{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T10:40:57Z","timestamp":1788950457288,"version":"build-2803163510"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016512","name":"Center for Companion Animal Health, University of California, Davis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016512","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>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 (WF), 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 WF cats had increased platelet response to adenosine diphosphate (ADP) and thrombin compared to the two 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. While high dose arachidonic acid (AA) mostly resulted in platelet inhibition, persistent 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.<\/jats:p><jats:sec><jats:title>One Sentence Summary<\/jats:title><jats:p>Platelet activation and shedding of platelet-derived microvesicles due to platelet priming is present following naturally occurring wildfire smoke exposure and thermal burn injuries in a population of domestic cats.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fvets.2022.892377","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T06:42:27Z","timestamp":1657780947000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Platelet Priming and Activation in Naturally Occurring Thermal Burn Injuries and Wildfire Smoke Exposure Is Associated With Intracardiac Thrombosis and Spontaneous Echocardiographic Contrast in Feline Survivors"],"prefix":"10.3389","volume":"9","author":[{"given":"Avalene W. K.","family":"Tan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald H. L.","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Ueda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua A.","family":"Stern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehrab","family":"Hussain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Haginoya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashely N.","family":"Sharpe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine T.","family":"Gunther-Harrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Epstein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nghi","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1038\/s41598-020-59497-z","article-title":"& Stern JA. Cats with thermal burn injuries from California wildfires show echocardiographic evidence of myocardial thickening and intracardiac thrombi","volume":"10","author":"Sharpe","year":"2020","journal-title":"Sci Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"e007492","DOI":"10.1161\/JAHA.117.007492","article-title":"Cardiovascular and cerebrovascular emergency department visits associated with wildfire smoke exposure in California in 2015","volume":"7","author":"Wettstein","year":"2018","journal-title":"J Am Heart Assoc"},{"key":"B3","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1016\/j.scitotenv.2017.12.086","article-title":"Wildland fire smoke and human health","volume":"624","author":"Cascio","year":"2018","journal-title":"Sci Total Environ."},{"key":"B4","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12940-016-0093-4","article-title":"& Rappold AG. Repeating cardiopulmonary health effects in rural North Carolina population during a second large peat wildfire","volume":"15","author":"Tinling","year":"2016","journal-title":"Environ Health."},{"key":"B5","doi-asserted-by":"publisher","first-page":"e001653","DOI":"10.1161\/JAHA.114.001653","article-title":"Impact of fine particulate matter (PM2.5) exposure during wildfires on cardiovascular health outcomes","volume":"4","author":"Haikerwal","year":"2015","journal-title":"J Am Heart Assoc."},{"key":"B6","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1097\/SHK.0000000000001484","article-title":"Burn-induced coagulopathies: a comprehensive review","volume":"54","author":"Ball","year":"2020","journal-title":"Shock"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1016\/j.burns.2016.05.001","article-title":"Upon admission coagulation and platelet function in patients with thermal and electrical injuries","volume":"42","author":"Wade","year":"2016","journal-title":"Burns."},{"key":"B8","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.burns.2018.09.020","article-title":"Thrombin generation in patients with severe thermal injury","volume":"45","author":"Wiegele","year":"2018","journal-title":"Burns."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/09537104.2018.1448379","article-title":"Activation, function and content of platelets in burn patients","volume":"30","author":"Marck","year":"2018","journal-title":"Platelets."},{"key":"B10","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1097\/SHK.0b013e3182837831","article-title":"Lan YT. A novel model of burn-blast combined injury and its phasic changes of blood coagulation in rats","volume":"40","author":"Chai","year":"2013","journal-title":"Shock."},{"key":"B11","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1097\/SHK.0000000000000460","article-title":"Goodman MD. Impact of platelets and platelet-derived microparticles on hypercoagulability following burn injury","volume":"45","author":"Midura","year":"2016","journal-title":"Shock."},{"key":"B12","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1177\/1753425918789255","article-title":"Start a fire, kill the bug: The role of platelets in inflammation and infection","volume":"24","author":"Deppermann","year":"2018","journal-title":"Innate Immun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1161\/CIRCRESAHA.117.310795","article-title":"Circulating platelets as mediators of immunity, inflammation, and thrombosis","volume":"122","author":"Koupenova","year":"2018","journal-title":"Circ Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1055\/s-2005-916671","article-title":"Platelets: physiology and biochemistry","volume":"31","author":"Jurk","year":"2005","journal-title":"Semin Thromb Hemost."