title: Platelet activation rather than endothelial injury identifies risk of thrombosis in subjects positive for antiphospholipid antibodies.
abstract: BACKGROUND
  Anti-phospholipid antibodies (APLA) are often associated with thrombosis, defining the antiphospholipid syndrome (APS) but it remains unclear why many subjects who are positive for APLA chiefly anti-cardiolipin (aCL) or anti-beta2GPI (abeta2GPI) do not develop thrombosis. A related question addressed in this study is whether the target of cellular injury in APS is predominately platelets or endothelial cells (EC).
  
  
  METHODS
  aCL and abeta2GPI were determined by ELISA in 88 patients, 60 of whom were thrombotic and 28 non-thrombotic. Platelet activation was measured by CD62P and by concentration of platelet microparticles (PMP) and EC activation was assessed by endothelial microparticles (EMP), both by flow cytometry. Lupus anticoagulant (LAC) was measured in the hospital laboratory.
  
  
  RESULTS
  There was no difference in frequency of aCL or abeta2GPI, neither IgG or IgM, between the thrombotic and non-thrombotic groups. Both groups showed elevated EMP compared to controls but this did not differ between thrombotic and non-thrombotic groups. In contrast, PMP were not significantly elevated in non-thrombotic but were elevated in thrombotic compared to non-thrombotic (p=0.03) and controls. CD62P, an independent marker of platelet activation, was also elevated in thrombotic vs. non-thrombotic. There was a trend for increased LAC in the thrombotic group but not significant.
  
  
  CONCLUSIONS
  Although all subjects had evidence of endothelial activation, only platelet activation differed between thrombotic and non-thrombotic. This supports the hypothesis that platelet activation predisposes to thrombosis in the presence of chronic EC activation. These data also raise the possibility of distinguishing risk-prone APLA-positive individuals.
authors.affiliation: The Wallace H. Coulter Platelet Laboratory, University of Miami / Miller School of Medicine, 1600 NW 10th Ave, Mail Code R-36A, Miami, FL, 33136, USA. wjy@med.miami.edu
authors.forename: Wenche
authors.initials: W
authors.lastname: Jy
authors.forename: Maike
authors.initials: M
authors.lastname: Tiede
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Bidot
authors.forename: Lawrence L
authors.initials: LL
authors.lastname: Horstman
authors.forename: Joaquin J
authors.initials: JJ
authors.lastname: Jimenez
authors.forename: Julio
authors.initials: J
authors.lastname: Chirinos
authors.forename: Yeon S
authors.initials: YS
authors.lastname: Ahn
mesh_terms: D000328:Adult; D017153:Antibodies, Anticardiolipin / Q000097:blood; D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000209:etiology / Q000276:immunology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000293:injuries*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D012307:Risk Factors; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000276:immunology; D053482:beta 2-Glycoprotein I / Q000276:immunology
chemical_list: D017153:Antibodies, Anticardiolipin; D017152:Antibodies, Antiphospholipid; D019007:P-Selectin; D053482:beta 2-Glycoprotein I