title: ADAMTS13 activity and the presence of acquired inhibitors in human immunodeficiency virus-related thrombotic thrombocytopenic purpura.
abstract: BACKGROUND
  Little is known about the pathophysiology of human immunodeficiency virus (HIV)-related thrombotic thrombocytopenic purpura (TTP). It is generally assumed that acquired ADAMTS13 deficiency is due to the presence of autoantibody inhibitors, but limited data are available regarding ADAMTS13 activity and inhibitors in such patients.
  
  
  METHODS
  By use of a collagen-binding assay, ADAMTS13 activity was analyzed at presentation in 20 patients with HIV-related TTP. The presence of inhibitors in patients with reduced ADAMTS13 activity was assessed with mixing studies. The correlation between ADAMTS13 activity and inhibitors and other laboratory and clinical parameters was assessed.
  
  
  RESULTS
  The patients fell clearly into two groups with regard to ADAMTS13 activity. Six patients (30%) had activity within the normal range, whereas the remaining 14 patients had severely reduced levels. Of the patients with reduced activity, only 5 patients had a detectable inhibitor whereas 8 showed no evidence of an inhibitor. There was significant correlation between normal ADAMTS13 activity and lower CD4 counts (p = 0.049). von Willebrand factor (VWF) antigen levels were significantly higher in patients with reduced ADAMTS13 activity (p = 0.03). Low activity in the absence of a detectable inhibitor was associated with significantly higher D-dimer levels (p = 0.01) and worse clinical outcome.
  
  
  CONCLUSIONS
  The heterogeneity with regard to ADAMTS13 activity and the absence of inhibitors in the majority of patients indicate that other factors are important in the pathogenesis of HIV-related TTP. VWF release and localized coagulation activation due to direct viral or cytokine-mediated endothelial cell injury is likely to be playing a major role.
authors.affiliation: Department of Haematology and Molecular Medicine and the Epidemiology Data Center, University of the Witwatersrand, Johannesburg, South Africa. kareng@thasululo.co.za
authors.forename: Karen
authors.initials: K
authors.lastname: Gunther
authors.forename: Dominique
authors.initials: D
authors.lastname: Garizio
authors.forename: Paul
authors.initials: P
authors.lastname: Nesara
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D011480:Protease Inhibitors / Q000627:therapeutic use; D011697:Purpura, Thrombotic Thrombocytopenic / Q000188:drug therapy* / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D011480:Protease Inhibitors; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human