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.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSION
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.
['Riegger|Julia|J|', 'Byrne|Robert A|RA|', 'Joner|Michael|M|', 'Chandraratne|Sue|S|', 'Gershlick|Anthony H|AH|', 'Ten Berg|Jurrien M|JM|', 'Adriaenssens|Tom|T|', 'Guagliumi|Giulio|G|', 'Godschalk|Thea C|TC|', 'Neumann|Franz-Josef|FJ|', 'Trenk|Dietmar|D|', 'Feldman|Laurent J|LJ|', 'Steg|Philippe Gabriel|PG|', 'Desmet|Walter|W|', 'Alfonso|Fernando|F|', 'Goodall|Alison H|AH|', 'Wojdyla|Roman|R|', 'Dudek|Dariusz|D|', 'Philippi|Vanessa|V|', 'Opinaldo|Sheryl|S|', 'Titova|Anna|A|', 'Malik|Nikesh|N|', 'Cotton|James|J|', 'Jhagroe|Darshni A|DA|', 'Heestermans|Antonius A C M|AA|', 'Sinnaeve|Peter|P|', 'Vermeersch|Paul|P|', 'Valina|Christian|C|', 'Schulz|Christian|C|', 'Kastrati|Adnan|A|', 'Massberg|Steffen|S|', '|||']
D000368:Aged D001792:Blood Platelets D003328:Coronary Thrombosis D054855:Drug-Eluting Stents D004804:Eosinophils D005260:Female D005340:Fibrinogen D006083:Graft Occlusion, Vascular D006801:Humans D007958:Leukocyte Count D016131:Lymphocyte Subsets D008297:Male D009504:Neutrophils D062645:Percutaneous Coronary Intervention D011446:Prospective Studies D011475:Prosthesis Failure D015607:Stents D017131:Thrombectomy
Histopathology Stent thrombosis Thrombus aspiration Neutrophil extracellular traps Neutrophils Platelets Eosinophils