Richter Robert P, Joiner Danielle M, Griffin Russell L, Jansen Jan O, Kerby Jeffrey D, Wade Charles E, Holcomb John B, Cardenas Jessica C, Richter Jillian R
Division of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama, USA.
Ann Surg Open. 2022 Mar;3(1). doi: 10.1097/as9.0000000000000116.
Determine associations between biomarkers of endotheliopathy, 24-hour fibrinolysis phenotypes and clinical outcomes after trauma.
The vascular endothelium is a critical regulator of hemostasis and organ function. The relationship between markers of endotheliopathy and fibrinolysis following trauma has not been evaluated.
We performed a secondary analysis of prospectively collected biomarker data in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized controlled trial. We stratified subjects by 24-hour thromboelastography (TEG) percent clot lysis (LY30) and plasma D-dimer (DD) levels and evaluated differences in endotheliopathy biomarkers and clinical outcomes between subjects with one of four 24-hour fibrinolysis phenotypes: LY30 0.9-2.9% (LY30), LY30 >2.9% (LY30), LY30 <0.9% and low DD (LY30+DD), and LY30 <0.9% and high DD (LY30+DD).
The analysis included 168 subjects with LY30, 32 with LY30, 147 with LY30+DD and 124 with LY30+DD. LY30+DD subjects had greater injury severity and a higher incidence of severe head injury, multiorgan failure (MOF), and mortality than the other phenotypes. All endotheliopathy biomarkers were significantly higher in the LY30+DD phenotype. Adjusting for injury severity, mechanism and head trauma, 24-hour angiopoietin-2 and soluble thrombomodulin were independently associated with the LY30+DD phenotype. Both endothelial biomarkers were discriminating for MOF. Subjects with thrombomodulin level >9.5 ng/mL and angiopoietin-2 level >3.6 ng/mL accounted for 64% of subjects who developed MOF.
In a multicenter trauma cohort, subjects with a fibrinolysis phenotype characterized by low TEG lysis and elevated DD 24 hours after injury have significantly worse endotheliopathy and clinical outcomes. Our findings support mechanistic evaluations of the role of the endothelium in fibrinolysis dysregulation that may drive late-stage organ injury.
确定内皮病变生物标志物、24小时纤维蛋白溶解表型与创伤后临床结局之间的关联。
血管内皮是止血和器官功能的关键调节因子。创伤后内皮病变标志物与纤维蛋白溶解之间的关系尚未得到评估。
我们对实用随机最佳血小板与血浆比例（PROPPR）随机对照试验中前瞻性收集的生物标志物数据进行了二次分析。我们根据24小时血栓弹力图（TEG）的血块溶解百分比（LY30）和血浆D-二聚体（DD）水平对受试者进行分层，并评估具有四种24小时纤维蛋白溶解表型之一的受试者在内皮病变生物标志物和临床结局方面的差异：LY30 0.9 - 2.9%（LY30）、LY30 >2.9%（LY30）、LY30 <0.9%且DD低（LY30+DD），以及LY30 <0.9%且DD高（LY30+DD）。
分析纳入了168例LY30受试者、32例LY30受试者、147例LY30+DD受试者和124例LY30+DD受试者。与其他表型相比，LY30+DD受试者的损伤严重程度更高，严重颅脑损伤、多器官功能衰竭（MOF）和死亡率的发生率更高。所有内皮病变生物标志物在LY30+DD表型中均显著更高。在调整损伤严重程度、机制和颅脑创伤后，24小时血管生成素-2和可溶性血栓调节蛋白与LY30+DD表型独立相关。两种内皮生物标志物对MOF均具有鉴别意义。血栓调节蛋白水平>9.5 ng/mL且血管生成素-2水平>3.6 ng/mL的受试者占发生MOF受试者的64%。
在一个多中心创伤队列中，损伤后24小时具有TEG溶解低和DD升高特征的纤维蛋白溶解表型的受试者，其内皮病变和临床结局明显更差。我们的研究结果支持对内皮在可能导致晚期器官损伤的纤维蛋白溶解失调中所起作用进行机制评估。
