Heparin has now been incorporated into multiple prosthetic vascular grafts, including Dacron (polyethylene terephthalate) grafts and the GORE® PROPATEN® Vascular Graft (Gore & Associates). A key aspect of heparinbonding technology is the chemical means by which the heparin is bonded to the device lumen. The functionality of the bonded surface depends not just on the amount of heparin that is bound to the graft, but also the activity of the bonded heparin itself and whether it is able to interact freely with the blood. These three factors—the presence, availability, and activity of heparin dictate the efficacy of the bonded surface as a thromboresistant coating and differ based on which heparin-bonding method is employed.
One way of demonstrating the difference in the functionality of heparin applied to a surface using alternative bonding methods is an in vitro recirculating human blood model. In this model, flexible medical tubing is coated with heparin and exposed to freshly collected, nonanticoagulated whole blood. After 1 hour of blood contact, adsorbed plasma proteins are eluted from the tubing surface and separated by gel electrophoresis. The identities of the proteins are then determined by a Western blot. A tube that is coated with functional, available heparin should have more elutable antithrombin than a tube coated with heparin that is either nonfunctional (having had its active site removed) or not available. The Western blot technique revealed a great deal of antithrombin bound to a tubing surface that was coated using the CBAS Heparin Surface technique, suggesting that the heparin on the surface is active and available (Figure 1).
The presence of active available heparin should result in very little platelet activation. Indeed, the Western blot revealed minimal platelet activation, as demonstrated by very little platelet factor 4 eluted from the surface. Thus, in an in vitro assay, heparin bonding (using the CBAS® Heparin Surface technique) resulted in a great deal of bound antithrombin and minimal platelet activation. In contrast, under the same assay conditions, a randomly bonded heparin surface activated platelets as much as a nonfunctional heparin surface and did not bind as much antithrombin as the CBAS® Heparin Surface. These results would suggest that the randomly bonded heparin technique does not perform as well as CBAS® Heparin Surface technology in vitro.
While both in vitro and in vivo studies have demonstrated that heparin bonding is effective in the short term, researchers are beginning to investigate whether heparin bonding works in the long term.1-2 An evaluation of an 8-year-old GORE® PROPATEN® Vascular Graft explant suggested that the heparin technology continued to be effective as measured by an assay for heparin activity (antithrombin binding). Results from one nonrandomized study comparing 3-year experience with standard expanded polytetrafluoroethylene (ePTFE) to the CBAS® Heparin Surface on the GORE® PROPATEN® Vascular Graft suggest that the latter technology affords better long-term outcomes for femoropopliteal grafts.
Currently, there are no long-term data on alternative heparin-bonded grafts. In the absence of such data, surgeons cannot assume that all heparin-bonding technologies will be equally effective.
CBAS® Heparin Surface bonding is likely providing long-term antithrombotic protection to the ePTFE surface. It is possible, however, that other methods of “attaching” heparin to ePTFE may not have such longterm protective effects. Vascular surgeons need to be aware of the construct of newer grafts in order to make valid determinations regarding the potential benefits of trying new, non-autogenous materials.
Russell H. Samson, MD, FACS, RVT, is Clinical Professor of Surgery at Florida State University Medical School and is an attending surgeon with Sarasota Vascular Specialists in Sarasota, Florida. He has disclosed that he has received compensation from Gore for participating in the Summit and has received honoraria from Gore for writing this article. Dr. Samson may be reached at [email protected]
- Lösel-Sadée H, Alefelder C. Heparin-bonded expanded polytetrafluoroethylene graft for infragenicular bypass: five-year results. J Cardiovasc Surg. 2009;50:339-343.
- Pulli R, Dorigo W, Piffaretti G, et al. A decade of arterial bypass results with the Gore Propaten Vascular Graft: long term clinical results from more than 1,000 cases in the multicenter Italian Registry. Ital J Vasc Endovasc Surg. 2014;21:101-107.