Impact of Platelets and Platelet-Derived Microparticles on Hypercoagulability Following Burn Injury

Kuethe, Joshua W.; Rice, Teresa C.; Veile, Rosalie; England, Lisa G.; Friend, Lou Ann; Caldwell, Charles C.; Goodman, Michael D.

doi:10.1097/shk.0000000000000460

Cited by 26 publications

(14 citation statements)

References 39 publications

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“…In the present study we did not evaluate platelet-derived MVs, because our primary focus was to investigate the roles of MVs in the acute inflammatory response, rather than coagulopathy. Hypercoagulability is an important component of severe burns pathophysiology, and indeed a recent animal study using mice has reported acute increases in circulating pro-coagulant platelet-derived MVs following a scalding injury [23]. However, coagulopathy may not be yet present at patient admission as part of the acute trauma response [24, 25] and therefore temporally distinct from acute onset SIRS.…”

Section: Discussionmentioning

confidence: 99%

Circulating Microvesicles Are Elevated Acutely following Major Burns Injury and Associated with Clinical Severity

et al. 2016

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Microvesicles are cell-derived signaling particles emerging as important mediators and biomarkers of systemic inflammation, but their production in severe burn injury patients has not been described. In this pilot investigation, we measured circulating microvesicle levels following severe burns, with severe sepsis patients as a comparator group. We hypothesized that levels of circulating vascular cell-derived microvesicles are elevated acutely following burns injury, mirroring clinical severity due to the early onset and prevalence of systemic inflammatory response syndrome (SIRS) in these patients. Blood samples were obtained from patients with moderate to severe thermal injury burns, with severe sepsis, and from healthy volunteers. Circulating microvesicles derived from total leukocytes, granulocytes, monocytes, and endothelial cells were quantified in plasma by flow cytometry. All circulating microvesicle subpopulations were elevated in burns patients on day of admission (day 0) compared to healthy volunteers (leukocyte-microvesicles: 3.5-fold, p = 0.005; granulocyte-microvesicles: 12.8-fold, p<0.0001; monocyte-microvesicles: 20.4-fold, p<0.0001; endothelial- microvesicles: 9.6-fold, p = 0.01), but decreased significantly by day 2. Microvesicle levels were increased with severe sepsis, but less consistently between patients. Leukocyte- and granulocyte-derived microvesicles on day 0 correlated with clinical assessment scores and were higher in burns ICU non-survivors compared to survivors (leukocyte MVs 4.6 fold, p = 0.002; granulocyte MVs 4.8 fold, p = 0.003). Mortality prediction analysis of area under receiver operating characteristic curve was 0.92 (p = 0.01) for total leukocyte microvesicles and 0.85 (p = 0.04) for granulocyte microvesicles. These findings demonstrate, for the first time, acute increases in circulating microvesicles following burns injury in patients and point to their potential role in propagation of sterile SIRS-related pathophysiology.

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Section: Discussionmentioning

confidence: 99%

Circulating Microvesicles Are Elevated Acutely following Major Burns Injury and Associated with Clinical Severity

et al. 2016

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“…Recent studies showed that, in human serum, most EVs are P-EVs, although EVs can also be generated from white blood cells and cancer cells 15 - 17 . P-EVs have been found to participate in a variety of important biological and pathological processes via intracellular communication 18 , 19 , including clotting 20 , 21 , angiogenesis 22 , 23 , inflammation 24 , 25 , immunoregulation 3 , cellular prion protein transport 26 , and tumor progression 25 , 27 .…”

Section: Introductionmentioning

confidence: 99%

Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach

2017

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Extracellular vesicles (EVs) are a newly-discovered way by which cells communicate with their neighbors, as well as transporting cargos which once were considered to be limited by membrane barriers, including membrane proteins, cytosolic proteins and RNA. The discovery of platelet-derived EVs (P-EVs), the most abundant EVs in human blood, has been a very tortuous process. At first, P-EVs were identified as nothing but 'platelet dust', and subsequent research did not progress smoothly because of the limited research techniques to study EVs. Following leaps and bounds of technical progress in studying EVs, more and more attractive features of P-EVs were revealed and they began to be further researched. The aim of this review is to present the latest knowledge about the role of P-EVs in tissue repair and tumor progression. The potential mechanism of P-EVs is emphasized. Then the limitations of the present study and future research directions are discussed.

