title: Poly-N-acetylglucosamine fibers amplify the effectiveness of recombinant factor VIIA on clot formation in hemophilia B canine blood.
abstract: BACKGROUND
  Achieving hemostasis in anticoagulated patients is an increasingly important clinical issue. Poly-N-acetylglucosamine (pGlcNAc) nanofibers activate platelets by β3 subunit (CD61) and the von Willebrand receptor GP1b (CD42b) integrin signaling for generation of a prothrombotic surface membrane. Recombinant coagulation factor VIIa (rFVIIa) functions in hemophilia A and B by catalyzing formation of the Xa/Va complex on the surface of activated platelets. These observations suggest that pGlcNAc nanofibers may amplify the activity of rFVIIa in hemophilic blood.
  
  
  METHODS
  The activity of rFVIIa on platelets was tested by performing thromboelastographic analysis with blood from hemophilia B dogs in the presence of pGlcNAc nanofibers and increasing concentrations of rFVIIa. Mechanisms for hemostatic system activation were investigated with inhibitors of tissue factor, factor XIIa, and platelet function.
  
  
  RESULTS
  Recombinant FVIIa was observed to partially restore the ability of the hemophiliac blood to form fibrin clots in a dose-dependent manner with thromboelastographic analysis. The addition of pGlcNAc nanofibers amplified the rFVIIa effect. The activity of rFVIIa and the amplification effect of pGlcNAc were dependent on platelet integrin function but independent of FXIIa and tissue factor activities.
  
  
  CONCLUSIONS
  The pGlcNAc nanofibers amplify rFVIIa activity in hemophilia B canine blood by activating platelets through integrin-dependent mechanisms.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27516, USA. tfischer@med.unc.edu
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Fischer
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Nichols
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Scull
authors.forename: Carr J
authors.initials: CJ
authors.lastname: Smith
authors.forename: Marina
authors.initials: M
authors.lastname: Demcheva
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D004285:Dogs; D015942:Factor VIIa / Q000494:pharmacology*; D002836:Hemophilia B / Q000097:blood* / Q000188:drug therapy; D057139:Nanofibers; D015539:Platelet Activation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D013916:Thrombelastography
chemical_list: D011994:Recombinant Proteins; C113831:poly-N-acetyl glucosamine; C103587:recombinant FVIIa; D015942:Factor VIIa; D000117:Acetylglucosamine