Diabetes mellitus (DM) is one of the most important risk factors for Peripheral Arterial Disease (PAD) and is the leading cause of non-traumatic lower limb amputation as a consequence of diabetic foot vasculopathy. PAD evolves into chronic limb-threatening ischemia (CLTI) over time, typically requiring lower limb revascularization procedures such as Percutaneous Transluminal Angioplasty (PTA).1 Interestingly, subjects with DM have a higher incidence of re-stenosis after lower limb PTA compared to subjects without DM.

As emerged from the COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial, DM subjects with PAD have a higher risk to develop major adverse limb events (MALEs defined as severe limb ischemia leading to surgery or major vascular amputation). Of a total of 6391 subjects with PAD, 128 individuals developed MALEs of whom 69 subjects (53.9 %) were affected by DM.2,3

The pathophysiological mechanisms involved in the higher incidence of re-stenosis after PTA in DM patients have not been clearly defined. However, recent studies have demonstrated that subjects with DM have a higher risk of re-stenosis after PTA due to an increased risk of thrombotic angiopathies, mediated by altered von Willebrand Factor (VWF) activity, which is involved in primary hemostasis. Nonetheless, studies have suggested that the most important elements of re-stenosis after PTA are the length of the involved arterial segments4 and the number of patent arteries after surgery.5

In physiological conditions, the thrombogenic activity of VWF is directly proportional to its molecular size and inversely related to its proteolysis by ADAMTS-13. ADAMTS-13 is a complex multidomain enzyme which cleaves VWF at the amino acid residues between Tyr1605 and Met1606 in the A2 domain,6., 7., 8., 9. producing smaller VWF multimers. The impairment of ADAMTS-13-mediated VWF cleavage in the before-mentioned positions produces dysfunctional VWF multimers. Interestingly, DM is associated with an increased oxidative stress environment, which produces aberrant VWF oxidation products and impairs ADAMTS-13 activity.10 Indeed, elevated VWF levels and high molecular weight VWF multimers present in subjects with DM have been shown to have a significantly increased risk of developing thrombotic angiopathies.

Therefore, we hypothesize that increased VWF levels and/or the altered interaction between VWF and ADAMTS-13 could affect the outcome of PTA and play a role in the occurrence of re-stenosis in subjects with type 2 diabetes (T2DM), CLTI and diabetic foot vasculopathy.

We compared VWF antigen levels, VWF activity and ADAMT-13 activity in patients who underwent successful PTA with subjects who underwent to a less effective procedure to highlight possible differences. The effectiveness of PTA was monitored through transcutaneous oximetry.