Canine Neutrophil Extracellular Traps Enhance Clot Formation and Delay Lysis

Jeffery, Unity; LeVine, Dana N.

doi:10.1177/0300985817699860

Cited by 24 publications

(18 citation statements)

References 32 publications

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“…Thrombosis is commonly encountered in critically ill small animals and causes substantial morbidity and mortality . Thrombosis contributes to morbidity and mortality through promotion of inflammation and through direct end‐organ damage . Thrombosis complicates the management of multiple disease processes and is the primary cause of various veterinary emergency room visits .…”

Section: Introductionmentioning

confidence: 99%

American College of Veterinary Emergency and Critical Care (ACVECC) Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines: Small animal

Goggs

Blais

Brainard

et al. 2019

J Vet Emergen Crit Care

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Objectives: To systematically review available evidence and establish guidelines related to the risk of developing thrombosis and the management of small animals with antithrombotics. Design: Standardized, systematic evaluation of the literature (identified by searching Medline via PubMed and CAB abstracts) was carried out in 5 domains (Defining populations at risk; Defining rational therapeutic use; Defining evidence-based protocols; Refining and monitoring antithrombotic therapies; and Discontinuing antithrombotic therapies). Evidence evaluation was carried out using Population, Intervention, Comparison, Outcome generated within each domain questions to address specific aims. This was followed by categorization of relevant articles according to level of evidence and quality (Good, Fair, or Poor). Synthesis of these data led to the development of a series of statements. Consensus on the final guidelines was achieved via Delphi-style surveys.Draft recommendations were presented at 2 international veterinary conferences and made available for community assessment, review, and comment prior to final revisions and publication. Settings: Academic and referral veterinary medical centers.Results: Over 500 studies were reviewed in detail. Worksheets from all 5 domains generated 59 statements with 83 guideline recommendations that were refined during 3 rounds of Delphi surveys. A high degree of consensus was reached across all guideline recommendations. Conclusions:Overall, systematic evidence evaluations yielded more than 80 recommendations for the treatment of small animals with or at risk of developing thrombosis. Numerous significant knowledge gaps were highlighted by the evidence reviews undertaken, indicating the need for substantial additional research in this field. K E Y W O R D S ) for their dedicated contributions to this effort. We would also like to thank the members of the veterinary community who attended and contributed to the discussion of the guidelines during the 2018 EVECC Congress and IVECCS sessions and subsequently during the online open-comment stages. CONFLICT OF INTERESTThe authors declare that they have no conflicts of interest.

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Section: Introductionmentioning

confidence: 99%

American College of Veterinary Emergency and Critical Care (ACVECC) Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines: Small animal

Goggs

Blais

Brainard

et al. 2019

J Vet Emergen Crit Care

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“…Since the study showed elevated levels of circulating nucleosome, a marker for immune-mediated haemolytic anaemia (IMHA), the authors hypothesised a contribution of NETs in the mortality of this disease; although they argued that their results should be viewed with caution due to the low number of patients [3]. The same group recently analysed the involvement of NETs in clot formation [75]. They suggested that NET proteins and DNA contribute to thrombosis in inflammatory diseases.…”

Section: Extracellular Traps In Carnivores Such As Felidae Canidae mentioning

confidence: 99%

“…Their study showed that NETs increased the maximum clot formation velocity and delayed lysis. DNAse treatment reduced the effect on the clot lysis, but not on the formation velocity, indicating an involvement of NET associated proteins [75]. It was hypothesised that NET proteins interact with the early components of the coagulation cascade; thus, canine NETs can be used as markers of thrombotic risk [75].…”

Section: Extracellular Traps In Carnivores Such As Felidae Canidae mentioning

confidence: 99%

“…DNAse treatment reduced the effect on the clot lysis, but not on the formation velocity, indicating an involvement of NET associated proteins [75]. It was hypothesised that NET proteins interact with the early components of the coagulation cascade; thus, canine NETs can be used as markers of thrombotic risk [75]. To detect the DNA fibres in canine plasma, the commonly used SytoxGreen DNA-quantification assay [141] was compared with a DNA/histone ELISA [142].…”

Section: Extracellular Traps In Carnivores Such As Felidae Canidae mentioning

confidence: 99%

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Extracellular Traps: An Ancient Weapon of Multiple Kingdoms

