Antiphospholipid antibodies: evaluation of the thrombotic risk

Abstract

The laboratory diagnosis of the antiphospholipid syndrome (APS) via antiphospholipid antibody (aPL) tests, including lupus anticoagulant (LAC), anti-cardiolipin (aCL), or anti-beta2 glycoprotein I (aβ2GPI) antibodies remains a challenge. Coagulation tests for LAC as well as solid phase assays for aCL and aβ2GPI have methodological shortcomings, although for LAC large progress have been made in standardization. All assays are associated with clinical APS-criteria (thrombotic and/or pregnancy complications) but with limited specificity. Besides, clinical studies demonstrating the association between the presence of aPL and thrombosis are not always well designed and result in wide ranges of odds ratio with large variation between studies. The best association between thrombotic complications and aPL is found for LAC. The association between thrombosis and aCL or aβ2GPI is at least inconsistent. The inclusion of more specific assays, such as the domain-I-β2GPI.antibodies is too premature and depends on further investigation in large clinical studies and the commercial availability. The search for new assays should proceed to identify patients with aPL with increased risk for thrombosis, preferable in large prospective studies. Meanwhile, with the current available LAC, aCL and aβ2GPI assays it is strongly recommended to make antibody profiles. Multiple positivity of tests seems clinically more relevant. The strengths and weaknesses of the current laboratory criteria for APS are discussed in view of their role in risk stratification of patients with thrombotic events.