title: A heparin-bonded vascular graft generates no systemic effect on markers of hemostasis activation or detectable heparin-induced thrombocytopenia-associated antibodies in humans.
abstract: OBJECTIVE
  Almost a third of patients who undergo peripheral bypass procedures do not have suitable veins, making the use of prosthetic materials necessary. Prosthetic materials can cause platelet adhesion and activation of the coagulation cascade on the graft. One potential strategy to reduce this thrombogenicity is to covalently bind heparin to the endoluminal surface of grafts. This human in vivo study examined systemic effects of the endoluminal heparin and addressed whether graft implantation results in (1) a measurable reduction of systemic markers of hemostasis activation compared with control grafts and (2) antibody formation against heparin, potentially responsible for heparin-induced thrombocytopenia (HIT).
  
  
  METHODS
  The study included 20 patients undergoing femoropopliteal bypass grafting, of whom 10 received a standard Gore-Tex Thin Walled Stretch Vascular Graft (W. L. Gore & Associates, Flagstaff, Ariz) and 10 received a heparin-bonded expanded polytetrafluoroethylene (ePTFE) graft (Gore-Tex Propaten Vascular Graft). Blood samples were drawn before and directly after the operation and at days 1, 3, 5, and week 6 after surgery. Established markers of in vivo activation of platelets and blood coagulation (prothrombin fragment 1+2, fibrinopeptide A, soluble glycoprotein V, thrombin-antithrombin complexes, and D-dimers) were measured using standard commercially available techniques. Antiplatelet factor 4/heparin antibody titers were measured using a commercially available enzyme-linked immunosorbent assay, and platelet counts were determined.
  
  
  RESULTS
  No statistical differences were observed in any of the markers of in vivo activation of platelets and blood coagulation between patients receiving Propaten or control ePTFE. Moreover, no antibodies against heparin could be demonstrated up to 6 weeks after implantation.
  
  
  CONCLUSIONS
  No measurable effect of heparin immobilization on systemic markers of hemostasis was found using a heparin-bonded ePTFE graft in vivo. Also, no antibodies against heparin could be detected up to 6 weeks after implantation.
authors.affiliation: Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands. j.heyligers@elisabeth.nl
authors.forename: Jan M M
authors.initials: JM
authors.lastname: Heyligers
authors.forename: Ton
authors.initials: T
authors.lastname: Lisman
authors.forename: Hence J M
authors.initials: HJ
authors.lastname: Verhagen
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
mesh_terms: D000368:Aged; D000906:Antibodies / Q000097:blood*; D000925:Anticoagulants / Q000009:adverse effects* / Q000276:immunology; D000990:Antithrombin III; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005344:Fibrinopeptide A / Q000378:metabolism; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000503:physiopathology / Q000601:surgery*; D010976:Platelet Count; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D011138:Polytetrafluoroethylene; D011474:Prosthesis Design; D011516:Prothrombin; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D016896:Treatment Outcome; D014654:Vascular Patency
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D019038:Platelet Glycoprotein GPIb-IX Complex; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D005344:Fibrinopeptide A; D000990:Antithrombin III; D011516:Prothrombin; D011138:Polytetrafluoroethylene; D006493:Heparin; D010447:Peptide Hydrolases