Laboratory Approaches to Test the Function of Antiphospholipid Antibodies

Abstract

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder caused by the presence of aPLs (antiphospholipid antibodies, i.e., anti-β2-glycoprotein I and anti-cardiolipin). Everyday practice in terms of laboratory diagnostics of APS includes determination of aPLs and well-known functional assays assessing for lupus anticoagulant (LA), in turn using various tests. According to recent guidelines, the recommended method for LA identification or exclusion is based on the Russell Viper Venom test and a sensitive activated partial thromboplastin time assay. Despite the fact that LA can be quantified in laboratory practice in this way, LA is still used as a binary parameter that is just one of the risk factors of thrombosis in APS. As of today, there are no other functional assays to routinely assess the risk of thrombosis in APS. It is well-known that APS patients display a wide range of clinical outcomes although they may express very similar laboratory findings. One way to solve this dilemma, could be if antibodies could be further delineated using more advanced functional tests. Therefore, we review the diagnostic approaches to test the function of aPLs. We further discuss how thrombin generation assays, and rotational thromboelastometry tests can be influenced by LA, and how experimental methods, such as flow cytometric platelet activation, surface plasmon resonance, or nano differential scanning fluorimetry can bring us closer to the puzzling interaction of aPLs with platelets as well as with their soluble protein ligand. These novel approaches may eventually enable better characterization of aPL, and also provide a better linkage to APS pathophysiology.

Testing for Lupus Anticoagulants

“…This article testifies that consensus has not been reached on all areas of LA detection and further work is needed. Thrombin generation assays are not yet ready to join the diagnostic analytical armoury, 149 but the author considers that there is a place for extending LA detection reper-toires beyond dRVVT and aPTT, such as the now validated TSVT/ET pairing as first line for VKA and DFXaI anticoagulated patients, and re-connecting with dPT to further improve detection rates. LA detection practices will continue to refine and evolve, it's been a fascinating journey so far, and there are more challenges ahead.…”