PB0434 - Role of contact activation pathway in antiphospholipid syndrome: a case-control study

Sunday, June 25, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Dagmar J.M van Mourik, MSc

PhD student
Amsterdam UMC location University of Amsterdam
Amsterdam, Noord-Holland, Netherlands

Co-Author(s)

Valérie L.B.I. Jansen, MD

MD PhD student
Amsterdam UMC location University of Amsterdam, Vascular Medicine, Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands
Michiel Coppens, MD, PhD (he/him/his)

Medical Specialist
Amsterdam University Medical Centers, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Saskia Middeldorp, MD PhD

Professor
Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands
Nijmegen, Gelderland, Netherlands
HB

Harry R. Büller

MD
Department of Vascular Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
HS

Henri M.H. Spronk

Chief Executive Officer
Coagulation Profile, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Magdolna Nagy, PhD

Postdoctoral Researcher
Coagulation Profile, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Tv

Thijs E. van Mens

PhD, MD
Amsterdam UMC location University of Amsterdam, Vascular Medicine, Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands

Background: Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia. APS antibodies have a range of effects on the coagulation system contributing to the prothrombotic state. However, the relative contribution of the contact activation pathway to the pathogenesis has not been elucidated. Given the prominent role of neutrophil extracellular traps (NETs) in APS and the role of NETs in coagulation, contact activation may contribute to the prothrombotic state.

Aims: To assess the contact activation pathway in APS patients compared to healthy controls.

Methods: We included thrombotic and/or obstetric APS diagnosed patients according to the Sydney classification criteria and healthy controls from our APS biobank. Subjects had no recent clinical events. Contact activation and downstream activation were assessed by measuring coagulation enzyme:inhibitor complexes in platelet-poor plasma. Activated coagulation factor XII:antithrombin (FXIIa:AT), FXIIa:C1-inhibitor (FXIIa:C1Inh), FIXa:AT and thrombin (T):AT complexes were measured utilizing novel in-house developed ELISAs. Our primary outcome was total FXII activation as measured by the sum of FXIIa:AT and FXIIa:C1Inh. Concentrations were log-transformed to achieve normal distribution and compared using independent t-test.

Results: We included 73 APS patients and 19 age-matched healthy controls. Baseline characteristics are shown in the Table. The level of activated FXII did not differ between APS patients and healthy controls (p=0.55) (Figure). 40 APS patients were using anticoagulants. Anticoagulant use was not associated with activated FXII (p=0.25). As expected, patients on anticoagulants had lower thrombin and FIX activation. The subgroup of patients not using anticoagulants did not have elevated thrombin and FIX activation compared to controls.

Conclusion(s): This study shows that, during steady state, there is no difference in FXII activation between APS patients and healthy controls. At group level, APS patients without recent thrombosis do not have significantly increased contact activation pathway activity.