Propagation of thrombosis by neutrophils and extracellular nucleosome networks

Pfeiler, Susanne; Stark, Konstantin; Maßberg, Steffen; Engelmann, Bernd

doi:10.3324/haematol.2016.142471

Cited by 108 publications

(110 citation statements)

References 78 publications

(94 reference statements)

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“…Another potential mechanism could be the NET-induced activation of both the extrinsic and contact pathway of blood coagulation. 35,36 In our cohort, the higher NLR group showed a trend for higher fibrinogen accumulation in peripheral. A recent study found that patients with elevated neutrophil counts had a lower risk of hematoma expansion following acute ICH, 37 may also be explained by the increased coagulation by neutrophils.…”

Section: P-valuementioning

confidence: 51%

“…Neutrophils originated from the blood circulating could be found within the brain as early as 4 hours in mice ICH models . And the results from the literature suggest that neutrophils could externalize decondensed nucleosomes and granule proteins to form neutrophil extracelluar traps (NETs) in some cases . In this context, with the pre‐existing cerebral microangiopathy in ICH, elevated NLR was prone to have NET increasing and thus led to microvascular thrombosis.…”

Section: Discussionmentioning

confidence: 76%

“…In this context, with the pre‐existing cerebral microangiopathy in ICH, elevated NLR was prone to have NET increasing and thus led to microvascular thrombosis. Another potential mechanism could be the NET‐induced activation of both the extrinsic and contact pathway of blood coagulation . In our cohort, the higher NLR group showed a trend for higher fibrinogen accumulation in peripheral.…”

Section: Discussionmentioning

confidence: 76%

“…34 And the results from the literature suggest that neutrophils could externalize decondensed nucleosomes and granule proteins to form neutrophil extracelluar traps (NETs) in some cases. 35 In this context, with the pre-existing cerebral microangiopathy in ICH, elevated NLR was prone to have NET increasing and thus led to microvascular thrombosis. Another potential mechanism could be the NET-induced activation of both the extrinsic and contact pathway of blood coagulation.…”

Section: P-valuementioning

confidence: 99%

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Early elevated neutrophil‐to‐lymphocyte ratio associated with remote diffusion‐weighted imaging lesions in acute intracerebral hemorrhage

Chen

et al. 2019

CNS Neurosci Ther

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Aims To explore the relationship between the circulating neutrophil‐to‐lymphocyte ratio (NLR) and the remote diffusion‐weighted imaging lesions (R‐DWILs) after spontaneous intracerebral hemorrhage (ICH). Methods Consecutive patients with spontaneous ICH were prospectively collected from November 2016 to May 2018 and retrospectively analyzed. We included subjects who presented within 24 hours after symptom onset and were free of detectable infections on admission or in hospital. Blood samples were obtained at 24‐48 hours after ICH ictus, while all complete MRI scans were performed at 5‐8 days. R‐DWILs were defined as focal hyperintensities remote from the site of the ICH or the peri‐hematoma regions. NLR was calculated by dividing the absolute neutrophil counts by the absolute lymphocyte counts. Multivariate binary logistic regression models were generated to evaluate the relationship between NLR and R‐DWILs. Results One hundred sixty‐three subjects met eligibility criteria (age 62.3 ± 13.6 years, 60.7% males), of whom 31(19.0%) experienced R‐DWILs. Higher circulating NLR was documented in patients with R‐DWILs. With the best cutoff value of 6.01, elevated NLR was independently associated with the presence of R‐DWILs (OR = 3.170, 95% CI 1.306‐7.697, P = .011) in the bivariate logistic regression analysis with adjustment for age, sex, atrial fibrillation, previous ischemic stroke/TIA, SBP on admission, hematoma volume, and IVH. Conclusions This study provides significant evidence of the association between circulating NLR and R‐DWILs in spontaneous ICH patients. Patients with NLR > 6.01 at 24‐48 hours after ICH ictus should be paid more attention to when evaluating R‐DWILs.

