DIFFERENTIAL STIMULATION OF MACROPHAGE PROCOAGULANT ACTIVITY BY VASCULAR GRAFTS

Purpose: The mechanism by which some graft materials are more thrombogenic than others is poorly understood. We hypothesized that differential induction of macrophage procoagulant activity (PCA) by various materials may contribute to variable thrombogenicity. Methods: Thioglycollate-elicited murine peritoneal macrophages were added to disks of Dacron and expanded polytetrafluoroethylene (ePTFE). After adherence, macrophages were incubated with and without endotoxin (lipopolysaccharide) and then recovered by sonication for determination of PCA with a one-step clotting bioassay. Results: PCA was significantly higher in cells after incubation on Dacron compared with ePTFE both in the absence of lipopolysaccharide (243 +/- 76 vs 68 +/- 39 mU, n = 4) and after stimulation with lipopolysaccharide (491 +/- 137 vs 139 +/- 41 mU, n = 4) (p < 0.01, analysis of variance). Using factor-deficient plasmas, we found that this PCA was consistent with tissue factor. This differential induction of PCA was related to increased macrophage adherence to Dacron compared to that to ePTFE (9374 +/- 1158 vs 2111 +/- 330 cells/mm2; n = 4; p < 0.01, analysis of variance). Conclusions: The thrombogenic nature of Dacron correlates with its ability to adhere macrophages and induce PCA. Strategies aimed at modulating these effects may reduce the thrombogenicity of vascular grafts and therefore potentially the incidence of graft thrombosis.