Terrible APS - a newly defined variant of severe APS.

Introduction: 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, "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 as >2 breakthrough thrombotic events despite anticoagulation (without provocation or cardiovascular risk) or the need for >1 immunomodulatory or surgical intervention. Results: 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 increased mortality (18.5% vs. 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 (<50,000, 4 points), heart valve involvement (4 points), microvascular manifestations (3 points), and triple-positive serology (2 points). A TrAPScore >6 had a 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 individualized a particularly refractory APS subcategory, TrAPS. The TrAPScore incorporates severe thrombocytopenia, heart valve disease, microvascular manifestations, and triple-positive serology. A TrAPS score >6 predicted a high likelihood of severe, refractory disease while effectively excluding TrAPS.