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“…Observational studies in humans and murine models of burn injuries describe an initial hypercoagulable state despite the presence of thrombocytopenia [6][7][8][9] . This nding suggests that systemic platelet activation, which likely precedes platelet consumption, plays a crucial role in mediating hypercoagulability as a result of burn injuries 7,10,11 . Although the exact mechanisms of increased platelet activation in these patients are unknown, endothelial stress and injury during in ammation may facilitate platelet rolling and activation, and subsequent platelet-immune cell interactions via toll-like receptors (TLR) fueling further in ammation [12][13][14][15] .…”

Section: Introductionmentioning

confidence: 97%

Platelet Priming Following Naturally Occurring Thermal Burn Injuries And Wildfire Smoke Exposure is Associated with Intracardiac Thrombosis in Feline Survivors

Li¹,

Tan²,

Ueda³

et al. 2021

Preprint

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Wildfires pose a major health risk for humans, wildlife, and domestic animals. We previously discovered pathophysiologic parallels between domestic cats with naturally occurring smoke inhalation and thermal burn injuries and human beings with similar injuries; these were characterized by transient myocardial thickening, cardiac troponin I elevation and formation of intracardiac thrombosis. While the underlying mechanisms remain unclear, results from murine models suggest that platelet priming and activation may contribute to a global hypercoagulable state and thrombosis. Herein, we evaluated and compared the degree of platelet activation, platelet response to physiologic agonists and levels of platelet-derived microvesicles (PDMV) in 29 cats with naturally occurring wildfire thermal injuries, 21 clinically healthy cats with subclinical hypertrophic cardiomyopathy (HCM) and 11 healthy cats without HCM (CC). We also quantified and compared circulating PDMVs in WF cats to CC cats. In addition, we examined the association between thrombotic events, severity of burn injuries, myocardial changes, and the degree of platelet activation in cats exposed to wildfires. Flow cytometric detection of platelet surface P-selectin expression showed that cats in the wildfire group (WF) had increased platelet response to adenosine diphosphate (ADP) and thrombin compared to the 2 control groups indicating the presence of primed platelets in circulation. In addition, cats in the WF group had increased circulating levels of PDMV, characterized by increased phosphatidylserine on the external leaflet. Cats in the WF group with documented intracardiac thrombosis had elevated platelet activation and platelet priming in the presence of ADP or thrombin. While high dose arachidonic acid (AA) mostly resulted in platelet inhibition, persistent platelet activation in response to AA was noted among cats in the WF group with intracardiac thrombosis. Univariate and multiple logistic regression analyses demonstrated that increased platelet response to AA was independently associated with thrombotic events. This is the first study reporting the significant association between platelet priming and intracardiac thrombosis in domestic cats with naturally occurring wildfire-related injuries and smoke inhalation. Further studies are required to delineate additional mechanisms between inflammation and thrombosis, especially regarding platelet primers and the cyclooxygenase pathway.

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Impact of Platelets and Platelet-Derived Microparticles on Hypercoagulability Following Burn Injury

Cited by 26 publications

References 39 publications

Circulating Microvesicles Are Elevated Acutely following Major Burns Injury and Associated with Clinical Severity

Circulating Microvesicles Are Elevated Acutely following Major Burns Injury and Associated with Clinical Severity

Platelet-derived Extracellular Vesicles: An Emerging Therapeutic Approach

Platelet Priming Following Naturally Occurring Thermal Burn Injuries And Wildfire Smoke Exposure is Associated with Intracardiac Thrombosis in Feline Survivors

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