Biomarkers of increased bleeding risk in patients with atrial fibrillation on oral anticoagulation: a narrative review.

Background and Objective: Atrial fibrillation (AF) is an independent risk factor for ischemic stroke and systemic thromboembolism. Oral anticoagulation (OAC) effectively reduces stroke risk but also increases bleeding risk. Current clinical risk scores for bleeding in AF patients have only modest predictive ability and overlapping stroke and bleeding risk factors complicate treatment decisions. This narrative review aims to review and evaluate current evidence on biomarkers that can predict bleeding risk in AF patients on OAC and assess their integration into risk-scoring systems to guide more personalised clinical decision-making. Methods: This narrative review summarises data from major clinical trials and cohort studies evaluating bleeding-related biomarkers in AF patients on OAC, including growth differentiation factor 15 (GDF-15), high-sensitivity cardiac troponin (hs-cTn), N-terminal prohormone-brain natriuretic peptide (NT-pro-BNP), interleukin-6 (IL-6), von Willebrand factor (vWF), cystatin C, and D-dimer. The prognostic value of these biomarkers, their role in risk scores (e.g., ABC-bleeding), and their ability to improve predictive accuracy were examined. Key Content and Findings: In recent years, several biomarkers have shown promise in predicting bleeding risk in patients with AF on OAC. GDF-15 has consistently emerged as a strong independent marker of significant bleeding and mortality, validated in trials such as Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY), Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE), and Edoxaban Versus Warfarin in Patients with Atrial Fibrillation trial (ENGAGE AF-TIMI 48). hs-cTn and D-dimer levels are also independently associated with an increased bleeding risk and have been included in the ABC-bleeding score, which has shown superior predictive ability compared to traditional scores, such as HAS-BLED. Biomarkers such as cystatin C, which reflects renal dysfunction, vWF, and IL-6 have demonstrated associations with adverse outcomes, although their predictive abilities vary. The inclusion of these biomarkers in clinical tools has improved bleeding risk prediction. Although trials and cost-effectiveness models suggest clinical benefit, further real-world validation is required to confirm their place in everyday clinical practice. Conclusions: Several biomarkers have demonstrated the ability to predict bleeding risk in patients with AF. Risk-scoring systems that incorporate biomarkers have improved the prediction of bleeding events. More accurate identification of patients at higher risk of bleeding allows clinicians and patients to better balance the risks of bleeding versus stroke in the setting of AF and create individualised care plans to lower the overall rate of both stroke and bleeding.