Terrible APS - a newly defined variant of severe APS

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.

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.

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.

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.