title: Low concentration detergent sclerosants induce platelet activation but inhibit aggregation due to suppression of GPIIb/IIIa activation in vitro.
abstract: BACKGROUND
  Sclerotherapy is associated with thromboembolic and ischemic neurological adverse events but the effects of sclerosants on platelet function are unknown. The aim of this study was to investigate the in vitro effects of detergent sclerosants Sodium Tetradecyl Sulphate (STS) and Polidocanol (POL) on platelet activation and aggregation.
  
  
  METHODS
  Whole blood and platelet rich plasma samples were incubated with sclerosants. Platelet and platelet microparticle (PMP) counts were measured by flow cytometry. Platelet activation was examined by ELISA for soluble factors (sP-selectin, von Willebrand factor, sCD40L and serotonin) and by flow cytometry for membrane-bound markers (CD62p, CD63) and cytoplasmic calcium. Platelet aggregation was assessed by PFA-100®, light transmission and impedance (Multiplate®) aggregometry, and by flow cytometry for glycoprotein (GP) Ib and GPIIb/IIIa subunits, heterodimer expression and activation (PAC-1 binding).
  
  
  RESULTS
  Both agents lysed platelets at high concentrations (≥ 0.1%) but induced platelet activation at lower concentrations as evident by a rise in membrane-bound and soluble markers, cytoplasmic calcium and release of phosphatidylserine+PMP. Agonist-stimulated platelet aggregation was inhibited by both sclerosants. Membrane expression of GPIb and GPIIb/IIIa individual subunits or heterodimer was not affected by sclerosants but the activation of GPIIb/IIIa was suppressed.
  
  
  CONCLUSIONS
  Low concentration sclerosants activated platelets and released microparticles but inhibited platelet aggregation due to suppression of GPIIb/IIIa activation.
authors.affiliation: Haematology Research Laboratory, St Vincent's Hospital, Sydney, Australia. kparsi@stvincents.com.au
authors.forename: Kurosh
authors.initials: K
authors.lastname: Parsi
authors.forename: David E
authors.initials: DE
authors.lastname: Connor
authors.forename: Anne
authors.initials: A
authors.lastname: Pilotelle
authors.forename: Joyce
authors.initials: J
authors.lastname: Low
authors.forename: David D F
authors.initials: DD
authors.lastname: Ma
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Joseph
mesh_terms: D002478:Cells, Cultured; D003902:Detergents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012597:Sclerosing Solutions / Q000008:administration & dosage*; D012981:Sodium Tetradecyl Sulfate / Q000008:administration & dosage*
chemical_list: D003902:Detergents; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D012597:Sclerosing Solutions; D000077423:Polidocanol; D011092:Polyethylene Glycols; D012981:Sodium Tetradecyl Sulfate