Recruitment of leukocytes is a hallmark of stent thrombosis

August 30, 2015

London, UK - 30 Aug 2015: Recruitment of leukocytes is a hallmark of stent thrombosis, according to results from the PRESTIGE study presented today 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."
-end-


European Society of Cardiology

Related Neutrophils Articles from Brightsurf:

The unexpected repair function of neutrophils
Scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) have discovered that neutrophils, the most abundant cells of the innate immune system, have many more functions in the body than previously thought.

Cells sacrifice themselves to boost immune response to viruses
Whether flu or coronavirus, it can take several days for the body to ramp up an effective response to a viral infection.

LJI team gets first-ever look at a rare but vital stem cell in humans
Scientists at La Jolla Institute for Immunology (LJI) have tracked down the rare stem cells that generate neutrophils in human bone marrow.

COVID-19 - The virus and the vasculature
In severe cases of COVID-19, the infection can lead to obstruction of the blood vessels in the lung, heart and kidneys.

How rod-shaped particles might distract an out-of-control COVID immune response
A long-ignored white blood cell may be central to the immune system overreaction that is the most common cause of death for COVID-19 patients--and University of Michigan researchers found that rod-shaped particles can take them out of circulation.

A better model for neutrophil-related diseases
Neutrophils are critical immune cells for antimicrobial defense, but they can exacerbate a number of diseases, perhaps including COVID-19.

Tumor secreted ANGPTL2 facilitates recruitment of neutrophils to the lung to promote lung pre-metastatic niche formation and targeting ANGPTL2 signaling affects metastatic disease
The authors determined that tumor-derived ANGPTL2 stimulates lung epithelial cells, which is essential for primary tumor-induced neutrophil recruitment in lung and subsequent pre-metastatic niche formation.

Neutrophils are equipped with a 'disarmament' program that prevents the immune system going 'out of control'
The new finding, published in Nature Immunology, could have major implications for the understanding and treatment of disorders such as myocardial infarction, stroke, and acute inflammatory processes.

Scientists link common immune cell to failure of checkpoint inhibitors in lung cancer
For many lung cancer patients, the best treatment options involve checkpoint inhibitors, but the drugs only help a small subset of patients.

New technology promises improved treatment of inflammatory diseases
A study led by researchers at Washington State University has uncovered a potential new treatment approach for diseases associated with inflammation, including sepsis and stroke.

Read More: Neutrophils News and Neutrophils Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.