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Rethinking antiphospholipid syndrome to guide future management and research

Nature Reviews Rheumatology (2024)Cite this article

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Abstract

Antiphospholipid syndrome (APS) consists of thrombotic, non-thrombotic and obstetric clinical manifestations developing in individuals with persistent antiphospholipid antibodies (aPL). Although researchers have made progress in characterizing different clinical phenotypes of aPL-positive people, the current approach to clinical management is still mostly based on a ‘one size fits all’ strategy, which is derived from the results of a limited number of prospective, controlled studies. With the 2023 publication of the ACR–EULAR APS classification criteria, it is now possible to rethink APS, to lay the groundwork for subphenotyping through novel pathophysiology-informed approaches, and to set a future APS research agenda guided by unmet needs in clinical management.

Key points

  • People with antiphospholipid syndrome (APS) can develop thrombotic, non-thrombotic and obstetric clinical problems in the persistent presence of antiphospholipid antibodies (aPL).

  • Definitions of APS vary in sophistication and have different purposes, such as describing APS to patients and learners, diagnosing and risk-stratifying patients in the clinic, or classifying patients for research purposes.

  • Future aims include better definition and subphenotyping of APS based on greater understanding of its underlying pathophysiology, using precisely defined autoantibodies, pathway-informed biomarkers, and modern genomic, transcriptomic and proteomic approaches.

  • Despite different clinical phenotypes among aPL-positive individuals, current management is mostly based on a ‘one size fits all’ strategy, derived from a limited number of prospective controlled studies.

  • The 2023 ACR–EULAR APS classification criteria should support a future research agenda aiming for better definition and subphenotyping of APS, and for more personalized and proactive management of all aPL-positive individuals.

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Authors and Affiliations

  1. Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA

    Jason S. Knight

  2. Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, USA

    Doruk Erkan

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  1. Jason S. Knight
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The authors contributed equally to all aspects of the article.

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Correspondence to Doruk Erkan.

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Competing interests

J.S.K. has received consulting fees from Argenix, Jazz Pharmaceuticals and Roivant Sciences, and is on the advisory board for Otsuka/Visterra. D.E. has received research grants from, GSK and Exagen, consulting fees from Argenix, Cadrenal and Chugai and royalties from Up-To-Date, and is on the speaker’s bureau for GSK and Aurinia, and the advisory boards for GSK and Otsuka/Visterra.

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Nature Reviews Rheumatology thanks Ariela Hoxha, who co-reviewed with Marco Lovisotto; Arsène Mékinian; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Knight, J.S., Erkan, D. Rethinking antiphospholipid syndrome to guide future management and research. Nat Rev Rheumatol (2024). https://doi.org/10.1038/s41584-024-01110-y

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