# Intrinsic pathway activation in patients with antiphospholipid syndrome and healthy controls

## TL;DR

This study found no significant intrinsic pathway activation in APS patients compared to healthy controls, suggesting it may not be a key factor in APS outside of thrombotic events.

## Contribution

The study provides new evidence on intrinsic pathway activation in APS patients not experiencing recent thrombotic or obstetric events.

## Key findings

- APS patients showed no significant difference in FXII activation compared to healthy controls.
- Activation of FXI and FIX also did not differ between APS patients and controls.
- APS patients on anticoagulants showed no difference in FXII and FXI activation.

## Abstract

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.

To compare in vivo intrinsic pathway activation of patients with APS and healthy controls.

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.

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.

Intrinsic pathway activation in patients with APS without recent thrombotic or obstetric events did not differ significantly compared with healthy controls.

•Patients with thrombotic antiphospholipid syndrome (APS) respond poorly to direct oral anticoagulants.•Inhibitors against intrinsic pathway factors XI and XII are in development.•A cohort study assessed intrinsic pathway activation in patients with APS and healthy controls.•Outside of thrombotic episodes, patients with APS show no increased intrinsic pathway activation.

Patients with thrombotic antiphospholipid syndrome (APS) respond poorly to direct oral anticoagulants.

Inhibitors against intrinsic pathway factors XI and XII are in development.

A cohort study assessed intrinsic pathway activation in patients with APS and healthy controls.

Outside of thrombotic episodes, patients with APS show no increased intrinsic pathway activation.