High Levels of von Willebrand Factor and Low Levels of its Cleaving Protease, ADAMTS13, are Associated with Stroke in Young HIV-Infected Patients

Abstract

Background Stroke associated with human immunodeficiency virus infection may occur through a variety of mechanisms. Von Willebrand factor is a marker of endothelial dysfunction, and is elevated in human immunodeficiency virus infection. High levels of von Willebrand factor, a protein involved in platelet adhesion and aggregation, and low levels of ADAMTS13, a metalloproteinase that cleaves von Willebrand factor, have been associated with an increased risk of thrombosis. Aim To investigate the role of von Willebrand factor and ADAMTS13 in the pathogenesis of human immunodeficiency virus-related stroke in young patients. Methods A case-control study ( n = 100) comprising three participant groups: human immunodeficiency virus-positive antiretroviral therapy-naïve young strokes ( n = 20), human immunodeficiency virus-negative young strokes ( n = 40), and human immunodeficiency virus-positive antiretroviral therapy-naïve nonstroke controls ( n = 40). von Willebrand factor and ADAMTS13 levels were measured in plasma samples collected five- to seven-days poststroke. Results Human immunodeficiency virus-positive stroke participants had higher von Willebrand factor levels than human immunodeficiency virus-negative strokes (173·5% vs. 135%, P = 0·032). They tended to have higher levels of von Willebrand factor than human immunodeficiency virus-positive nonstroke controls (173·5% vs. 129%, P = 0·061). Human immunodeficiency virus-positive stroke participants had lower levels of ADAMTS13 than human immunodeficiency virus-positive nonstroke controls (0% vs. 23·5% P = 0·018) most likely due to the effect of the acute stroke. However, in the nonstroke group, these levels were significantly reduced compared with population norms. von Willebrand factor levels in all human immunodeficiency virus-positive participants were negatively correlated with CD4 counts. Conclusions Stroke in human immunodeficiency virus infection is associated with a prothrombotic state, characterized by elevated von Willebrand factor and low ADAMTS13 levels.