heparitin-sulfate and Graft-Occlusion--Vascular

Thrombogenicity and neointimal hyperplasia are major causes for synthetic vascular graft failure. Bioactive coatings like heparin have improved patency by reducing thrombogenicity, but neointimal hyperplasia still remains an unsolved problem. Surface coatings with heparan sulfate (HS), the major component of the glycocalyx of endothelial cells, have shown reduced platelet and cell adhesion in vitro. The aim of the study was to evaluate the in vivo surface properties of expanded ePTFE vascular grafts with a semisynthetic HS-like coating (SSHS).. ePTFE vascular grafts (n = 16, diameter 3.5 mm) covalently coated with SSHS were compared with uncoated grafts (n = 16) of the same diameter in a carotid interposition model in 16 sheep. The grafts were harvested at 20 wk for histological and morphometric analysis.. SSHS-coated grafts showed less neointima formation than uncoated grafts (P < 0.001). There was no evidence for cell or protein adhesion to SSHS-coated grafts, whereas the surface of uncoated ePTFE grafts was covered with a confluent circular layer of neointima. No difference was found concerning reactions at the anastomotic site of the genuine carotid vessel, both groups displayed neointimal hyperplasia.. ePTFE grafts covalently coated with a semisynthetic SSHS-glycosaminoglycan successfully mimicked the endothelial glycocalyx. They displayed excellent antiadhesive properties preventing neointimal formation on the graft surface. The results indicate that a biomimetic SSHS coating may be a useful component of bioengineered grafts and an alternative to synthetic surfaces and endothelial seeding.

Topics: Animals; Biomimetic Materials; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Carotid Arteries; Cell Adhesion; Cell Proliferation; Coated Materials, Biocompatible; Endothelial Cells; Female; Graft Occlusion, Vascular; Heparitin Sulfate; Hyperplasia; Materials Testing; Models, Animal; Neointima; Polytetrafluoroethylene; Prosthesis Design; Sheep, Domestic; Time Factors

Acute graft thrombosis is a severe complication in vascular surgery that may require limb amputation or even cause death. Because nearly all patients undergoing vascular surgery have had previous exposure to heparin, the presence of heparin-related anti-platelet antibodies typical for heparin-associated thrombocytopenia (HAT) is one underlying possible mechanism of acute graft thrombosis. Although thrombocytopenia is a typical finding of HAT, it is not clear whether the occurrence of clinically important HAT is necessarily associated with thrombocytopenia.. Ten out of 246 patients undergoing vascular surgery were diagnosed with HAT because of otherwise unexplained acute graft thrombosis that required recurrent surgical interventions.. In all of the 10 patients, heparin-related anti-platelet antibodies were detected although the platelet counts were within the normal range. When HAT was diagnosed, heparin administration was stopped and, after autoantibody cross-reactivity with the heparinoid Danaparoid had been excluded, anticoagulation was continued using this anticoagulant. After heparin therapy was discontinued none of the 10 patients developed further thrombotic complications.. The data presented demonstrate clearly that a normal platelet count does not exclude the possibility of HAT. As a consequence of this, HAT should be suspected in patients who develop thrombotic complications during heparin treatment, regardless of the actual platelet counts.

Topics: Adult; Aged; Anastomosis, Surgical; Arterial Occlusive Diseases; Autoantibodies; Blood Platelets; Blood Vessel Prosthesis; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Female; Graft Occlusion, Vascular; Heparin; Heparinoids; Heparitin Sulfate; Humans; Intraoperative Complications; Male; Middle Aged; Platelet Count; Reoperation; Thrombosis; Vascular Patency