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.3389\/fimmu.2019.01731","article-title":"Langer HF. Platelets and immune responses during thromboinflammation","volume":"10","author":"Mezger","year":"2019","journal-title":"Front Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1097\/SHK.0000000000000974","article-title":"Platelet-derived microvesicles: a potential therapy for trauma-induced coagulopathy","volume":"49","author":"Lopez","year":"2018","journal-title":"Shock."},{"key":"B17","doi-asserted-by":"publisher","first-page":"267","DOI":"10.3109\/08958370903278069","article-title":"Exposure of mice to concentrated ambient particulate matter results in platelet and systemic cytokine activation","volume":"22","author":"Wilson","year":"2010","journal-title":"Inhal Toxicol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1161\/01.ATV.17.4.646","article-title":"Sakariassen KS. Shear-induced platelet activation and platelet microparticle formation at blood flow conditions as in arteries with a severe stenosis","volume":"17","author":"Holme","year":"1997","journal-title":"Arterioscl Thrombosis Vasc Biol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1111\/jvim.12325","article-title":"Kittleson MD. Platelet activation in cats with hypertrophic cardiomyopathy","volume":"28","author":"Tablin","year":"2014","journal-title":"J Vet Int Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1111\/jvim.14568","article-title":"Platelet activation and clopidogrel effects on ADP-induced platelet activation in cats with or without the A31P mutation in MYBPC3","volume":"30","author":"Li","year":"2016","journal-title":"J Vet Int Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"S244","DOI":"10.1016\/j.jvc.2015.03.008","article-title":"Cardiomyopathy prevalence in 780 apparently healthy cats in rehoming centres (the CatScan study)","volume":"17","author":"Payne","year":"2015","journal-title":"J Vet Cardiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.jvc.2004.11.001","article-title":"Doppler echocardiographic assessment of left atrial appendage flow velocities in normal cats","volume":"7","author":"Schober","year":"2005","journal-title":"J Vet Cardiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s12917-019-1997-3","article-title":"Canine platelets express functional Toll-like receptor-4: lipopolysaccharide-triggered platelet activation is dependent on adenosine diphosphate and thromboxane A2 in dogs","volume":"15","author":"Li","year":"2019","journal-title":"BMC Vet Res."},{"key":"B24","doi-asserted-by":"publisher","first-page":"267","DOI":"10.3389\/fvets.2020.00267","article-title":"Assessment of P2Y12 inhibition by clopidogrel in feline platelets using flow cytometry quantification of vasodilator-stimulated phosphoprotein phosphorylation","volume":"7","author":"Li","year":"2020","journal-title":"Front Vet Sci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"95","DOI":"10.3109\/08958378.2016.1145771","article-title":"Naeher LP. Review of the health effects of wildland fire smoke on wildland firefighters and the public","volume":"28","author":"Adetona","year":"2016","journal-title":"Inhal Toxicol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1289\/ehp.1409277","article-title":"Elliott CT. Critical review of health impacts of wildfire smoke exposure","volume":"124","author":"Reid","year":"2016","journal-title":"Environ Health Perspect."},{"key":"B27","doi-asserted-by":"publisher","first-page":"037006","DOI":"10.1289\/EHP3860","article-title":"Cardiopulmonary effects of fine particulate matter exposure among older adults, during wildfire and non-wildfire periods, in the United States 2008\u20132010","volume":"127","author":"DeFlorio-Barker","year":"2019","journal-title":"Environ Health Perspect."},{"key":"B28","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1289\/ehp.1408436","article-title":"Tonkin AM. Forest fire smoke exposures and out-of-hospital cardiac arrests in melbourne, australia: a case-crossover study","volume":"123","author":"Dennekamp","year":"2015","journal-title":"Environ Health Persp."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1289\/ehp.1003206","article-title":"Peat bog wildfire smoke exposure in rural North Carolina is associated with cardiopulmonary emergency department visits assessed through syndromic surveillance","volume":"119","author":"Rappold","year":"2011","journal-title":"Environ Health Persp"},{"key":"B30","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1136\/oem.2008.041376","article-title":"The relationship of respiratory and cardiovascular hospital admissions to the southern California wildfires of 200","volume":"66","author":"Delfino","year":"2009","journal-title":"Occup Environ Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.tips.2008.05.002","article-title":"& Momi S. Potentiation and priming of platelet activation: a potential target for antiplatelet therapy","volume":"29","author":"Gresele","year":"2008","journal-title":"Trends Pharmacol Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1160\/TH12-03-0161","article-title":"Thrombogenic changes in young and old mice upon subchronic exposure to air pollution in an urban roadside tunnel","volume":"108","author":"Emmerechts","year":"2012","journal-title":"Thromb Haemost."},{"key":"B33","unstructured":"Air Quality Summary for 2018 and 2018-2019 Check Before You Light Program Summary"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1111\/j.1538-7836.2009.03348.x","article-title":"Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation","volume":"7","author":"Lupia","year":"2009","journal-title":"J Thromb Haemost."},{"key":"B35","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.burns.2003.12.006","article-title":"Grimm D. Vascular endothelial growth factor serum level is strongly enhanced after burn injury and correlated with local and general tissue edema","volume":"30","author":"Infanger","year":"2004","journal-title":"Burns."