title: Heparin immobilization reduces thrombogenicity of small-caliber expanded polytetrafluoroethylene grafts.
abstract: OBJECTIVE
  The patency of small-diameter expanded polytetrafluoroethylene (ePTFE) grafts for vascular reconstruction is impaired by acute thrombotic occlusion. Prosthetic materials are thrombogenic and cause platelet adhesion and activation of the coagulation cascade. Heparin is a potent anticoagulant drug widely used to prevent and treat thrombosis. A new ePTFE graft with long-term bonding of heparin is now commercially available in several European countries, but a basic analysis of its mechanism of action in humans has never been performed. This study was performed to evaluate the thrombogenicity of heparin-bonded ePTFE grafts compared with standard ePTFE in a newly developed human ex vivo model.
  
  
  METHODS
  Nonanticoagulated blood was drawn from antecubital veins of 10 healthy donors with a 19-gauge needle. The proximal end of a 60-cm ePTFE vascular graft with a diameter of 3 mm was connected to the needle while the distal end was connected to a syringe, which was placed in a syringe pump. Every volunteer served as his or her own control by using a heparin-bonded ePTFE graft on one arm and a standard ePTFE graft on the other arm. The perfusions were performed over 6 minutes with a flow rate of 20 mL/min, corresponding to a shear rate of 74/s. Serial samples were taken at the distal end of the graft for determination of prothrombin fragment 1 + 2, fibrinopeptide A, and P-selectin expression on perfused platelets. Fibrin deposition and platelet deposition were studied by using scanning electronic microscopy.
  
  
  RESULTS
  Fibrinopeptide A production over time was significantly reduced on the heparin-bonded ePTFE grafts compared with standard ePTFE grafts (P < .05). There was no increase in the production of prothrombin fragment 1 + 2 or P selectin over time on either type of graft. Scanning electronic microscopy scanning showed platelet deposition and fibrin formation on standard ePTFE grafts, whereas no platelets or fibrin were observed on heparin-bonded ePTFE grafts.
  
  
  CONCLUSIONS
  Heparin immobilization substantially reduces the thrombogenicity of small-diameter ePTFE in a newly developed human ex vivo model. In this study, we provide evidence that the mechanism of action of the heparin bonding is due not only to anticoagulant but also to antiplatelet effects. Heparin bonding may be an important improvement of ePTFE, resulting in better patency rates for vascular reconstructions.
authors.affiliation: Department of Vascular Surgery, University Medical Center, Utrecht, The Netherlands.
authors.forename: Jan M M
authors.initials: JM
authors.lastname: Heyligers
authors.forename: Hence J M
authors.initials: HJ
authors.lastname: Verhagen
authors.forename: Joris I
authors.initials: JI
authors.lastname: Rotmans
authors.forename: Cees
authors.initials: C
authors.lastname: Weeterings
authors.forename: Philip G
authors.initials: PG
authors.lastname: de Groot
authors.forename: Frans L
authors.initials: FL
authors.lastname: Moll
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
mesh_terms: D001807:Blood Vessel Prosthesis / Q000009:adverse effects*; D005337:Fibrin / Q000032:analysis; D005344:Fibrinopeptide A / Q000032:analysis; D006493:Heparin / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019007:P-Selectin / Q000032:analysis; D010446:Peptide Fragments / Q000032:analysis; D010973:Platelet Adhesiveness / Q000187:drug effects; D011138:Polytetrafluoroethylene / Q000009:adverse effects*; D011516:Prothrombin / Q000032:analysis; D013927:Thrombosis / Q000517:prevention & control*
chemical_list: D019007:P-Selectin; D010446:Peptide Fragments; C045879:prothrombin fragment 1.2; D005344:Fibrinopeptide A; D011516:Prothrombin; D005337:Fibrin; D011138:Polytetrafluoroethylene; D006493:Heparin