Abstract Number: LPB0092
Meeting: ISTH 2021 Congress
Theme: Venous Thromboembolism » VTE Epidemiology
Background: Diverse studies have demonstrated non-haemostatic effects of factor Xa (FXa) inhibition.
Aims: To evaluate whether use of FXa inhibitors alters the concentration of circulating plasma proteins in patients with venous thromboembolism (VTE) in the acute phase and after 12 months of follow-up, compared to individuals not treated with anticoagulants before blood sampling.
Methods: Circulating levels of 444 proteins were measured by proximity extension assay in the acute setting of VTE (baseline) in 147 individuals treated with FXa inhibitors and in 89 individuals not receiving anticoagulants recruited in the GMP-VTE project, a multi-center, prospective cohort study on VTE. At the 12-month follow-up evaluation, plasma samples of 103 individuals treated with FXa inhibitors and 59 individuals not treated with anticoagulants were analyzed. LASSO-regularized logistic regression was used to identify plasma proteins altered by FXa inhibitors at both time points. Multivariable linear regression was used to assess the association of identified proteins with coagulation tests, and age and sex-adjusted proportional hazards Cox regression was performed to test their associations with clinical outcome over 2 years of follow-up.
Results: At baseline, 19 proteins were identified as altered by FXa inhibition. At the 12-month follow-up examination, 6 proteins with altered levels were identified. The candidate proteins showed moderate procoagulant or anticoagulant effects as assessed with coagulation tests. Fibroblast growth factor-19 (Hazard ratio [HR]:0.56, 95% Confidence Interval [CI]: 0.36-0.87), Brother of CDO (HR:1.76, 95%CI:1.10-2.81) and granulysin (HR:1.75, 95%CI:1.26-2.45) concentrations were age and sex-independently associated with thromboembolic events or death. For clinically relevant bleeding, an age and sex independent association was found for tumour necrosis factor receptor–associated factor family member-associated NF-κB activator (HR:1.59, 95%CI: 1.05-2.41) only.
Conclusions: This investigation has identified candidate proteins related to FXa inhibition that are not directly related to coagulation, providing new insights into non-haemostatic mechanisms of action of FXa inhibitors in the setting of VTE.
To cite this abstract in AMA style:
Pallares Robles A, ten Cate V, Schulz A, H Prochaska J, Rapp S, Köck T, Heitmeier S, Schwers S, Leineweber K, Ghofrani HA, Meyer FJ, Espinola-Klein C, Lackner KJ, Münzel T, Konstantinides SV, Wild PS. Alteration of the Circulating Plasma Proteome by FXa Inhibition in Venous Thromboembolism and the Relationship with Clinical Outcome [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/alteration-of-the-circulating-plasma-proteome-by-fxa-inhibition-in-venous-thromboembolism-and-the-relationship-with-clinical-outcome/. Accessed March 22, 2024.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/alteration-of-the-circulating-plasma-proteome-by-fxa-inhibition-in-venous-thromboembolism-and-the-relationship-with-clinical-outcome/