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Section: P-valuementioning

confidence: 51%

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 76%

Section: P-valuementioning

confidence: 99%

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Early elevated neutrophil‐to‐lymphocyte ratio associated with remote diffusion‐weighted imaging lesions in acute intracerebral hemorrhage

Chen

et al. 2019

CNS Neurosci Ther

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“…The process of NET release, or ‘NETosis’, was first characterised as a ‘last‐ditch’ neutrophil response to the presence of bacteria in the bloodstream (Brinkmann et al , ). NETosis represents a complex antibacterial response in which neutrophils release their nuclear contents, often in the process of dying, to capture and immobilise bacteria and other toxins in the bloodstream (McDonald et al , ; Kimball et al , ; Pfeiler et al , ). However, NET formation is also toxic to the surrounding vasculature and collateral endothelial injury from NETs is strongly associated with vascular dysfunction (Xu et al , ).…”

Section: How Do Circulating Blood Cells Contribute To Vte Development?mentioning

confidence: 99%

Advances in understanding the molecular mechanisms of venous thrombosis

2019

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Summary Venous thromboembolism (VTE) represents a leading cause of global mortality, however, the determinants that contribute to thrombus development remain incompletely understood. In this review, we discuss the role of inherited abnormalities of blood coagulation in VTE pathogenesis. In addition, we also consider recent emerging data suggesting other molecular and cellular determinants may also contribute. Specifically, we describe the role played by the inflamed endothelium, and the dysregulated responses to inflammatory stimuli that create a platform for pathological clot formation. We review the accumulating evidence that blood cells, contact pathway factors and protein disulphide isomerases all play key roles in VTE development. Finally, we discuss new insights into the role of metabolites arising from commensal gut bacteria and their potential role in facilitating VTE. This overview provides an update on these state‐of‐the‐art developments and the opportunities they provide for new antithrombotic therapies with enhanced efficacy and improved safety profiles.

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Polymerized Salicylic Acid Microparticles Reduce the Progression and Formation of Human Neutrophil Extracellular Traps (NET)s

Brannon,

Piegols,

Cady

et al. 2024

Adv Healthcare Materials

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Neutrophils can contribute to inflammatory disease propagation via innate mechanisms intended for inflammation resolution. For example, neutrophil extracellular traps (NETs) are necessary for trapping pathogens but can contribute to clot formation and blood flow restriction, that is, ischemia. Currently, no therapeutics in the clinic directly target NETs despite the known involvement of NETs contributing to mortality and increased disease severity. Vascular‐deployed particle‐based therapeutics are a novel and robust alternative to traditional small‐molecule drugs by enhancing drug delivery to cells of interest. This work designs a high‐throughput assay to investigate the immunomodulatory behavior and functionality of salicylic acid‐based polymer‐based particle therapeutics against NETosis in human neutrophils. Briefly, this work finds that polymeric composition plays a role, and particle size can also influence rates of NETosis. Salicylate‐based polymeric (Poly‐SA) particles are found to functionally inhibit NETosis depending on the particle size and concentration exposed to neutrophils. This work demonstrates the high throughput method can help fast‐track particle‐based therapeutic optimization and design, more efficiently preparing this innovative therapeutics for the clinic.

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Propagation of thrombosis by neutrophils and extracellular nucleosome networks

Abstract: © Ferrata Storti FoundationActivation of intravascular blood coagulation and the formation of thrombi in microvessels (microvascular thrombosis) under certain conditions support a distinct mechanism of intravascular immunity named immunothrombosis.

Cited by 108 publications

References 78 publications

Early elevated neutrophil‐to‐lymphocyte ratio associated with remote diffusion‐weighted imaging lesions in acute intracerebral hemorrhage

Early elevated neutrophil‐to‐lymphocyte ratio associated with remote diffusion‐weighted imaging lesions in acute intracerebral hemorrhage

Advances in understanding the molecular mechanisms of venous thrombosis

Polymerized Salicylic Acid Microparticles Reduce the Progression and Formation of Human Neutrophil Extracellular Traps (NET)s

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