The imbalance between von Willebrand factor and ADAMTS13 and the risk of venous thromboembolism

Background: ADAMTS13 has a pivotal role in hemostasis since it cleaves the unusually large (UL) von Willebrand factor (VWF) multimers into less prothrombotic molecules. Our objective was to investigate in a case-control study the effect of VWF and ADAMTS13 antigen levels on venous thromboembolism (VTE) risk. Methods: The study included 76 patients of both genders, aged between 18–70 years, with a first episode of deep vein thrombosis (DVT) of the leg and/or pulmonary embolism (PE), and 96 controls without VTE. Blood was collected ≥6 months after VTE. To define high levels of VWF antigen (VWF:Ag) (>150%) and low levels of ADAMTS13 antigen (≤0.64 µg/mL), we used the 88th and 10th percentiles of controls, respectively. Results: Median ADAMTS13 was lower in the group with high VWF:Ag as compared to the group with VWF:Ag levels ≤88th percentile, in patients (0.75 versus 0.95 µg/mL, P=0.001) and in controls (0.80 versus 0.98 µg/mL, P=0.051). The combination of high VWF:Ag and low ADAMTS13 levels was found in 8 patients and 3 controls, yielding an odds ratio (OR) adjusted for age, gender, ABO blood group and C-reactive protein (CRP) of 4.20 [95% confidence interval (CI): 1.02–17.32] when compared to neither exposure (52 patients and 79 controls). Risk estimates were attenuated when further adjusted for high levels of factor VIII (FVIII; OR 3.39, 95% CI: 0.79–14.55). Conclusions: Our data suggest an association of high VWF:Ag and low ADAMTS13 antigen levels with VTE. Further studies are warranted to clarify the potential effect of the VWF-ADAMTS13 axis on VTE risk.