Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation

Abstract

Background: Oral anticoagulants (OAC) in patients with atrial fibrillation (AF) prevent thromboembolic events, but are associated with significant risk of bleeding. Objectives:To explore associations between a wide range of biomarkers and bleeding risk in patients with AF on OAC.Method: Biomarkers were analyzed in a random sample of 4200 patients, 204 cases with major bleedings, from ARISTOTLE. The replication cohort included 344 cases with major bleeding and 1024 random controls from RE-LY. Plasma samples obtained at randomization were analyzed by the Olink Proximity Extension Assay cardiovascular and inflammation panels and conventional immunoassays. The associations between biomarker levels and major bleeding over 1 to 3 years of follow-up were evaluated by random survival forest/Boruta analyses and Cox regression analyses to assess linear associations and hazard ratios for identified biomarkers.Results: Out of 268 proteins, nine biomarkers were independently associated with bleeding in both cohorts. In the replication cohort the linear hazard ratios (95% confidence intervals) per interquartile range were for these biomarkers: TNF-R1 1.748

Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation: Comment from Luo et al.

“…Thus, it is unclear whether the strong correlation between the increased level of TRAIL‐R2 and the risk of bleeding uncovered in Agneta Siegbahn's study is confounded by other unknown factors. We speculate that the potential mechanism is that TRAIL‐R2 induces the inflammatory activity of cells, leading to inflammatory injury of endothelial cells and apoptosis of the vascular wall 1,5 . Taken together, we can reasonably speculate that TRAIL‐R2 may be a biomarker and contribute to predicting future cardiovascular events in AF patients by affecting the risk of bleeding.…”

“…We speculate that the potential mechanism is that TRAIL-R2 induces the inflammatory activity of cells, leading to inflammatory injury of endothelial cells and apoptosis of the vascular wall. 1,5 Taken together, we can reasonably speculate that TRAIL-R2 may be a biomarker and contribute to predicting future cardiovascular events in AF patients by affecting the risk of bleeding. Clearly, a great number of research opportunities could be further explored following Agneta Siegbahn's interesting study.Despite some limitations, the work by authors not only provides novel candidate biomarkers associated with major bleeding for AF but also opens a new avenue to future basic and clinical studies in AF.…”

“…It was with great interest that we read the study entitled “Multiplex protein screening of biomarkers associated with major bleeding in patients with atrial fibrillation treated with oral anticoagulation” by Agneta Siegbahn and colleagues published in The Journal of Journal of Thrombosis and Haemostasis in August 2021 1 …”

“…In this interesting paper, the authors revealed that nine out of 268 investigated biomarkers were significantly and independently associated with the risk of bleeding and reflect pathophysiologic processes of inflammation, apoptosis, oxidative stress, vascular calcification, coagulation, and fibrinolysis 1 . Recent studies have shown that accurate assessment to balance the risk of stroke and systemic embolic events, against the risk of major bleeding is, therefore, an important therapeutic goal in the clinical management of atrial fibrillation (AF) patients 2 .…”

Elucidation of Cellular Contributions to Heparin-Induced Thrombocytopenia Using Omic Approaches

“…Another recent study showed substantive changes to expression of focal adhesion and cytoskeletal proteins in podocytes following chronic heparin exposure (Delézay et al, 2021). In a cohort of 4,200 oral anticoagulant patients with atrial fibrillation, one recent study identified seven novel proteins associated with increased risk of bleeding (Siegbahn et al, 2021). A number of other targeted proteomic studies have reported additional biomarkers associated with risk of bleeding in patients with acute coronary syndromes (Hagström et al, 2016;Hijazi et al, 2016).…”