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

Venous thromboembolism (VTE) can recur shortly after stopping anticoagulation, highlighting the need for reliable biomarkers to identify high-risk patients during treatment. To determine whether platelet and endothelial markers predict VTE recurrence. 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 (VKA) for six months. After treatment cessation, patients were followed for two years to assess recurrence. This dataset formed the basis for the current prospective analysis, in which plasma levels of 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. Plasma samples from 629 patients with a first unprovoked VTE who discontinued VKA were analyzed. Recurrence occurred in 75 patients (12%); 11 (15%) within one month, 29 (39%) within three 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: HR: 1.03, 95%CI: 1.01-1.06; aVWF: HR: 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 by sex showed VWF and aVWF were associated with increased recurrence risk in men, but not in women. Elevated levels of VWF and aVWF during anticoagulation were associated with early recurrence in men and might serve as biomarkers for predicting VTE recurrence.