Plasma proteomics does not identify biomarkers of venous thromboembolism recurrence during and after anticoagulation: results from the VISTA study

Background Venous thromboembolism (VTE) is typically treated with anticoagulation for 3 to 6 months. Decisions about extending treatment require balancing recurrence and bleeding risk. Current prediction models based on clinical markers lack sufficient discriminative accuracy, emphasizing the need for reliable biomarkers. Objectives To identify plasma biomarkers associated with VTE recurrence during and after anticoagulation. Methods We conducted a case-cohort study using data and samples from the VISTA trial, which followed patients with a first VTE who were treated with vitamin K antagonists (VKAs) for 6 months. Follow-up for recurrence was 2 years. Recurrence cases ( N = 96) were compared with a randomly selected subcohort ( n = 192). Plasma was collected in the final month of VKA therapy and 1 month after cessation. Unbiased mass spectrometry-based proteomics was used to analyze plasma proteins. Results Principal component analysis revealed no global proteomic differences between patients with and without recurrence. In addition, no statistically significant changes in plasma protein levels were associated with recurrence, neither during nor after treatment. While paired sampling demonstrated variability in interindividual responses upon initiation and cessation of VKA treatment, including VKA-dependent coagulation proteins (eg, prothrombin [factor {F}II], coagulation FVII, FXI, FX, vitamin K-dependent protein S, protein C, and protein Z), there were no statistically significant differences in protein-level alterations associated with recurrence. Conclusion While plasma proteomics captured anticoagulation effects, it did not reveal biomarkers predictive of VTE recurrence, underscoring the need for alternative approaches.