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. 2025 Jan 31;9(1):102694.
doi: 10.1016/j.rpth.2025.102694. eCollection 2025 Jan.

Intrinsic pathway activation in patients with antiphospholipid syndrome and healthy controls

Dagmar J M van Mourik  1   2   3 , Valérie L B I Jansen  1   2   4 , Michiel Coppens  1   2 , Saskia Middeldorp  5 , Hugo Ten Cate  6 , Harry R Büller  1   2 , Henri M H Spronk  6   7 , Magdolna Nagy  7 , Thijs E van Mens  1   2   3   4
Affiliations

Intrinsic pathway activation in patients with antiphospholipid syndrome and healthy controls

Dagmar J M van Mourik et al. Res Pract Thromb Haemost. .

Abstract

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.

Keywords: antiphospholipid syndrome; coagulation cascade; factor XII; intrinsic pathway; thrombotic autoimmune disease.

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Figures

Figure 1
Figure 1
Factor (F)XII activation. Activated FXII was determined in complex with antithrombin (FXIIa-AT) (A) and C1-esterase inhibitor (FXIIa-C1Inh) (B) in patients with antiphospholipid syndrome (APS; n = 72) and healthy controls (n = 19). A subanalysis measured FXIIa-AT (C) and FXIIa-C1Inh (D) in patients with APS using direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs; n = 39) and in patients with APS without anticoagulants (n = 32). A second subanalysis determined FXIIa-AT (E) and FXIIa-C1Inh (F) in thrombotic patients with APS (TRAPS; n = 52) and in obstetric patients with APS (OAPS; n = 20). Data are expressed as median with interquartile range. For statistical analysis, the data were log-transformed and analyzed using an independent t-test.
Figure 2
Figure 2
Factor (F)XI and IX activation. Activated FXI was determined in complex with antithrombin (FXIa-AT) (A) and C1-esterase inhibitor (FXIa-C1Inh) (B) in patients with antiphospholipid syndrome (APS; n = 73) and healthy controls (n = 19). A subanalysis measured FXIa-AT (C) and FXIa-C1Inh (D) in patients with APS using direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs; n = 40) and in patients with APS without anticoagulants (n = 32). Activated FIX was measured in complex with antithrombin (FIXa-AT) (E) in patients with APS (n = 73) and healthy controls (n = 19). A subanalysis determined FIXa-AT (F) in patients with APS using anticoagulants, DOAC or VKA (n = 40), and in patients with APS without anticoagulant medication (n = 32). Data are expressed as median with interquartile range. For statistical analysis, the data were log-transformed and analyzed using an independent t-test, ∗∗P ≤ .010.
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References

    1. Miyakis S., Lockshin M.D., Atsumi T., Branch D.W., Brey R.L., Cervera R., et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) J Thromb Haemost. 2006;4:295–306. - PubMed
    1. Gaspar P., Sciascia S., Tektonidou M.G. Epidemiology of antiphospholipid syndrome: macro- and microvascular manifestations. Rheumatol (Oxf Engl) 2024;63:SI24–SI36. - PMC - PubMed
    1. Meroni P.L., Borghi M.O., Raschi E., Tedesco F. Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol. 2011;7:330–339. - PubMed
    1. Schreiber K., Sciascia S., de Groot P.G., Devreese K., Jacobsen S., Ruiz-Irastorza G., et al. Antiphospholipid syndrome. Nat Rev Dis Primers. 2018;4 - PubMed
    1. Cuadrado M.J., López-Pedrera C., Khamashta M.A., Camps M.T., Tinahones F., Torres A., et al. Thrombosis in primary antiphospholipid syndrome: a pivotal role for monocyte tissue factor expression. Arthritis Rheum. 1997;40:834–841. - PubMed

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