Added value of antiphosphatidylserine/prothrombin antibodies in the workup of thrombotic antiphospholipid syndrome: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies

Vandevelde, Arne, Chayoua, Walid, de Laat, Bas, Moore, Gary W. ORCID: https://orcid.org/0000-0002-2987-281X, Musiał, Jacek, Zuily, Stéphane, Wahl, Denis and Devreese, Katrien M. J. (2022) Added value of antiphosphatidylserine/prothrombin antibodies in the workup of thrombotic antiphospholipid syndrome: Communication from the ISTH SSC Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. Journal of Thrombosis and Haemostasis, 20 (9) . pp. 2136-2150. ISSN 1538-7933 [Article] (doi:10.1111/jth.15785)

Abstract

Background
Diagnosis of antiphospholipid syndrome (APS) requires persistent presence of lupus anticoagulant (LAC), anticardiolipin (aCL) IgG/IgM, or anti-β2 glycoprotein I (aβ2GPI) IgG/IgM antibodies. Other antiphospholipid antibodies (aPL) such as antiphosphatidylserine/prothrombin antibodies (aPS/PT) are promising in assessment of thrombotic APS (TAPS).

Aim
To evaluate the added value of aPS/PT IgG and IgM in TAPS.

Material and methods
aPS/PT IgG/IgM, aCL IgG/IgM, aβ2GPI IgG/IgM, and LAC were determined in 757 patients (TAPS and controls). aPS/PT cut-off values were calculated, aPS/PT titers and positivity were compared between TAPS and controls, type of thrombosis, and antibody profiles. Likelihood ratios (LR), odds ratios (OR) and aPL-score were determined.

Results
aPS/PT IgG and IgM were associated with TAPS and triple positivity. In-house calculated cut-offs were higher for IgM (43 units), compared to manufacturer’s cut-off (30 units). Thresholds of 90 (IgG)/200 (IgM) units were determined as high-titer cut-off. Higher aPS/PT titers were observed in triple positive patients and showed higher LR and OR for TAPS. aPS/PT was independently associated with TAPS when adjusted for aCL/aβ2GPI, but not when adjusted for LAC. In isolated LAC positive patients, aPS/PT was positive in 27.1% TAPS patients and in 77.3% patients with autoimmune disease. Diagnostic value of aPL-score did not differ with and without including aPS/PT.

Conclusion
aPS/PT positivity, especially with high antibody titer, is associated with TAPS diagnosis. Analysis on top of current laboratory criteria is not essential in TAPS diagnosis, but aPS/PT could be useful in patients with thrombosis and a double positive aPL profile (aCL+/aβ2GPI+).

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