ArticleRheumatology (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.
Article in Rheumatology (Oxford, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesThe 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.
methodsThree-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.
resultsAll 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).
conclusionA 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.
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