Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy.
Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy.
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DOI：
10.1097/ta.0000000000003723
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发表时间：
2022-11-01
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纤溶异常的创伤患者的发病率和死亡率都有所增加。了解纤溶表型的区别机制对于优化治疗非常重要。我们假设，通过全血粘弹性测定法确定的纤溶异常的受试者也可以通过血浆凝血酶生成、凝块结构、纤维蛋白形成和纤溶酶生成的测量来区分。观察创伤横断面队列中纤溶停止(30分钟%溶解[LY30]和0.9，N=11)或纤溶亢进(LY30和GT；3%，N=9)的全血血栓弹性图示的贫血小板血浆(PPP)。非损伤对照受试者提供了对照样本。在没有/存在组织因子或组织纤溶酶原激活物(TPA)的情况下，分别用荧光、共聚焦显微镜、浊度和荧光校准纤溶酶分析法检测凝血酶生成、纤维蛋白结构和形成以及纤溶酶生成。正常对照组的PPP未检测到自发凝血酶生成，纤溶亢进或停机患者的PPP有自发凝血酶生成，且纤溶亢进时的滞后时间比停机时短。组织因子的加入掩盖了这一差异，但在纤溶亢进样本中显示凝血酶生成增加。与关闭相比，纤溶亢进的PPP形成了更致密的纤维蛋白网络。在没有tPA的情况下，停机状态下纤维蛋白的形成速度比纤溶亢进快，但纤溶亢进的凝块会自发溶解；这些差异被tPA的加入所掩盖。TPA刺激的纤溶酶生成在纤溶亢进和停机样本中相似。LY30、纤维蛋白结构和裂解作用的差异与pH有关。这项基于PPP的探索性研究确定了纤溶亢进和关闭亚组在凝血酶生成、纤维蛋白形成和结构以及溶解方面的差异。这些组在促进tPA触发的纤溶酶生成方面没有区别。在PPP中表征这些活动的能力有助于研究确定促进创伤不良后果的机制。
Trauma patients with abnormal fibrinolysis have increased morbidity and mortality. Knowledge of mechanisms differentiating fibrinolytic phenotypes is important to optimize treatment. We hypothesized that subjects with abnormal fibrinolysis identified by whole blood viscoelastometry can also be distinguished by plasma thrombin generation, clot structure, fibrin formation, and plasmin generation measurements. Platelet-poor plasma (PPP) from an observational cross-sectional trauma cohort with fibrinolysis shutdown (% lysis at 30 minutes [LY30]<0.9, N=11) or hyperfibrinolysis (LY30>3%, N=9) defined by whole blood thromboelastography were studied. Non-injured control subjects provided comparative samples. Thrombin generation, fibrin structure and formation, and plasmin generation were measured by fluorescence, confocal microscopy, turbidity, and a fluorescence-calibrated plasmin assay, respectively, in the absence/presence of tissue factor or tissue plasminogen activator (tPA). Whereas spontaneous thrombin generation was not detected in PPP from control subjects, PPP from hyperfibrinolysis or shutdown patients demonstrated spontaneous thrombin generation, and the lag time was shorter in hyperfibrinolysis versus shutdown. Addition of tissue factor masked this difference but revealed increased thrombin generation in hyperfibrinolysis samples. Compared to shutdown, hyperfibrinolysis PPP formed denser fibrin networks. In the absence of tPA, the fibrin formation rate was faster in shutdown than hyperfibrinolysis, but hyperfibrinolysis clots lysed spontaneously; these differences were masked by addition of tPA. TPA-stimulated plasmin generation was similar in hyperfibrinolysis and shutdown samples. Differences in LY30, fibrin structure, and lysis correlated with pH. This exploratory study using PPP-based assays identified differences in thrombin generation, fibrin formation and structure, and lysis in hyperfibrinolysis and shutdown subgroups. These groups did not differ in their ability to promote tPA-triggered plasmin generation. The ability to characterize these activities in PPP facilitates studies to identify mechanisms that promote adverse outcomes in trauma.