Department of Surgery, Zuckerberg San Francisco General Hospital and the University of California, San Francisco, San Francisco, California, USA.
Department of Medicine, University of California, San Francisco, San Francisco, California, USA.
J Thromb Haemost. 2022 Sep;20(9):2109-2118. doi: 10.1111/jth.15763. Epub 2022 May 30.
Impaired ex vivo platelet aggregation is common in trauma patients. The mechanisms driving these impairments remain incompletely understood, but functional platelet exhaustion due to excessive in vivo activation is implicated. Given platelet adrenoreceptors and known catecholamine surges after injury, impaired ex vivo platelet aggregation in trauma patients may be linked to catecholamine-induced functional platelet exhaustion.
To determine the relationship of catecholamines with platelet-dependent hemostasis after injury and to model catecholamine-induced functional platelet exhaustion in healthy donor platelets.
PATIENTS/METHODS: Whole blood was collected from 67 trauma patients as part of a prospective cohort study. Platelet aggregometry and rotational thromboelastometry were performed, and plasma epinephrine (EPI) and norepinephrine (NE) concentrations were measured. The effect of catecholamines on healthy donor platelets was examined in a microfluidic model, with platelet aggregometry, and by flow cytometry examining surface markers of platelet activation.
In trauma patients, EPI and NE were associated with impaired platelet aggregation (both p < 0.05), and EPI was additionally associated with decreased viscoelastic clot strength, increased fibrinolysis, and mortality (all p < 0.05). In healthy donors, short duration incubation with EPI enhanced platelet aggregation, platelet adhesion under flow, and increased glycoprotein IIb/IIIa activation, while weaker effects were observed with NE. Compared with short incubation, longer incubation with EPI resulted in decreased platelet adhesion, platelet aggregation, and surface expression of glycoprotein IIb/IIIa.
These findings suggest sympathoadrenal activation in trauma patients contributes to impaired ex vivo platelet aggregation, which mechanistically may be explained by a functionally exhausted platelet phenotype under prolonged exposure to high plasma catecholamine levels.
创伤患者常存在体外血小板聚集受损。导致这些损伤的机制尚不完全清楚，但推测与体内过度激活导致的功能性血小板耗竭有关。鉴于血小板肾上腺素能受体和损伤后已知的儿茶酚胺激增，创伤患者体外血小板聚集受损可能与儿茶酚胺诱导的功能性血小板耗竭有关。
确定儿茶酚胺与损伤后血小板依赖性止血之间的关系，并在健康供体血小板中模拟儿茶酚胺诱导的功能性血小板耗竭。
患者/方法：作为前瞻性队列研究的一部分，从 67 名创伤患者中采集全血。进行血小板聚集测定和旋转血栓弹性测定，并测量血浆肾上腺素（EPI）和去甲肾上腺素（NE）浓度。在微流控模型中检查儿茶酚胺对健康供体血小板的影响，并用血小板聚集测定和流式细胞术检查血小板活化的表面标志物。
在创伤患者中，EPI 和 NE 与血小板聚集受损相关（均 p < 0.05），EPI 还与粘弹性凝块强度降低、纤溶增加和死亡率增加相关（均 p < 0.05）。在健康供体中，EPI 短时间孵育可增强血小板聚集、血小板在流动下的黏附以及糖蛋白 IIb/IIIa 的激活，而 NE 的作用较弱。与短孵育相比，EPI 长时间孵育导致血小板黏附、血小板聚集和糖蛋白 IIb/IIIa 表面表达减少。
这些发现表明，创伤患者的交感肾上腺激活导致体外血小板聚集受损，其机制可能是由于在长时间暴露于高血浆儿茶酚胺水平下，血小板表现出功能耗竭。
