基于血浆的检测可区分创伤性凝血病中的高纤维蛋白溶解和失代偿亚组。
Plasma-based assays distinguish hyperfibrinolysis and shutdown subgroups in trauma-induced coagulopathy.
机构信息
From the Department of Surgery (M.A.L., N.E.D., K.F.), University of Vermont, Burlington, Vermont; Department of Pathology and Laboratory Medicine and UNC Blood Research Center (L.A.H., A.S.W.), University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Pharmacology (G.H.), University of Vermont, Burlington, Vermont; Synapse Research Institute (B.D.L.), Maastricht, the Netherlands; Department of Surgery (H.B.M., E.E.M., M.J.C.), University of Colorado School of Medicine (E.E.M.), Aurora; Ernest E Moore Shock Trauma Center at Denver Health (E.E.M.), Denver, Colorado; and Department of Biochemistry and Laboratory for Clinical Biochemistry Research (B.A.B.), University of Vermont, Burlington, Vermont.
出版信息
J Trauma Acute Care Surg. 2022 Nov 1;93(5):579-587. doi: 10.1097/TA.0000000000003723. Epub 2022 Jun 10.
BACKGROUND
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.
METHODS
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. Noninjured 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).
RESULTS
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 with 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. Tissue plasminogen activator-stimulated plasmin generation was similar in hyperfibrinolysis and shutdown samples. Differences in LY30, fibrin structure, and lysis correlated with pH.
CONCLUSION
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.
LEVEL OF EVIDENCE
Prognostic/Epidemiological; Level III.
背景
纤维蛋白溶解异常的创伤患者发病率和死亡率增加。了解区分纤维蛋白溶解表型的机制对于优化治疗非常重要。我们假设通过全血粘弹性测量确定纤维蛋白溶解异常的患者也可以通过血浆凝血酶生成、血栓结构、纤维蛋白形成和纤溶酶生成测量来区分。
方法
研究了由全血血栓弹性描记术定义的纤维蛋白溶解抑制（30 分钟时的溶解率 [LY30] <0.9，n=11）或高纤维蛋白溶解（LY30>3%，n=9）的观察性横断面创伤队列的血小板缺乏性血浆（PPP）。非损伤对照提供了比较样本。通过荧光、共焦显微镜、浊度和荧光校准的纤溶酶测定分别测量凝血酶生成、纤维蛋白结构和形成以及纤溶酶生成，在不存在/存在组织因子或组织型纤溶酶原激活物（tPA）的情况下。
结果
尽管在对照 PPP 中未检测到自发凝血酶生成，但在高纤维蛋白溶解或抑制患者的 PPP 中检测到自发凝血酶生成，并且高纤维蛋白溶解组的延迟时间比抑制组短。添加组织因子掩盖了这种差异，但在高纤维蛋白溶解样本中发现了更多的凝血酶生成。与抑制相比，高纤维蛋白溶解 PPP 形成更密集的纤维蛋白网络。在不存在 tPA 的情况下，抑制比高纤维蛋白溶解 PPP 的纤维蛋白形成速度更快，但高纤维蛋白溶解凝块自发溶解；这些差异在添加 tPA 时被掩盖。高纤维蛋白溶解和抑制 PPP 样本中的组织型纤溶酶原激活物刺激的纤溶酶生成相似。LY30、纤维蛋白结构和溶解的差异与 pH 值相关。
结论
本研究使用 PPP 为基础的测定方法发现，高纤维蛋白溶解和抑制亚组在凝血酶生成、纤维蛋白形成和结构以及溶解方面存在差异。这些组在促进 tPA 触发的纤溶酶生成方面没有差异。在 PPP 中描述这些活性的能力促进了识别促进创伤不良结局的机制的研究。
证据水平
预后/流行病学；三级。
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