Endotheliopathy is Associated with a 24-hour Fibrinolysis Phenotype Described by Low TEG Lysis and High D-Dimer after Trauma: a Secondary Analysis of the PROPPR Study.
Endotheliopathy is Associated with a 24-hour Fibrinolysis Phenotype Described by Low TEG Lysis and High D-Dimer after Trauma: a Secondary Analysis of the PROPPR Study.
复制标题
内皮病与创伤后低 TEG 裂解和高 D-二聚体描述的 24 小时纤溶表型相关：PROPPR 研究的二次分析。
DOI：
10.1097/as9.0000000000000116
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Richter,JillianR
中科院分区：
文献类型：
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作者：
Richter,RobertP;Joiner,DanielleM;Griffin,RussellL;Jansen,JanO;Kerby,JeffreyD;Wade,CharlesE;Holcomb,JohnB;Cardenas,JessicaC;Richter,JillianR
目的：确定内皮病变的生物标志物、24小时纤溶表型和创伤后临床结局之间的相关性。背景：血管内皮是止血和器官功能的重要调节因子。内皮病变和纤维蛋白溶解的标志物之间的关系还没有evaluated.Methods：我们进行了二次分析的前瞻性收集的生物标志物数据的实用随机最佳血小板和血浆比例（PROPPR）随机对照试验。我们通过24小时血栓弹力图（TEG）、血栓溶解百分比（LY 30）和血浆d-二聚体（DD）水平对受试者进行分层，并评估了具有以下四种24小时纤溶表型之一的受试者之间内皮病生物标志物和临床结局的差异：结果：LY 30正常组168例，LY 30高组32例，LY 30低+ DD低组147例，LY 30低+DD高组124例。与其他表型相比，LY 30低+ DD高受试者的损伤严重程度更高，严重脑损伤、多器官功能衰竭（MOF）和死亡率的发生率更高。所有内皮病生物标志物在LY 30低+ DD高表型中显著更高。调整损伤严重程度、机制和头部创伤后，24小时血管生成素-2和可溶性血栓调节蛋白与LY 30低+ DD高表型独立相关。两种内皮生物标志物均能区分MOF。血栓调节蛋白水平> 9.5 ng/mL和血管生成素-2水平> 3.6 ng/mL的受试者占64%的受试者发展MOF.Conclusions：在多中心创伤队列中，具有纤溶表型特征的受试者在损伤后24小时具有低TEG溶解和升高的DD，其内皮病变和临床结局显著更差。我们的研究结果支持机制评估的作用，内皮细胞在纤溶失调，可能会推动后期organ injury.Mini-abstract：这项回顾性研究评估了内皮病变的生物标志物，24小时纤溶表型和创伤后的临床结局之间的关联。损伤后24小时，具有以低TEG溶解和升高的d-二聚体水平为特征的纤维蛋白溶解表型的受试者具有显著更差的内皮病变和临床结局。血管生成素-2和血栓调节蛋白的循环水平被确定为内皮生物标志物，具有鉴别多器官衰竭的潜在效用。
Objectives:Determine associations between biomarkers of endotheliopathy, 24-hour fibrinolysis phenotypes and clinical outcomes after trauma.Background: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.Methods: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% to 2.9%(LY30 norm), LY30> 2.9%(LY30 high), LY30< 0.9% and low DD (LY30 low+ DD low), and LY30< 0.9% and high DD (LY30 low+ DD high).Results:The analysis included 168 subjects with LY30 norm, 32 with LY30 high, 147 with LY30 low+ DD low, and 124 with LY30 low+ DD high. LY30 low+ DD high 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 low+ DD high phenotype. Adjusting for injury severity, mechanism, and head trauma, 24-hour angiopoietin-2 and soluble thrombomodulin were independently associated with the LY30 low+ DD high 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.Conclusions: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.Mini-abstract: This retrospective study evaluated the associations between endotheliopathy biomarkers, 24-hour fibrinolysis phenotypes and clinical outcomes after trauma. Subjects with a fibrinolysis phenotype characterized by low TEG lysis and elevated d-dimer levels 24 hours after injury had significantly worse endotheliopathy and clinical outcomes. Circulating levels of angiopoietin-2 and thrombomodulin were identified as endothelial biomarkers with potential utility for discriminating multiorgan failure.