From the Departments of Surgery (A.B., C.C.S., E.E.M., M.K., A.S., E.G., H.B.M., E.P., B.E.H., P.E., J.C., A.G.), Pediatrics (C.C.S., K.J.), Biochemistry and Molecular Genetics (A.D'A., K.H.), and Radiology (M.P.C.), School of Medicine, University of Colorado Denver, Aurora, CO; Research Laboratory (C.C.S., M.K.), Bonfils Blood Center, Denver, CO; and the Department of Surgery (E.E.M., M.D., A.S., E.G., H.B.M., B.E.H, P.E., J.C., A.G.), Denver Health Medical Center, Denver, CO.
J Trauma Acute Care Surg. 2018 Jun;84(6):929-938. doi: 10.1097/TA.0000000000001878.
Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology.
Blood samples were collected in the field or at emergency department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), "eufibrinolytic" (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins.
HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared with healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p < 0.005). The other 16 decreased proteins indicate activation of the alternate complement pathway, depletion of carrier proteins, and four glycoproteins. CXC7 was elevated in all injured patients versus healthy controls (p < 0.005), and 35 proteins were unchanged across all groups (p > 0.1 and fold change of concentrations of 0.75-1.3).
HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times, or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs.
Prognostic, level III.
止血的黏弹性测量表明，20%的严重受伤患者存在全身性过度纤溶，早期死亡率增加。这些患者的凝块形成正常，但快速发生凝块溶解。本研究应用靶向蛋白质组学来定量分析过度纤溶患者的血浆蛋白，以阐明潜在的病理生理学机制。
在现场或急诊科到达时采集血液样本，并使用血栓弹力图（TEG）来表征在天然和组织型纤溶酶原激活物（tPA）刺激条件下体外的凝块形成。从表现出正常 30 分钟（Ly30）纤溶时间的受伤患者中采集了 10 个样本（“正常纤溶”（EF）），从 HF 患者中采集了 10 个样本，定义为 tPA 刺激的 TEG Ly30 >50%，从健康对照中采集了 10 个样本。通过靶向蛋白质组学和 ELISA 检测分析创伤患者样本中特定的凝血蛋白。
HF 患者表现出纤溶酶原激活增加。与健康对照组和 EF 患者相比，HF 患者有 33 种蛋白质显著减少；其中 17 种是具有抗蛋白酶消耗的凝血蛋白（p < 0.005）。其他 16 种减少的蛋白质表明替代补体途径的激活、载体蛋白的消耗以及四种糖蛋白。所有受伤患者的 CXC7 均高于健康对照组（p < 0.005），而所有组之间的 35 种蛋白质没有变化（p > 0.1，浓度变化倍数为 0.75-1.3）。
HF 患者存在特定蛋白质的显著减少，支持创伤引起的过度纤溶中的已知机制，也出乎意料地减少了凝血因子 II、X 和 XIII，而凝块形成（SP、R 时间或角度）没有变化。HF 患者的凝块稳定性降低与 tPA 刺激的 TEG 相符。
预后，III 级。
