Intrinsic pathway activation in patients with antiphospholipid syndrome and healthy controls

Background: Antiphospholipid syndrome (APS) is a thrombotic autoimmune disease. Activation of the intrinsic coagulation pathway contributes to inflammatory and cardiovascular diseases, but its role in APS is unknown. Increased release of neutrophil extracellular traps and reduced effectiveness of direct oral anticoagulants support the hypothesis of increased intrinsic pathway activation in patients with APS, which is relevant considering the ongoing development and clinical testing of intrinsic pathway inhibitors. Objectives: To compare in vivo intrinsic pathway activation of patients with APS and healthy controls. Methods: Patients with APS without recent thrombotic or obstetric events and healthy controls were investigated. ELISAs were used to measure activated coagulation factors in complex with the natural inhibitors antithrombin or C1-esterase inhibitor in plasma. The primary outcome of this study was factor (F)XII activation, which initiates the intrinsic pathway. Secondary outcomes included activation of downstream intrinsic coagulation FXI and FIX. Results: Plasma of 73 patients with APS and 19 healthy controls showed no significant difference in activated FXII-inhibitor complexes. The concentrations of activated FXI and FIX and inhibitor complexes likewise did not differ between the groups. A subanalysis of patients with APS by anticoagulant use showed no difference for FXII and FXI activation. Conclusion: Intrinsic pathway activation in patients with APS without recent thrombotic or obstetric events did not differ significantly compared with healthy controls.