Heparin-bonded grafts induce platelet aggregation in the presence of heparin-associated antiplatelet antibodies

Purpose: 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 nun HBG from company A (HBGA) and 8 nun 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°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 leeched 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.