Von Willebrand Factor and ADAMTS13 in Relation to Major Adverse Limb Events in Peripheral Artery Disease

This study aimed to investigate the relationship between the two biomarkers, von Willebrand factor (VWF) and ADAMTS13, and major adverse limb events (MALE) in patients with peripheral artery disease (PAD).

After obtaining informed consent, baseline blood samples were collected from 48 PAD patients aged 60-75 years who were undergoing assessment, surveillance, medical management, or consideration for surgical intervention. VWF and ADAMTS13 antigen levels were measured by enzyme-linked immunosorbent assay (ELISA). Patients were monitored prospectively for subsequent MALE, defined as lower-limb revascularization or major amputation. Biomarker levels were compared between patients who did and did not experience subsequent MALE using Mann-Whitney U-tests, and time to MALE was evaluated using Kaplan-Meier analyses. This study was approved by the Unity Health Toronto Research Ethics Board.

Twenty-four patients (50%) experienced MALE after baseline blood sampling. These patients had significantly lower VWF antigen levels (median [interquartile range]: 17,817.18 [32,339.16] ng/mL vs. 46,175.95 [75,284.64] ng/mL, P=0.026) and lower VWF/ADAMTS13 ratios (P=0.008) than those without MALE. Kaplan-Meier analyses comparing biomarker values above versus below the cohort median showed non-significant trends toward a higher cumulative incidence of MALE during follow-up for lower VWF, higher ADAMTS13, and lower VWF/ADAMTS13 ratios. In an exploratory analysis excluding patients with baseline chronic limb-threatening ischemia, below-median VWF/ADAMTS13 ratios were associated with a higher cumulative incidence of MALE during follow-up (log-rank P=0.018).

Contrary to our original hypothesis, lower baseline VWF levels and VWF/ADAMTS13 ratios were associated with subsequent MALE in this high-risk PAD cohort, which may reflect increased VWF consumption in severe, diffuse atherosclerosis. This study contributes to the limited literature on VWF and ADAMTS13 in PAD in relation to MALE, as previous research has largely focused on major adverse cardiovascular events. Larger studies in patients with similar risk profiles are required to validate these findings.