Elevated von Willebrand factor levels during anticoagulation predict early recurrence of venous thromboembolism

Introduction: Recurrence of venous thromboembolism (VTE) is an important concern when deciding to (dis)continue anticoagulation. Since recurrence can occur shortly after discontinuation, there is a need for reliable biomarkers to identify high-risk patients while still on anticoagulation. This study aims to determine whether von Willebrand factor (VWF) levels can predict (early) VTE recurrence.

Method: We utilized data and samples from the VISTA trial, which included patients with unprovoked venous thromboembolism (VTE) treated with vitamin K antagonists (VKA) for six months. Patients were then randomized to either continue or discontinue VKA based on their recurrence risk assessed by the Vienna Prediction Model (intervention arm) or receive usual care (control arm). The follow-up period lasted two years. Plasma levels of von Willebrand factor (VWF) and its active conformation (aVWF) were measured during anticoagulation. Associations between VWF levels and recurrence were evaluated using cox regression.

Results: Plasma samples from 629 patients with a first unprovoked VTE who discontinued VKA were analyzed. Recurrence occurred in 75 patients (12%), with 11 (15%) recurrences within one month and 29 (39%) within three months after VKA discontinuation. Elevated levels of VWF and aVWF were associated with an increased risk of recurrence (VWF: HR: 1.03, 95% CI: 1.01-1.06; aVWF: HR: 1.02, 95% CI: 1.00-1.05). Kaplan-Meier curves showed that patients in the highest tertile of VWF and aVWF had more recurrences compared to those in the lower tertiles ([Fig. 1]). The associations with early recurrence (<30 days) were stronger (VWF: HR: 1.08, 95% CI: 1.02-1.13; aVWF: HR: 1.06, 95% CI: 1.03-1.09), while VWF and aVWF levels were not associated with late recurrence (>90 days) (VWF: HR: 1.01, 95% CI: 0.97-1.05; aVWF: HR: 1.00, 95% CI: 0.96-1.04). Stratification by sex revealed that plasma levels of VWF and aVWF were associated with increased recurrence risk in men (VWF: HR: 1.04, 95% CI: 1.01-1.06; aVWF: HR: 1.02, 95% CI: 1.00-1.04) but not in women (VWF: HR: 0.98, 95% CI: 0.92-1.05; aVWF: HR: 0.99, 95% CI: 0.91-1.07).

Fig. 1 Kaplan-Meier Curves for Recurrence-Free Survival by Biomarker Tertile Kaplan-Meier curves illustrating recurrence-free survival stratified by tertiles of biomarker levels. X-axis: Follow-up in days; Y-axis: Percentage of patients remaining recurrence-free. Data represent the survival probabilities of patients at different tertile levels: green; highest tertile, pink; middle tertile, and black; lowest tertile. Censoring events are indicated by a thin line on top of the curves.

Conclusion: Elevated levels of VWF and aVWF during anticoagulation were associated with early recurrence of VTE in men, but not in women. These findings suggest that VWF and aVWF may serve as valuable biomarkers for identifying high-risk patients who could benefit from continued anticoagulation.

Publikationsverlauf

Artikel online veröffentlicht:
13. Februar 2025