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Recruitment of leukocytes is a hallmark of stent thrombosis

Recruitment of leukocytes is a hallmark of stent thrombosis, according to results from the PRESTIGE study presented at ESC Congress1 and published in European Heart Journal.2 The findings suggest that immune cell mediated thrombotic processes may be a realistic target for novel therapies to prevent stent thrombosis.

“Stent thrombosis (ST) is a life-threatening complication of percutaneous coronary intervention and recent large scale clinical registries reported an incidence of up to 0.4-0.6% per year,” said principal investigator Professor Steffen Massberg, director of the Department of Cardiology at the Ludwig-Maximilians University (LMU) Munich, Germany. “The majority of ST patients present with acute myocardial infarction and rates of mortality following presentation are as high as 20-40%.”

He continued: “The incidence of ST is highest within the first 30 days after stenting, however, patients treated with drug-eluting stents (DES) – the dominant devices used in contemporary practice – have been shown to be at higher risk of late ST. Clinical practice guidelines therefore recommend a more prolonged duration of dual antiplatelet therapy after stenting with DES as compared to after bare metal stents.”

The PREvention of late Stent Thrombosis by an Interdisciplinary Global European effort (PRESTIGE) consortium was established to investigate the mechanisms triggering stent thrombosis across Europe. As part of this study, thrombus specimens retrieved from catheter thrombectomy were systematically collected and analysed in a central core laboratory at the German Heart Centre in Munich, Germany. The main findings from the histopathological evaluation of thrombus specimens from these patients are presented today by Dr Julia Riegger, a cardiologist at the Department of Cardiology at the LMU in Munich.

Dr Riegger said: “Although some pathological processes associated with ST have been identified, the triggering mechanisms remain incompletely understood, and the influence of factors such as timing of ST after the procedure, stent type or polymer coating is poorly characterised. In particular, the potential role of immune cells and related extracellular components has not been elucidated in detail.”

The PRESTIGE substudy presented during ESC Congress included patients with ST and undergoing thrombus aspiration at nine centres in Europe between 2010 and 2014. Thrombus specimens were analysed histologically at a core laboratory. Overall 253 thrombus specimens were analysed. Of these, 79 (31.2%) were from patients presenting with early ST and 174 (68.8%) from late ST, while 79 (31.2%) were from bare metal stents, 166 (65.6%) from DES and 8 (3.2%) from stents of unknown type.

The investigators found that the thrombus specimens had heterogeneous morphology with platelet-rich thrombus and fibrin/fibrinogen fragments being most abundant. Leukocyte infiltrations were hallmarks of both early and late ST with neutrophils representing the most prominent subset. Neutrophils were found in similar amounts in early and late ST. “It is important to note that leukocyte counts were significantly higher compared with a control group of patients with thrombus aspiration in spontaneous myocardial infarction,” said Professor Massberg.

Neutrophil extracellular traps (NETs), which are prothrombotic extracellular DNA released by neutrophils, were observed in 23% of samples. Eosinophils were present in all stent types, with higher numbers in patients with late ST in sirolimus-eluting and everolimus-eluting stents. “The presence of NETs supports their pathophysiological relevance in ST, while eosinophil recruitment suggests an allergic component to the process of ST,” said Professor Massberg.

He concluded: “Our results suggest that immune cell mediated thrombotic processes may be a realistic target for novel therapies to prevent ST. Inhibition of triggers, such as extracellular nucleic acids activating the contact phase, may not only result in efficient anticoagulation in the setting of ST but might also yield less therapy-associated bleeding. Future studies should evaluate whether inhibition of immune cell-driven thrombotic pathways are effective and safe in clinical practice.”