Neumann

Brogden²,

Köckritz-Blickwede

2020

Biology

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The discovery, in 2004, of extracellular traps released by neutrophils has extended our understanding of the mode of action of various innate immune cells. This fascinating discovery demonstrated the extracellular trapping and killing of various pathogens by neutrophils. During the last decade, evidence has accumulated showing that extracellular traps play a crucial role in the defence mechanisms of various cell types present in vertebrates, invertebrates, and plants. The aim of this review is to summarise the relevant literature on the evolutionary history of extracellular traps used as a weapon in various kingdoms of life. Biology 2020, 9, 34 2 of 23On the basis of findings from several studies mostly performed with human and murine neutrophils, the following three different pathways that lead to the formation of ETs by innate immune cells have been identified: (1) Release of nuclear DNA by ETosis, a suicidal cell death associated with the rupture of the nuclear membrane prior to cell lysis [14,15]; (2) vesicular release of nuclear DNA by viable cells [16,17]; and (3) release of mitochondrial DNA [18,19]. However, the exact molecular mechanisms leading to one or the other phenotype of ET formation has still not been entirely clarified. A group of renowned scientists and experts on NETs has recently published an opinionated review on the subject due to the abundance of available data that has also led to some confusion in the NET/ET research community because of contradictory results and divergent scientific concepts, for example, the molecular pathways of ET formation or the origin of the DNA that forms the ET scaffold [20]. There is a strong consensus about the composition of ETs among the findings that NETs contain a high amount of granule proteins, for example, cell-type-specific proteases and other antibacterial molecules that are associated with DNA-histone complexes. However, it is still unclear how different triggers or pathways have led to phenotypical differences about the source of DNA or viability of the ET-releasing cell.Comparison of ET phenotypical differences between host species in relation to evolutionary aspects, especially by comparing data from phylogenetic groups, would help to understand the pathways of ET formation in more detail.

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“…Advanced DIC in septic patients usually presents as hemorrhage or multiple organ failure. Recent evidence in humans and dogs demonstrates that NETs and their components can exacerbate DIC by directly enhancing ex vivo clot formation, activating platelets, as well as, inhibiting anticoagulant pathways ( 76 – 78 ). Observational studies have shown that human or canine septic patients have aberrant amounts of circulating cell-free DNA (cfDNA), which can influence the dynamics of thrombus formation in several ways ( 12 , 79 ).…”

Section: Detrimental Role Of Nets In Sepsismentioning

confidence: 99%

A Comparative Review of Neutrophil Extracellular Traps in Sepsis

Tablin

2018

Front. Vet. Sci.

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Sepsis is the leading cause of critical illness and mortality in human beings and animals. Neutrophils are the primary effector cells of innate immunity during sepsis. Besides degranulation and phagocytosis, neutrophils also release neutrophil extracellular traps (NETs), composed of cell-free DNA, histones, and antimicrobial proteins. Although NETs have protective roles in the initial stages of sepsis, excessive NET formation has been found to induce thrombosis and multiple organ failure in murine sepsis models. Since the discovery of NETs nearly a decade ago, many investigators have identified NETs in various species. However, many questions remain regarding the exact mechanisms and fate of neutrophils following NET formation. In humans and mice, platelet-neutrophil interactions via direct binding or soluble mediators seem to play an important role in mediating NET formation during sepsis. Preliminary data suggest that these interactions may be species dependent. Regardless of these differences, there is increasing evidence in human and veterinary medicine suggesting that NETs play a crucial role in the pathogenesis of intravascular thrombosis and multiple organ failure in sepsis. Because the outcome of sepsis is highly dependent on early recognition and intervention, detection of NETs or NET components can aid in the diagnosis of sepsis in humans and veterinary species. In addition, the use of novel therapies such as deoxyribonuclease and non-anticoagulant heparin to target NET components shows promising results in murine septic models. Much work is needed in translating these NET-targeting therapies to clinical practice.

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Canine Neutrophil Extracellular Traps Enhance Clot Formation and Delay Lysis

Cited by 24 publications

References 32 publications

American College of Veterinary Emergency and Critical Care (ACVECC) Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines: Small animal

American College of Veterinary Emergency and Critical Care (ACVECC) Consensus on the Rational Use of Antithrombotics in Veterinary Critical Care (CURATIVE) guidelines: Small animal

Extracellular Traps: An Ancient Weapon of Multiple Kingdoms

A Comparative Review of Neutrophil Extracellular Traps in Sepsis

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