{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T17:34:06Z","timestamp":1787506446691,"version":"build-2736575974"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Antiphospholipid syndrome (APS) presents with various clinical features and some patients exhibit progressive, refractory disease that does not meet the catastrophic APS (cAPS) criteria. This study describes a new subcategory of APS patients, \u201cTerrible APS\u201d (TrAPS), characterized by recurrent thrombosis despite optimal anticoagulation, often requiring immunomodulation or surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 306 primary APS patients, excluding those with obstetric, non-criteria APS, or cAPS. TrAPS was defined as &amp;gt;2 breakthrough thrombotic events despite anticoagulation (without provocation or cardiovascular risk) or the need for &amp;gt;1 immunomodulatory or surgical intervention.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 209 patients with thrombotic primary APS, 27 (12.7%) met the TrAPS criteria. These patients had higher rates of venous thrombosis, microvascular involvement, heart valve disease, thrombocytopenia, and triple-positive antiphospholipid antibodies. TrAPS was associated with\n                      <jats:italic>increased mortality<\/jats:italic>\n                      (18.5%\n                      <jats:italic>vs<\/jats:italic>\n                      . 5.1%) and anticoagulant resistance (81.4% with breakthrough events). Based on multivariate analysis, we identified four key predictors that formed the basis of the TrAPScore: severe thrombocytopenia (&amp;lt;50,000, 4 points), heart valve involvement (4 points), microvascular manifestations (3 points), and triple-positive serology (2 points). A TrAPScore &amp;gt;6 had a positive predictive value (PPV) of 78%\u201382.5%, while a score &amp;lt;4 had a negative predictive value (NPV) of 96.9% for TrAPS diagnosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>We herein individualized a particularly refractory APS subcategory, TrAPS. The TrAPScore incorporates severe thrombocytopenia, heart valve disease, microvascular manifestations, and triple-positive serology. A TrAPS score &amp;gt;6 predicted a high likelihood of severe, refractory disease while effectively excluding TrAPS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2025.1721515","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T06:59:24Z","timestamp":1767769164000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Terrible APS \u2014 a newly defined variant of severe APS"],"prefix":"10.3389","volume":"16","author":[{"given":"Stanley","family":"Niznik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Zaher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soad","family":"Haj 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