Laboratory testing for the antiphospholipid syndrome: making sense of antiphospholipid antibody assays

Abstract

The antiphospholipid syndrome (APS) is an autoimmune condition characterised by a wide range of clinical features (primarily thrombosis and/or obstetric related), associated with the presence of antiphospholipid antibodies (aPL) as detected by a diverse range of laboratory tests. APS remains a significant diagnostic challenge for clinicians across a wide range of specialities, largely due to issues related to laboratory testing as well as the expanding range of reported clinical manifestations of APS. The laboratory issues include limitations in detailed knowledge by both clinical and laboratory personnel regarding the ‘complete’ range of available aPL tests, as well as ongoing problems with assay reproducibility and standardisation. aPL are identified using diverse laboratory procedures based on one of two distinct test processes, namely solid phase and liquid phase assays. The former includes anticardiolipin antibodies (aCL) and anti-β₂-glycoprotein I antibodies (aβ₂GPI). The latter are centred on clot-based tests that are used to identify the so-called lupus anticoagulant (LA). This article will discuss: (i) issues related to laboratory testing for APS in terms of the currently available solid-phase and liquid-phase assays, and identifiable biases resulting from these tests usually being performed in different laboratories; (ii) current problems with calibration, standardisation and reproducibility of these assays; (iii) pre-analytical, analytical and post-analytical considerations and ongoing initiatives for improvement; (iv) issues related to potential combinations/panels of available aPL tests; and (v) the entities of seropositive APS, seronegative APS and non-APS aPL-positivity. In doing so, this review will hopefully help bridge the two disciplines of haematology and immunology (‘representing’ liquid-phase and solid-phase aPL testing, respectively), by improving the understanding of those working in each of these disciplines of the merits and limitations of the assays performed in the other discipline, and encouraging inter-discipline cooperation in the reporting of aPL test results.