title: Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours.
abstract: Increased thrombogenicity of drug-eluting stents (DESs) has recently been reported. The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating. Circulating pre- and post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs. Stent implantations were performed after pretreatment with aspirin and clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups AST-DES, n = 12; and AST-Bare, n = 7) died mean 6.3 +/- 2.9 h after stent implantation from AST. The remaining 122 control (C) pigs (groups C-DES, n = 76, and C-Bare, n = 46) survived the 1-month follow-up. Non-significantly elevated levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV was increased significantly in the groups ASTDES and AST-Bare as compared with the groups C-DES and C-Bare (11.73 +/- 1.12 and 11.6 +/- 0.68 vs. 8.85 +/- 0.78 and 9.04 +/- 0.81 fL; p < 0.001), similarly to TF-ag (189.1 +/- 87.5 and 127 +/- 34.9 vs. 42.5 +/- 24.6 and 35.3 +/- 37.6 pg/ml; p < 0.001, respectively), Tfact (3.23 +/- 0.95 and 2.73 +/- 1.68 vs. 1.43 +/- 1.12 and 1.61 +/- 1.31 pM; p < 0.01, respectively) and PAI-1 (99.1 +/- 15.8 and 99 +/- 14.7 vs.53.4 +/- 40.2 and 46.9 +/- 42.4 ng/ml;p < 0.01, respectively). Multivariate analysis revealed elevated post-stenting plasma levels of TF-ag (p = 0.016) and MPV (p = 0.001) as independent risk factors for developing AST within the first 24 h in a porcine coronary stent model.
authors.affiliation: Department of Cardiology, Medical University of Vienna, Vienna, Austria. mariann.gyongyosi@meduniwien.ac.at
authors.forename: Mariann
authors.initials: M
authors.lastname: Gyöngyösi
authors.forename: Christoph
authors.initials: C
authors.lastname: Strehblow
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperker
authors.forename: Akos
authors.initials: A
authors.lastname: Hevesi
authors.forename: Rita
authors.initials: R
authors.lastname: Garamvölgyi
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Petrási
authors.forename: Noemi
authors.initials: N
authors.lastname: Pavo
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.forename: Csaba
authors.initials: C
authors.lastname: Csonka
authors.forename: Tamås
authors.initials: T
authors.lastname: Csont
authors.forename: Christer
authors.initials: C
authors.lastname: Sylvèn
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Declerck
authors.forename: Imre
authors.initials: I
authors.lastname: Pavo
authors.forename: Johann
authors.initials: J
authors.lastname: Wojta
authors.forename: Dietmar
authors.initials: D
authors.lastname: Glogar
authors.forename: Kurt
authors.initials: K
authors.lastname: Huber
mesh_terms: D000792:Angiography; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D023903:Coronary Restenosis; D003331:Coronary Vessels / Q000473:pathology* / Q000648:ultrastructure; D005342:Fibrinolysis; D008855:Microscopy, Electron, Scanning; D015539:Platelet Activation; D015607:Stents; D013552:Swine; D013917:Thrombin / Q000378:metabolism; D013925:Thromboplastin / Q000378:metabolism*; D013927:Thrombosis / Q000097:blood*; D013997:Time Factors
chemical_list: D013925:Thromboplastin; D013917:Thrombin