An aPL fill was crudely calculated as the sum of four test results (IgG aCL, IgM aCL, IgG anti-2GPI, IgM anti-2GPI). Congress on aPL, Manchester, UK, September 2019. Keywords: Phosphatidylserine-dependent antiprothrombin antibodies, antibodies to domains of 2-glycoprotein-I, anti-2Glycoprotein-I antibodies Introduction Classification criteria for antiphospholipid syndrome (APS) require IgG or IgM isotypes of the anticardiolipin TA 0910 acid-type (aCL) antibodies, anti-2-glycoprotein I (anti-2GPI) antibodies, and/or the lupus anticoagulant (LA) to satisfy the laboratory criterion for disease definition. 1 Over the past years several non-criteria antiphospholipid antibodies (aPL), directed to proteins of the coagulation cascade (i.e., prothrombin and/or phosphatidylserineCprothrombin complex) or to specific domains of 2GPI have been focused upon.2,3 The task force on antiphospholipid syndrome laboratory diagnostics and trends focused and reviewed the literature on data including aPS/PT, antibodies to domain 4/5 of 2GPI and the newly described antibodies to protein/HLA-DR complex. In addition, TA 0910 acid-type we discussed testing of LA in the new oral anticoagulants era and the value of triple positivity in the risk assessment of aPL. The conclusions were ITSN2 presented at a special session during the 16th International Congress on aPL, Manchester, UK, September TA 0910 acid-type 2019 and updated previous to this publication. Phosphatidylserine-dependent Antiprothrombin Antibodies (aPS/PT) Many reports show the clinical utility of phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) assay in the diagnosis of APS. The inclusion of aPS/PT antibodies as a laboratory criterion of APS has been previously considered by our task force and deemed unwarranted because of poor standardization of the available assays and because reproducibility of the strong correlations between aPS/PT and APS manifestations needed confirmation in larger studies. 4 Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are a low affinity heterogeneous class of antibodies directed against a complex of negatively charged phospholipid, other than cardiolipin and prothrombin (PT). The methodology for their detection has improved over the years and currently aPS/PT antibodies are identified by enzyme immunosorbent assays using prothrombin in complex with phosphatidylserine in the presence of calcium. Calcium ion aids the binding of prothrombin to phosphatidylserine inducing major conformational changes to the prothrombin structure which, in turn, TA 0910 acid-type exposes cryptic or neo-epitopes that act as target for aPS/PT. 5 The site of binding on the prothrombin molecule is still under research and it may be possible that different types of antibodies can recognize different sites of the prothrombin molecule. 6 So far, it has been established that aPS/PT and aPT represent two different types of antibodies that can be present concurrently in some cases. 7 Prothrombin 1 and fragment 1 and fragment 1+2 have been reported as potential antigens recognized by antiprothrombin antibodies, suggesting that the dominant epitopes are likely to be located near the phospholipid-binding site of the prothrombin molecule. 5 A recent study by Chinnaraj and colleagues used prothrombin mutants and identified 2 subpopulations of aPS/PT, namely type I and type II, which engage fragment 1 of prothrombin at different epitopes. 8 Testing for aPS/PT antibodies has been proposed as an additional tool to be considered when investigating a patient suspected of having APS, particularly in the absence of routine aPL positivity,2,9 or as a part of risk assessment strategies. 10 aPS/PT represent in fact a stronger risk factor for thrombosis, both arterial and/or venous, than aPT 11 and in combination with LA and anti-2GPI offer the best diagnostic indication of APS. 12 This is supported by a recent study by Pengo and colleagues, that demonstrated that the search for aPS/PT antibodies along anti-2GPI antibodies, in patients positive for LA, might be useful to identify two distinct subgroups of patients at different risk of thromboembolic events. 13 In addition, patients with triple positivity for LA, anti-2GPI and aPS/PT have been shown to be at a higher risk of developing thromboembolic events, risk even higher than that seen for the classical aCL, anti-2GPI, and LA triple positivity.12,14 An early systematic review evaluated papers from 1988 to 2013 and assessed the correlation between aPT and aPS/PT antibodies and the risk of thrombosis. 11 Among 10 studies on aPS/PT, comprehensive of 1775 patients and 628 controls, eight of them confirmed the association with thrombosis, but only seven compared the ORs. When performed, multivariate analysis sustained aPS/PT correlation with thrombosis and venous events. The correlation was confirmed in a more recent systematic review 15 that analyzed the studies on aPS/PT and their correlation with clinical manifestations of APS.
