Elevated levels of (active) von Willebrand Factor during anticoagulation are associated with early recurrence of venous thromboembolism

Background: Venous thromboembolism (VTE) can recur shortly after stopping anticoagulation, highlighting the need for reliable biomarkers to identify high-risk patients during treatment. Objectives: To determine whether platelet and endothelial markers predict VTE recurrence. Methods: We used data and samples from the randomized controlled VISTA trial (2011-2015), which included patients with unprovoked VTE who were treated with vitamin K antagonists for 6 months. After treatment cessation, patients were followed for 2 years to assess recurrence. This dataset formed the basis for the current prospective analysis, in which plasma levels of von Willebrand factor (VWF), active VWF (aVWF), soluble P-selectin, soluble thrombomodulin, CXCL4, and CXCL7 were measured before and after cessation of anticoagulation. Associations between biomarker levels and recurrence were analyzed using Cox regression. Results: Plasma samples from 629 patients with a first unprovoked VTE who discontinued vitamin K antagonists were analyzed. Recurrence occurred in 75 patients (12%); 11 (15%) within 1 month, 29 (39%) within 3 months, and 46 (61%) after 3 months. Elevated levels of VWF and aVWF were associated with an increased risk of recurrence per 10-unit increase (VWF: hazard ratio, 1.03; 95% CI, 1.01-1.06; aVWF: hazard ratio, 1.02; 95% CI, 1.00-1.05). Associations were stronger for early recurrence (<3 months), while (a)VWF levels were not associated with late recurrence (>3 months). Stratification showed that VWF and aVWF were associated with increased recurrence risk in men, but not in women. Conclusion: Elevated levels of VWF and aVWF during anticoagulation were associated with early recurrence in men and might serve as biomarkers for predicting VTE recurrence.