Rheumatology (Oxford, England) · 2026
Prevalence and prognostic value of activated protein C resistance and anti-protein C antibodies in patients with aPLs: an APS ACTION Registry study.
СтатьяПоддержка исследования: вне правительства СШАПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Tohidi-Esfahani Ibrahim, Venturelli Veronica, Tektonidou Maria, Pengo Vittorio, Parades-Ruiz Diana, Branch D Ware, Gerosa Maria, Nalli Cecilia, Rodriguez Almaraz Esther, Petri Michelle, Cervera Ricard, Amengual Olga, Andrade Danieli de, Willis Rohan, Bertolaccini Maria Laura, Erkan Doruk, Cohen Hannah, Efthymiou Maria
Аннотация
OBJECTIVES: The clinical significance of acquired resistance to activated protein C (APCr) and antibodies against protein C (anti-PCs) in APS has not been established. This study sought to determine the prevalence of APCr and anti-PCs, associations with aPL profile and clinical phenotypes, and exploratory associations with subsequent thrombosis.
METHODS: Three-hundred and seventy patients persistently positive for aPLs with/without APS (aPL-only, n = 77), obstetric APS (OAPS, 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-PCs and avidity were detected by in-house ELISA.
RESULTS: All patient subgroups had markedly greater APCr compared with healthy controls (P < 0.001), with the greatest APCr observed in VTE + AT or triple aPL-positive patients. Anti-PCs were present in 42% of patients, with VTE + AT exhibiting significantly higher prevalence of high-avidity anti-PCs (79%) compared with 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 incidences between patients with or without APCr or anti-PCs (P > 0.60). Non-anticoagulated patients with APCr had more thrombotic events compared with those without, although the difference was not statistically significant (hazard ratio 4.5, 95% CI 0.8-25.9, P = 0.14).
CONCLUSION: A high prevalence of APCr was seen across all aPL-positive patients, strongly associated with high-avidity anti-PCs. 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.
METHODS: Three-hundred and seventy patients persistently positive for aPLs with/without APS (aPL-only, n = 77), obstetric APS (OAPS, 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-PCs and avidity were detected by in-house ELISA.
RESULTS: All patient subgroups had markedly greater APCr compared with healthy controls (P < 0.001), with the greatest APCr observed in VTE + AT or triple aPL-positive patients. Anti-PCs were present in 42% of patients, with VTE + AT exhibiting significantly higher prevalence of high-avidity anti-PCs (79%) compared with 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 incidences between patients with or without APCr or anti-PCs (P > 0.60). Non-anticoagulated patients with APCr had more thrombotic events compared with those without, although the difference was not statistically significant (hazard ratio 4.5, 95% CI 0.8-25.9, P = 0.14).
CONCLUSION: A high prevalence of APCr was seen across all aPL-positive patients, strongly associated with high-avidity anti-PCs. 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.