Prevalence and prognostic value of activated protein C resistance and anti-protein C antibodies in patients with antiphospholipid antibodies: an APS ACTION Registry study
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ID: 317442
2026
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Abstract
OBJECTIVES: The clinical significance of acquired resistance to activated protein C (APCr) and antibodies against protein C (anti-PC) in antiphospholipid syndrome (APS) has not been established. This study sought to determine the prevalence of APCr and anti-PC, associations with aPL profile and clinical phenotypes, and exploratory associations with subsequent thrombosis. METHODS: Three-hundred and seventy patients persistently positive for antiphospholipid antibodies (aPL) with/without APS (aPL-only (n = 77), pregnancy morbidity (PM, n = 43), venous thromboembolism (VTE, n = 132), arterial thrombosis (AT, n = 87), or VTE+AT (n = 31) and 51 healthy controls were studied. Baseline APCr was determined using thrombin generation with recombinant human APC (rhAPC) or Protac®. Anti-PC and avidity were detected by in-house ELISA. RESULTS: All patient subgroups had markedly greater APCr compared to healthy controls (p < 0.001), with greatest APCr observed in VTE+AT or triple aPL-positive patients. Anti-PC were present in 42% of patients, with VTE+AT exhibiting significantly higher prevalence of high avidity anti-PC (79%) compared to aPL-only patients (38%) (p < 0.05). During prospective follow-up of 283 patients from the APS ACTION Registry (median 8.3 years), 25/283 (8.8%) had new thrombosis, with similar incidence between patients with or without APCr or anti-PC (p > 0.60). Non-anticoagulated patients with APCr had more thrombotic events compared to those without, although not statistically significant (HR 4.5, 95% CI 0.8-25.9, p = 0.14). CONCLUSION: High prevalence of APCr was seen across all aPL-positive patients, strongly associated with high avidity anti-PC. Lack of association with thrombosis may reflect confounding by baseline anticoagulation and limited events. The association of APCr with thrombosis in non-anticoagulated patients merits further exploration.
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| Authors | Ibrahim Tohidi‐Esfahani, Veronica Venturelli, MARIA TEKTONIDOU, Vittorio Pengo, Diana Parades-Ruiz, D Ware Branch, Maria Gerosa, Cecilia Nalli, Esther Rodríguez-Almaraz, Michelle Petri, Ricard Cervera, Olga Amengual, Danieli de Andrade, R. Willis, María Laura Bertolaccini, Doruk Erkan, Hannah Cohen, Maria Efthymiou |
| Journal | Lara D. Veeken |
| Year | 2026 |
| DOI |
10.1093/rheumatology/keag304
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| URL | |
| Keywords | Keywords not found |
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