Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion.
Proteomics of Coagulopathy Following Injury Reveals Limitations of Using Laboratory Assessment to Define Trauma-Induced Coagulopathy to Predict Massive Transfusion.
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损伤后凝血病的蛋白质组学揭示了使用实验室评估来定义创伤引起的凝血病以预测大量输血的局限性。
DOI：
10.1097/as9.0000000000000167
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Wisniewski,Stephen
中科院分区：
文献类型：
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作者：
Moore,HunterB;Neal,MatthewD;Bertolet,Marnie;Joughin,BrianA;Yaffe,MichaelB;Barrett,ChristopherD;Bird,MollyA;Tracy,RussellP;Moore,ErnestE;Sperry,JasonL;Zuckerbraun,BrianS;Park,MyungS;Cohen,MitchellJ;Wisniewski,Stephen
目的：创伤性凝血病（TIC）是由多种机制引起的，被认为是大量输血（MT）的驱动因素之一。使用凝血酶原时间（INR）或血栓弹力图（TEG）的单一实验室值用于临床定义这一复杂过程。我们使用了蛋白质组学的方法来测试目前的定义TIC（国际标准化比值，TEG，或临床判断）是否足以捕捉大多数与MT相关的蛋白质变化。方法：8个I级创伤中心提供的血液样本，从受伤后早期可用的患者。TIC定义为INR> 1.5（INR-TIC）、TEG最大振幅< 50 mm（TEG-TIC）或创伤外科医生的临床判断（Clin-TIC）。MT定义为24小时内> 10单位红细胞或前4小时内> 4单位RBC/小时。对1305种蛋白质进行了SomaLogic蛋白质组学分析。与蛋白质失调的患者与每个TIC定义和MT的途径进行了identified.Results：患者（n= 211）的平均损伤严重程度评分为24，MT和死亡率分别为22%和12%。我们在MT患者中鉴定了578种SOMAscan分析物失调，其中INR-TIC、TEG-TIC和Clin-TIC患者分别仅在25%、3%和4%中显示失调。TIC定义未能显示73%与MT相关的蛋白质水平的变化，并且未能识别26%接受大量输血的患者。INR-TIC和TEG-TIC患者显示与补体活性显著相关的蛋白质失调。蛋白质失调临床TIC或大量输血患者没有显着相关的任何pathway.Conclusion：这些数据表明，有未探索的机会，以确定患者的大出血的风险。在仅基于实验室测量或临床评估定义TIC的患者中，接受MT的患者中仅一小部分失调的蛋白质在统计学上显著失调。
Objective:Trauma-induced coagulopathy (TIC) is provoked by multiple mechanisms and is perceived to be one driver of massive transfusions (MT). Single laboratory values using prothrombin time (INR) or thrombelastography (TEG) are used to clinically define this complex process. We used a proteomics approach to test whether current definitions of TIC (INR, TEG, or clinical judgment) are sufficient to capture the majority of protein changes associated with MT.Methods:Eight level I trauma centers contributed blood samples from patients available early after injury. TIC was defined as INR> 1.5 (INR-TIC), TEG maximum amplitude< 50 mm (TEG-TIC), or clinical judgment (Clin-TIC) by the trauma surgeon. MT was defined as> 10 units of red blood cells in 24 hours or> 4 units RBC/hour during the first 4 hours. SomaLogic proteomic analysis of 1305 proteins was performed. Pathways associated with proteins dysregulated in patients with each TIC definition and MT were identified.Results:Patients (n= 211) had a mean injury severity score of 24, with a MT and mortality rate of 22% and 12%, respectively. We identified 578 SOMAscan analytes dysregulated among MT patients, of which INR-TIC, TEG-TIC, and Clin-TIC patients showed dysregulation only in 25%, 3%, and 4% of these, respectively. TIC definitions jointly failed to show changes in 73% of the protein levels associated with MT, and failed to identify 26% of patients that received a massive transfusion. INR-TIC and TEG-TIC patients showed dysregulation of proteins significantly associated with complement activity. Proteins dysregulated in Clin-TIC or massive transfusion patients were not significantly associated with any pathway.Conclusion:These data indicate there are unexplored opportunities to identify patients at risk for massive bleeding. Only a small subset of proteins that are dysregulated in patients receiving MT are statistically significantly dysregulated among patients whose TIC is defined based solely on laboratory measurements or clinical assessment.