ORIGINAL RESEARCH article
Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
This article is part of the Research TopicAntibody-Mediated Thrombotic DiseaseView all 5 articles
Terrible APS (TrAPS) - A newly defined variant of severe APS
Provisionally accepted
Stanley Niznik1*
Tania Zaher2
Soad Haj Yahia1,3Ronen Shavit1,3Shiri Weinstein1Yulia lifshitz-Tunitsky1
NANCY AGMON-LEVIN1,3- 1Zabludowicz Center for Autoimmune Diseases & Rheumatology Unit, Sheba Medical Center, Ramat Gan, Israel
- 2City St George's University of London - Tooting Campus, London, United Kingdom
- 3Tel Aviv University Faculty of Medical and Health Sciences, Tel Aviv-Yafo, Israel
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Introduction - Antiphospholipid syndrome (APS) presents with various clinical features; some patients exhibit progressive, refractory disease not meeting catastrophic APS (cAPS) criteria. This study describes new subcategory in APS patients - "Terrible APS" (TrAPS), characterized by recurrent thrombosis despite optimal anticoagulation, often requiring immunomodulation or surgery. Methods - We analyzed 306 primary APS patients, excluding those with obstetric, non-criteria APS, or cAPS. TrAPS was defined by >2 breakthrough thrombotic events despite anticoagulation (without provocation or cardiovascular risk), or the need for >1 immunomodulatory or surgical intervention. Results - Among 209 thrombotic primary APS patients, 27 (12.7%) met the TrAPS criteria. These patients showed higher rates of venous thrombosis, microvascular involvement, heart valve disease, thrombocytopenia, and triple-positive antiphospholipid antibodies. TrAPS was associated with increased mortality (18.5% vs. 5.1%) and anticoagulation resistance (81.4% with breakthrough events). Based on multivariate analysis we have identified four key predictors which formed the basis of the TrAPScore: severe thrombocytopenia (<50,000, 4 points), heart valve involvement (4 points), microvascular manifestations (3 points), and triple-positive serology (2 points). A TrAPScore >6 had positive predictive value (PPV) of 78-82.5%, while a score <4 had a negative predictive value (NPV) of 96.9% for TrAPS diagnosis. Conclusion – We herein individualised a particularly refractory APS subcategory – Named TrAPS. TrAPScore incorporate severe thrombocytopenia, heart valve disease, microvascular manifestation and triple positive serology. TrAPS score >6 predicted a high likelihood of severe, refractory disease while effectively excluded TrAPS.
Keywords: Antiphospholipid syndrome (APS), microvascular disease, Heart valve disease, Anti-phospholipid antibodies, traps
Received: 09 Oct 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 Niznik, Zaher, Haj Yahia, Shavit, Weinstein, lifshitz-Tunitsky and AGMON-LEVIN. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Stanley Niznik
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