Heparin-resistant thrombus formation by endovascular stents in baboons. Interruption by a synthetic antithrombin

W. C. Krupski, A. Bass, A. B. Kelly, U. M. Marzec, S. R. Hanson, L. A. Harker

Research output: Contribution to journalArticlepeer-review

Abstract

Intravascular mechanical support has been proposed as a solution to the frequent occurrence of vascular narrowing and occlusion after transluminal balloon angioplasty or surgical endarterectomy. Although several endovascular stents are currently in clinical use for angioplasty of larger vessels, acute thrombosis is a troublesome complication of their use with coronary angioplasty. To study thrombus formation associated with metallic mesh endoprostheses, we have evaluated stents placed inside 3-mm expanded polytetrafluoroethylene (ePTFE) grafts incorporated into chronic exteriorized arteriovenous silicone rubber shunts in babboons. We have also compared the antithrombotic capacities of heparin and the synthetic antithrombin D-phenylalanyl-L-prolyl-L-arginyl-chloromethylketone (D-FPRCH2Cl) to interrupt this platelet-dependent process for two different endovascular stents. Acute platelet deposition was continuously measured during 1 hour using gamma camera imaging of platelets labeled with indium-111 oxine. On untreated control ePTFE grafts (n = 11), 0.87 ± 0.15 x 109 platelets/cm were deposited during 60 minutes. In contrast, balloon-expandable endovascular stents within ePTFE (n = 6) accumulated 4.37 ± 0.68 x 109 platelets/cm (p = 0.003 compared with controls), and self-expandable stents (n = 6) accumulated 3.91 ± 0.42 x 109 platelets/cm (p = 0.006 compared with controls); no difference between stents was detected in this test system (p > 0.5). Systemic heparin treatment did not reduce platelet deposition (4.20 ± 0.41 x 109 platelets/cm at 60 minutes; p > 0.5). Continuous infusion of D-FPRCH2Cl (100 nmol/kg · min) begun immediately before placing stented grafts in the shunts maintained plasma levels of D-FPRCH2Cl at 4.30 ± 0.50 μg/ml and significantly reduced platelet deposition (0.45 ± 0.41 x 109 platelets/cm for balloon-expandable stents; p = 0.0008 compared with untreated stents, and 0.01 ± 0.01 x 109 platelets/cm for self-expandable stents; p = 0.01 compared with untreated stents). The accumulation of abundant thrombotic material, as demonstrated by electron microscopy in stented grafts, was interrupted by D-FPRCH2Cl treatment. We conclude that stainless-steel endovascular stents within ePTFE grafts induce platelet-dependent, heparin-resistant thrombosis under high-flow conditions and that systemic infusion of D-FPRCH2Cl abolishes thrombus formation.

Original languageEnglish
Pages (from-to)570-577
Number of pages8
JournalCirculation
Volume82
Issue number2
DOIs
StatePublished - 1990
Externally publishedYes

Keywords

  • D-phenylalanyl-L-prolyl-L- arginyl-chloromethylketone, D-FPRCHCl
  • endoprostheses
  • restenosis
  • stents
  • thrombosis

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