title: Heparin-bonded grafts induce platelet aggregation in the presence of heparin-associated antiplatelet antibodies.
abstract: OBJECTIVE
  Thromboresistant synthetic grafts should decrease the frequency of graft thromboses and could be useful in bypasses to small arteries and to arteries with compromised flow. Heparin-bonded grafts (HBG) have been developed. Studies were done to determine whether the heparin bond is permanent and whether the HBG would aggregate platelets in the presence of heparin-associated antiplatelet antibodies (HAAbs).
  
  
  METHODS
  We studied an 8 mm HBG from company A (HBGA) and 8 mm and 6 mm HBGs from company B (HBGB-8 and HBGB-6), none of which is available for clinical use in the United States. Five 1 cm long segments of HBGA, HBGB-8, and HBGB-6 were incubated for 24 hours in 5 ml of plasma, 10 ml of saline, or 10 ml of Ringer's lactate. After incubation, 1 ml was obtained from each solution and assayed for heparin. Segments of each graft that leached off an equivalent of 1 U of heparin/ml (i.e., 1 mm2 of HBGA, 5 mm2 of HBGB-8, and 20 mm2 of HBGB-6) were incubated with 0.15 ml of plasma with HAAbs (six samples per graft) for 30 minutes at 25 degrees C. The grafts were removed, and 0.1 ml of normal-donor, platelet-rich plasma was added. The samples were placed in an aggregometer and allowed to react until positive aggregation occurred or 27 minutes had elapsed. Segments of non-heparin-bonded polyester grafts served as controls.
  
  
  RESULTS
  Heparin leached off all grafts in plasma (mean values: HBGA, 83.4 U of heparin/ml; HBGB-8, 4 U of heparin/ml; HBGB-6, 6.2 U of heparin/ml). In normal saline, the mean heparin concentrations were lower (HBGA, 10.8 U of heparin/ml; HBGB-8, 0 U of heparin/ml; HBGB-6, 0.01 U of heparin/ml. The mean heparin concentration after incubation in Ringer's lactate were 10 U of heparin/ml for HBGA, 0 U of heparin/ml HBGB-8, and 0.22 U of heparin/ml HBGB-6. All of the HBGs induced platelet aggregation inHAAb-positive plasma. None of the control grafts induced platelet aggregation in HAAb-positive plasma.
  
  
  CONCLUSIONS
  All HBGs leached heparin into plasma, and all induced platelet aggregation in the presence of HAAbs. The possibility of sensitizing patients to heparin leeching from a HBG with the activation of platelets and secondary thrombosis strongly suggests that HBG be used with great caution. Other methods for inducing graft thromboresistance should be developed.
authors.affiliation: Department of Surgery, University of Missouri-Columbia, 65212, USA.
authors.forename: J I
authors.initials: JI
authors.lastname: Almeida
authors.forename: T K
authors.initials: TK
authors.lastname: Liem
authors.forename: D
authors.initials: D
authors.lastname: Silver
mesh_terms: D000906:Antibodies / Q000276:immunology*; D000925:Anticoagulants / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001157:Arterial Occlusive Diseases / Q000601:surgery; D001769:Blood; D001792:Blood Platelets / Q000276:immunology*; D001807:Blood Vessel Prosthesis; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006493:Heparin / Q000032:analysis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007552:Isotonic Solutions; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects* / Q000276:immunology; D011091:Polyesters / Q000737:chemistry; D011093:Polyethylene Terephthalates / Q000737:chemistry; D011474:Prosthesis Design; D000077325:Ringer's Lactate; D012965:Sodium Chloride; D013927:Thrombosis / Q000276:immunology / Q000517:prevention & control
chemical_list: D000906:Antibodies; D000925:Anticoagulants; D007552:Isotonic Solutions; D011091:Polyesters; D011093:Polyethylene Terephthalates; D000077325:Ringer's Lactate; D012965:Sodium Chloride; D006493:Heparin