Atherothrombosis in von Willebrand Disease: An Analysis of the Literature and Implications for Clinical Management

Abstract
In spite of coagulation impairment, people with congenital bleeding disorders can still develop atherosclerosis and its thrombotic complications. This issue has been particularly addressed in recent years as an increasing number of such patients now reach an elderly age and have to confront age-related comorbidities, including cardiovascular diseases, and as a consequence, challenges concerning the management of concomitant bleeding and atherothrombotic risk. Von Willebrand disease (VWD), caused by quantitative and/or functional defects of von Willebrand factor (VWF), is the most common congenital bleeding disorder, with an estimated prevalence in the general population of 1 to 2%, although clinically significant VWD is much less common. Despite the high population impact of VWD and increasing knowledge of the pathophysiological role of VWF in atherothrombosis, data concerning atherosclerosis and its vascular complications in VWD patients are rather limited, and even more scarce when clinical management is considered. The relevance of this association is certainly underestimated and, possibly, contributes to bleeding complications observed in patients on antithrombotic treatment or undergoing invasive cardiovascular procedures. This review will analyze the available literature data and discuss the implications for management of VWD patients with atherothrombosis, in the light of the information of bleeding risk in the general population and of recent, growing data from hemophilia patients.