title: Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium.
abstract: Stent thrombosis (ST) is a rare but serious complication following percutaneous coronary intervention. Analysis of thrombus composition from patients undergoing catheter thrombectomy may provide important insights into the pathological processes leading to thrombus formation. We performed a large-scale multicentre study to evaluate thrombus specimens in patients with ST across Europe.
  
  
  
  Patients presenting with ST and undergoing thrombus aspiration were eligible for inclusion. Thrombus collection was performed according to a standardized protocol and specimens were analysed histologically at a core laboratory. Serial tissue cross sections were stained with haematoxylin-eosin (H&E), Carstairs and Luna. Immunohistochemistry was performed to identify leukocyte subsets, prothrombotic neutrophil extracellular traps (NETs), erythrocytes, platelets, and fibrinogen.
  
  
  
  Overall 253 thrombus specimens were analysed; 79 (31.2%) from patients presenting with early ST, 174 (68.8%) from late ST; 79 (31.2%) were from bare metal stents, 166 (65.6%) from drug-eluting stents, 8 (3.2%) were from stents of unknown type. Thrombus specimens displayed heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments most abundant; mean platelet coverage was 57% of thrombus area. Leukocyte infiltrations were hallmarks of both early and late ST (early: 2260 ± 1550 per mm(2) vs. late: 2485 ± 1778 per mm(2); P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm(2) vs. late: 1428 ± 1023 per mm(2); P = 0.81). Leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction. Neutrophil extracellular traps were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-and everolimus-eluting stents.
  
  
  
  In a large-scale study of histological thrombus analysis from patients presenting with ST, thrombus specimens displayed heterogeneous morphology. Recruitment of leukocytes, particularly neutrophils, appears to be a hallmark of ST. The presence of NETs supports their pathophysiological relevance. Eosinophil recruitment suggests an allergic component to the process of ST.
authors.affiliation: Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich 81377, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Riegger
authors.affiliation: DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany Deutsches Herzzentrum München, Klinik an der Technische, Universität München, Lazarettstrasse 36, Munich 80636, Germany.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Byrne
authors.affiliation: Deutsches Herzzentrum München, Klinik an der Technische, Universität München, Lazarettstrasse 36, Munich 80636, Germany CVPath Institute, Gaithersburg, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Joner
authors.affiliation: Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich 81377, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Sue
authors.initials: S
authors.lastname: Chandraratne
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and Leicester NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
authors.forename: Anthony H
authors.initials: AH
authors.lastname: Gershlick
authors.affiliation: Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Jurrien M
authors.initials: JM
authors.lastname: Ten Berg
authors.affiliation: Department of Cardiology, University Hospitals Leuven, Leuven, Belgium Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Adriaenssens
authors.affiliation: Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Guagliumi
authors.affiliation: Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Thea C
authors.initials: TC
authors.lastname: Godschalk
authors.affiliation: Universitäts-Herzzentrum Freiburg Bad Krozingen, Germany.
authors.forename: Franz-Josef
authors.initials: FJ
authors.lastname: Neumann
authors.affiliation: Universitäts-Herzzentrum Freiburg Bad Krozingen, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Trenk
authors.affiliation: INSERM, U-1148, Paris, France DHU FIRE, Hôpital Bichat, AP-HP, Paris, France Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France.
authors.forename: Laurent J
authors.initials: LJ
authors.lastname: Feldman
authors.affiliation: INSERM, U-1148, Paris, France DHU FIRE, Hôpital Bichat, AP-HP, Paris, France Université Paris-Diderot, Sorbonne Paris-Cité, Paris, France NHLI, Royal Brompton Hospital, Imperial College, London, UK.
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.affiliation: Department of Cardiology, University Hospitals Leuven, Leuven, Belgium Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Walter
authors.initials: W
authors.lastname: Desmet
authors.affiliation: Hospital Universitario de La Princesa, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Alfonso
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and Leicester NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
authors.forename: Alison H
authors.initials: AH
authors.lastname: Goodall
authors.affiliation: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie, Krakow, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Wojdyla
authors.affiliation: Samodzielny Publiczny Zaklad Opieki Zdrowotnej Szpital Uniwersytecki w Krakowie, Krakow, Poland.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Dudek
authors.affiliation: Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich 81377, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Philippi
authors.affiliation: Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich 81377, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Sheryl
authors.initials: S
authors.lastname: Opinaldo
authors.affiliation: Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich 81377, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Titova
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester and Leicester NIHR Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK.
authors.forename: Nikesh
authors.initials: N
authors.lastname: Malik
authors.affiliation: The Royal Wolverhampton Hospitals NHS Trust, Heart and Lung Centre, New Cross Hospital, Wolverhampton WV10 0QP, UK.
authors.forename: James
authors.initials: J
authors.lastname: Cotton
authors.affiliation: Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Darshni A
authors.initials: DA
authors.lastname: Jhagroe
authors.affiliation: Department of Cardiology, Medical Center Alkmaar, Alkmaar, The Netherlands.
authors.forename: Antonius A C M
authors.initials: AA
authors.lastname: Heestermans
authors.affiliation: Department of Cardiology, University Hospitals Leuven, Leuven, Belgium Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Sinnaeve
authors.affiliation: Antwerp Cardiovascular Institute, ZNA Middelheim, Lindendreef 1, Antwerpen B-2020, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Vermeersch
authors.affiliation: Universitäts-Herzzentrum Freiburg Bad Krozingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Valina
authors.affiliation: Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich 81377, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schulz
authors.affiliation: DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany Deutsches Herzzentrum München, Klinik an der Technische, Universität München, Lazarettstrasse 36, Munich 80636, Germany steffen.massberg@med.uni-muenchen.de kastrati@dhm.mhn.de.
authors.forename: Adnan
authors.initials: A
authors.lastname: Kastrati
authors.affiliation: Medizinische Klinik und Poliklinik I, Ludwig-Maximilians-Universität, Marchioninistrasse 15, Munich 81377, Germany DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany steffen.massberg@med.uni-muenchen.de kastrati@dhm.mhn.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Massberg
mesh_terms: D000368:Aged; D001792:Blood Platelets; D003328:Coronary Thrombosis / Q000378:metabolism / Q000517:prevention & control*; D054855:Drug-Eluting Stents; D004804:Eosinophils; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006801:Humans; D007958:Leukocyte Count; D016131:Lymphocyte Subsets; D008297:Male; D009504:Neutrophils; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D011446:Prospective Studies; D011475:Prosthesis Failure; D015607:Stents; D017131:Thrombectomy / Q000379:methods
chemical_list: D005340:Fibrinogen
keywords: Eosinophils; Histopathology; Neutrophil extracellular traps; Neutrophils; Platelets; Stent thrombosis; Thrombus aspiration