Tan Avalene W K, Li Ronald H L, Ueda Yu, Stern Joshua A, Hussain Mehrab, Haginoya Satoshi, Sharpe Ashely N, Gunther-Harrington Catherine T, Epstein Steven E, Nguyen Nghi
William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis, Davis, CA, United States.
Front Vet Sci. 2022 Jul 14;9:892377. doi: 10.3389/fvets.2022.892377. eCollection 2022.
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.
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.
野火对人类、野生动物和家畜构成重大健康风险。我们之前发现，自然发生烟雾吸入和热烧伤的家猫与有类似损伤的人类之间存在病理生理相似性；其特征为短暂性心肌增厚、心肌肌钙蛋白I升高以及心内血栓形成。虽然潜在机制尚不清楚，但小鼠模型的结果表明，血小板预激活和激活可能导致全身高凝状态和血栓形成。在此，我们评估并比较了29只自然发生野火热损伤（WF）的猫、21只患有亚临床肥厚型心肌病（HCM）的临床健康猫和11只无HCM的健康猫（CC）的血小板激活程度、血小板对生理激动剂的反应以及血小板衍生微泡（PDMV）水平。我们还对WF猫和CC猫的循环PDMV进行了定量和比较。此外，我们研究了暴露于野火的猫的血栓形成事件、烧伤严重程度、心肌变化与血小板激活程度之间的关联。流式细胞术检测血小板表面P-选择素表达显示，与两个对照组相比，WF猫对二磷酸腺苷（ADP）和凝血酶的血小板反应增强，表明循环中存在预激活血小板。此外，WF组猫的循环PDMV水平升高，其特征是外膜上磷脂酰丝氨酸增加。记录有心内血栓形成的WF组猫在存在ADP的情况下血小板激活和血小板预激活升高。虽然高剂量花生四烯酸（AA）大多导致血小板抑制，但在有心内血栓形成的WF组猫中观察到对AA的持续反应。单因素和多因素逻辑回归分析表明，血小板对AA反应增强与血栓形成事件独立相关。这是第一项报告自然发生与野火相关损伤和烟雾吸入的家猫中血小板预激活与心内血栓形成之间显著关联的研究。
在一群家猫中，自然发生野火烟雾暴露和热烧伤后，由于血小板预激活，出现了血小板激活和血小板衍生微泡脱落。
