Department of Emergency Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Bloodworks Research Institute, Seattle, WA, USA.
J Thromb Haemost. 2021 Jul;19(7):1666-1675. doi: 10.1111/jth.15316. Epub 2021 Apr 18.
Coagulopathic bleeding is a major cause of mortality after trauma, and platelet dysfunction contributes to this problem. The causes of platelet dysfunction are relatively unknown, but a great deal can be learned from the plasma environment about the possible pathways involved.
Describe the changes in plasma proteomic profile associated with platelet dysfunction after trauma.
Citrated blood was collected from severely injured trauma patients at the time of their arrival to the Emergency Department. Samples were collected from 110 patients, and a subset of twenty-four patients was identified by a preserved (n = 12) or severely impaired (n = 12) platelet aggregation response to five different agonists. Untargeted proteomics was performed by nanoflow liquid chromatography tandem mass spectrometry. Protein abundance levels for each patient were normalized to total protein concentration to control for hemodilution by crystalloid fluid infusion prior to blood draw.
Patients with platelet dysfunction were more severely injured but otherwise demographically similar to those with retained platelet function. Of 232 proteins detected, twelve were significantly different between groups. These proteins fall into several broad categories related to platelet function, including microvascular obstruction with platelet activation, immune activation, and protease activation.
This observational study provides a description of the change in proteomic profile associated with platelet dysfunction after trauma and identifies twelve proteins with the most profound changes. The pathways involving these proteins are salient targets for immediate investigation to better understand platelet dysfunction after trauma and identify targets for intervention.
凝血功能障碍性出血是创伤后死亡的主要原因，血小板功能障碍是导致这种情况的原因之一。血小板功能障碍的原因尚不清楚，但可以从血浆环境中了解到涉及的可能途径。
描述与创伤后血小板功能障碍相关的血浆蛋白质组特征变化。
在急诊科采集严重创伤患者的枸橼酸盐血液。共采集了 110 例患者的样本，其中 24 例患者根据血小板聚集对五种不同激动剂的反应（保存良好[n=12]或严重受损[n=12]）分为亚组。通过纳流液相色谱串联质谱进行非靶向蛋白质组学分析。为了控制采血前晶体液输注引起的血液稀释，将每位患者的蛋白丰度水平与总蛋白浓度进行归一化。
血小板功能障碍患者的损伤更为严重，但在其他方面与血小板功能保留患者相似。在检测到的 232 种蛋白质中，有 12 种在两组之间存在显著差异。这些蛋白质分为几个与血小板功能相关的广泛类别，包括血小板激活的微血管阻塞、免疫激活和蛋白酶激活。
这项观察性研究描述了创伤后与血小板功能障碍相关的蛋白质组特征变化，并确定了 12 种变化最明显的蛋白质。涉及这些蛋白质的途径是立即进行研究以更好地了解创伤后血小板功能障碍并确定干预靶点的重要目标。
