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.

source: © 2015 European Heart Journal

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 mm2 vs. late: 2485 ± 1778 per mm2; P = 0.44); neutrophils represented the most prominent subset (early: 1364 ± 923 per mm2 vs. late: 1428 ± 1023 per mm2; 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.[Read more….]

eukocyte accumulation in stent thrombus specimens.

Fig. Leukocyte accumulation in stent thrombus specimens. (A) Leukocyte accumulation in human stent thrombus specimens. Left images: Haematoxylin–eosin staining (n = 253). Arrows indicate granulocytes, arrowheads indicate mononuclear cells. Right images: immunofluorescence staining of neutrophil elastase to identify neutrophils (n = 229). Nuclei are counterstained with Hoechst. Bars, 200 ”m (upper row) and 50 ”m (bottom row); (B) Quantification of leukocytes and neutrophils in early (n = 67) vs. late (n = 162) stent thrombosis (leukocytes: P = 0.44; neutrophils: P = 0.81); (C) Leukocytes and neutrophils in stent thrombosis from drug-eluting stents (n = 149) and bare metal stents (n = 73) and in thrombi aspirated from patients with spontaneous myocardial infarction (spont. myocardial infarction; n = 104) (P < 0.05 for drug-eluting stents vs. spont. myocardial infarction and bare metal stents vs. spont. myocardial infarction). Shown are mean + SD, each symbol in (B) and (C) represents one individual patient.

++These authors contributed equally to this work.
Julia Riegger, Robert A. Byrne, Michael Joner, Sue Chandraratne, Anthony H. Gershlick, Jurrien M. ten Berg, Tom Adriaenssens, Giulio Guagliumi, Thea C. Godschalk, Franz-Josef Neumann, Dietmar Trenk, Laurent J. Feldman, Philippe Gabriel, Steg Walter Desmet, Fernando Alfonso, Alison H. Goodall, Roman Wojdyla, Dariusz Dudek, Vanessa Philippi, Sheryl Opinaldo, Anna Titova, Nikesh Malik, James Cotton, Darshni A. Jhagroe, Antonius A.C.M. Heestermans, Peter Sinnaeve, Paul Vermeersch, Christian Valina, Christian Schulz, Adnan Kastrati, Steffen Massberg the Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort (PRESTIGE) Investigators On Behalf of the Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort (PRESTIGE) Investigators,Tom Adriaenssens, Ian Buysschaert, Mickaël Chausson, Dries De Cock, Jo Dens, Emanuele Barbato, Walter Desmet, Sandrine Gautier, Paul Vermeersch, Peter Sinnaeve, Helene Abergel, Laurent Feldman, Martine Jandrot-Perrus, Didier Letourneur, Pierre Mangin, Véronique Olivier, Caroline Roques, Robert A. Byrne, Sue Chandraratne, Matthias Gratz, Michael Joner, Adnan Kastrati, Elisabeth Kennerknecht, Ildiko Konrad, Tobias Koppara, Steffen Massberg, Franz-Josef Neumann, Vasilis Ntziachristos, Sheryl Opinaldo, Vanessa Philippi, Julia Riegger, Amir Rosenthal, Alexander Rzany, Christian Schulz, Kristin Steigerwald, Tomohiso Tada, Anna Titova, Dietmar Trenk, Christian Valina, Andreas Vogelsang, Erion Xhepa, Chiara Bernelli, Micol Coccato, Giulio Guagliumi, Kenichi Komukai, Vasile Sirbu, Garry Kerch, Giovanni Amoroso, Jurriën ten Berg, Willem J.M. Dewilde, Thea C. Godschalk, Antonius A.C.M. Heestermans, Darshni A. Jhagroe, Joanne J. Wykrzykowska, Mark H.M. Winkens, Dariusz Dudek, Ɓukasz Rzeszutko, Roman Wojdyla, Wojciech Zasada, Fernando Alfonso, Javier Cuesta, Miguel Medina, Colin Berry, James Cotton, Nick Curzen, Margaret McEntegart, Robert Gerber, Anthony Gershlick, Alison H. Goodall, Simon Hetherington, Jonathan Hill, Damian Kelly, Nikesh Malik, Keith Oldroyd, Helen Routledge, Joanne Shannon, Venkatesan Suresh, Azfar Zahman.

European Heart Journal, Volume 37, Issue 19, 14 May 2016, Pages 1538–1549, https://doi.org/10.1093/eurheartj/ehv419