},{"key":"B36","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1097\/BCR.0b013e31820aafcf","article-title":"Changes in cardiac physiology after severe burn injury","volume":"32","author":"Williams","year":"2011","journal-title":"J Burn Care Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.toxlet.2015.03.005","article-title":"TCDD and omeprazole prime platelets through the aryl hydrocarbon receptor (AhR) non-genomic pathway","volume":"235","author":"Pombo","year":"2015","journal-title":"Toxicol Lett."},{"key":"B38","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1002\/jat.3554","article-title":"Lipopolysaccharide levels adherent to PM25 play an important role in particulate matter induced-immunosuppressive effects in mouse splenocytes","volume":"38","author":"He","year":"2018","journal-title":"J Appl Toxicol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"11027","DOI":"10.1038\/s41598-017-11471-y","article-title":"Urban PM25 exacerbates allergic inflammation in the murine lung via a TLR2\/TLR4\/MyD88-signaling pathway","volume":"7","author":"He","year":"2017","journal-title":"Sci Rep."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1948","DOI":"10.1007\/s10753-020-01269-y","article-title":"PM25 exposure induces inflammatory response in macrophages via the TLR4\/COX-2\/NF-\u03baB pathway","volume":"43","author":"Fu","year":"2020","journal-title":"Inflammation."},{"key":"B41","doi-asserted-by":"publisher","first-page":"S150","DOI":"10.1093\/jbcr\/irz013.258","article-title":"The role of inflammation, platelets, and microparticles\/nanoparticles in burn wounds","volume":"40","author":"Schmidt","year":"2019","journal-title":"J Burn Care Res"},{"key":"B42","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.thromres.2018.09.047","article-title":"Geiger J. Multifaceted effects of arachidonic acid and interaction with cyclic nucleotides in human platelets","volume":"171","author":"Rukoyatkina","year":"2018","journal-title":"Thromb Res."},{"key":"B43","first-page":"279","article-title":"Platelet inhibitory receptors","author":"Nagy","year":"2019"},{"key":"B44","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1177\/1040638715584994","article-title":"Assessment of platelet function in healthy sedated cats using three whole blood platelet function tests","volume":"27","author":"Ho","year":"2015","journal-title":"J Vet Diagn Invest."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2704","DOI":"10.1182\/blood.V82.9.2704.bloodjournal8292704","article-title":"& Gresele P. Prostaglandin E2 potentiates platelet aggregation by priming protein kinase C","volume":"82","author":"Vezza","year":"1993","journal-title":"Blood."},{"key":"B46","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1172\/JCI10881","article-title":"Koller BH. Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation","volume":"107","author":"Fabre","year":"2001","journal-title":"J Clin Invest."},{"key":"B47","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1111\/j.1939-165X.2007.tb00203.x","article-title":"Evaluation of coagulation markers in the plasma of healthy cats and cats with asymptomatic hypertrophic cardiomyopathy","volume":"36","author":"B\u00e9dard","year":"2007","journal-title":"Vet Clin Path."},{"key":"B48","doi-asserted-by":"publisher","first-page":"S306","DOI":"10.1016\/j.jvc.2015.10.004","article-title":"Secondary prevention of cardiogenic arterial thromboembolism in the cat: The double-blind, randomized, positive-controlled feline arterial thromboembolism; clopidogrel vs. aspirin trial (FAT CAT)","volume":"1","author":"Hogan","year":"2015","journal-title":"J Vet Cardiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1111\/jvim.15745","article-title":"ACVIM consensus statement guidelines for the classification, diagnosis, and management of cardiomyopathies in cats","volume":"34","author":"Luis Fuentes","year":"2020","journal-title":"J Vet Intern Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/09537104.2016.1265924","article-title":"Platelet microvesicles in health and disease","volume":"28","author":"Melki","year":"2017","journal-title":"Platelets."},{"key":"B51","doi-asserted-by":"publisher","first-page":"13397","DOI":"10.1038\/s41598-019-49635-7","article-title":"Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes","volume":"9","author":"Ivanov","year":"2019","journal-title":"Sci Rep-uk."},{"key":"B52","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1160\/TH14-12-1067","article-title":"& Storey R. The role of platelets in inflammation","volume":"114","author":"Thomas","year":"2015","journal-title":"Thromb Haemostasis."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1111\/j.1538-7836.2007.02557.x","article-title":"Hoylaerts MF. Enhanced peripheral thrombogenicity after lung inflammation is mediated by platelet\u2013leukocyte activation: role of P-selectin","volume":"5","author":"Nemmar","year":"2007","journal-title":"J Thromb Haemost."},{"key":"B54","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1097\/TA.0b013e3182984911","article-title":"Hypercoagulability after burn injury","volume":"75","author":"Van Haren","year":"2013","journal-title":"J Trauma Acute Care Surg."}],"container-title":["Frontiers in Veterinary Science"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.892377\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T06:42:48Z","timestamp":1657780968000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fvets.2022.892377\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,14]]},"references-count":54,"alternative-id":["10.3389\/fvets.2022.892377"],"URL":"https:\/\/doi.org\/10.3389\/fvets.2022.892377","relation":{},"ISSN":["2297-1769"],"issn-type":[{"value":"2297-1769","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,14]]},"article-number":"892377"}}