Activated Protein C Sensitivity Assessed with Thrombin Generation Assay in Antiphospholipid Syndrome Women: Results from Two French Cohorts

Abstract

Background

Antiphospholipid syndrome (APS) is an autoimmune condition with thrombotic and/or obstetric manifestations (tAPS and oAPS respectively). Impaired sensitivity to activated protein C (APC), often referred to as “acquired APC resistance,” is known to be an independent risk factor for thrombosis across a variety of conditions. In particular it has been implicated in the prothrombotic phenotype of APS and may serve as a prognostic marker in tAPS. However, data on APC sensitivity in oAPS remain inconclusive.

Methods

We included 60 women less than 50 years of age from two prospective French cohorts with neither overlapping manifestations nor associated autoimmune diseases. APC sensitivity was assessed using calibrated automated thrombography with platelet-rich plasma. APC sensitivity ratio (APCsr) was defined as the ratio of endogenous thrombin potential (ETP) in the presence of 25 nM APC (ETP-APC25) to ETP in its absence (ETP0).

Results

A total of 60 women was analyzed (43 tAPS and 17 oAPS); 15 tAPS women received anticoagulant treatment. No difference in APCsr was observed between tAPS and oAPS patients. In anticoagulated tAPS women, ETP0 and ETP-APC25 levels were, as expected, significantly lower than non-anticoagulated women, but APCsr remained consistent in identifying patients with high-risk serological profile.

Conclusion

Our findings suggest that decreased APC sensitivity is shared by the two main APS clinical phenotypes, which hence must have distinct pathogenic alterations as well. APC sensitivity can be investigated with CT even if clotting times are prolonged (lupus anticoagulant effect) and if thrombin generation is decreased as a result of anticoagulant treatment.

Keywords

antiphospholipid syndrome - obstetric - activated protein C - activated protein C sensitivity

Publication History

Received: 04 November 2025

Accepted after revision: 18 January 2026

Article published online:
28 January 2026

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