title: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Division of Neurology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Sameera
authors.initials: S
authors.lastname: Allie
authors.affiliation: Division of Neurology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Alan
authors.initials: A
authors.lastname: Stanley
authors.affiliation: Division of Neurology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Alan
authors.initials: A
authors.lastname: Bryer
authors.affiliation: Department of Haematology and Cell Biology, University of Free State, Bloemfontein, South Africa.
authors.forename: Muriel
authors.initials: M
authors.lastname: Meiring
authors.affiliation: Division of Neurology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.|Division of Geriatric Medicine, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
authors.forename: Marc I
authors.initials: MI
authors.lastname: Combrinck
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000150:complications*; D006801:Humans; D008297:Male; D020521:Stroke / Q000097:blood* / Q000150:complications*; D014841:von Willebrand Factor / Q000032:analysis*
chemical_list: D015415:Biomarkers; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: HIV infection; stroke; von Willebrand factor