Proteomic Biomarkers in VTE: From Discovery to Clinical Translation

Background: Venous thromboembolism (VTE) remains a leading cause of global morbidity and mortality. The pathophysiological mechanisms leading to VTE are still not fully elucidated. Diagnostic biomarkers for VTE lack specificity, and biomarkers to guide the duration of anticoagulation therapy have not yet entered routine clinical practice. Proteomics has emerged as a high-throughput approach for novel biomarker discovery, offering insights into the complex biological processes across the VTE continuum. This review explores current VTE proteomic research and discusses the challenges and gaps hindering clinical translation. Methods: We performed a narrative review based on a search of Scopus and PubMed for original human proteomic studies published between 1995 and July 2025. Results were limited to whole-blood, plasma or serum-based studies. Results: A total of 1190 studies were retrieved, of which 27 studies were included in this review. Studies were mainly plasma-based. Studies compared VTE patients to non-VTE controls, different VTE subtypes, and various provoked VTE cohorts. Broad themes identified proteomic signatures involving dysregulated coagulation, complement activation, inflammation, and platelet activation. Conclusions: Current proteomic evidence supports VTE as a systemic immunothrombotic disorder that shows key differences even years before developing VTE. Proteomic research in VTE holds the promise to identify biomarkers that may aid in the diagnosis and guide management of VTE. However, most proteomic findings remain exploratory to date and methodologies are varied across studies. Future studies should prioritise the workflow standardisation and validate promising biomarker panels in large-scale, prospective, longitudinal cohorts.