrated interpretation of all results and an interpretative comment should be provided on the laboratory report. Therefore, a close interaction between clinical pathologists and clinicians is mandatory.