Exploratory assessment of bleeding risk associated with concurrent use of Anti-VEGF agents and anticoagulants in oncology.

Background: The concurrent use of anti-vascular endothelial growth factor (VEGF) agents and anticoagulants has become increasingly unavoidable in oncology, while the associated bleeding risk remains poorly characterized. Methods: A retrospective analysis combined with pharmacovigilance assessment was conducted to assess the associated bleeding risk. Patients who received concurrent use of anti-VEGF agents and anticoagulants at Hunan Cancer Hospital between 1 January 2010, and 1 October 2025, were included. Data on demographics, safety and duration of co-administration were collected. Additionally, drug-drug interaction signals were analyzed using FDA Adverse Event Reporting System (FAERS) (Q1, 2013 - Q4, 2024) via Ω shrinkage measure. Results: Among 208 patients (83 on TKIs, 125 on Bev), 32.53% of TKI users and 41.6% of Bev users received anticoagulants for VTE treatment. In the TKI/Bev VTE treatment groups, 51.85% and 61.54% of patients were administered prophylactic anticoagulants, respectively. Rivaroxaban was the primary anticoagulant, followed by low molecular weight heparin (LMWH). For TKIs, the median co-administration duration was 4 days in the prophylaxis group and 30 days in the treatment group, whereas for Bev, the corresponding duration was 28.5 days and 50 days, respectively. Bleeding events were rare across all groups (<6%), with no grade ≥3 events observed. In FAERS, only a potential bleeding signal was observed for Bev-LMWH co-administration (Ω Conclusion: TKI-DOAC/LMWH and Bev-DOAC co-administration appeared to be safe, especially with short-term, prophylactic anticoagulant dosage. Given a potential bleeding signal, Bev-LMWH co-administration requires rigorous clinical monitoring. Owing to the hypothesis-generating nature of our study, definitive safety or causality require prospective validation.