BACKGROUND COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respiratory distress syndrome severity, major thrombotic events, and mortality in patients requiring intensive care unit-level care. METHODS Viscoelastic testing by rotational thromboelastometry and coagulation factor biomarker analyses were performed in this prospective observational cohort study of critically ill COVID-19 patients from April 2020 to October 2020. Statistical analyses were performed to identify significant coagulopathic biomarkers such as fibrinolysis-inhibiting plasminogen activator inhibitor 1 and their associations with clinical outcomes such as mortality, extracorporeal membrane oxygenation requirement, occurrence of major thrombotic events, and severity of hypoxemia (arterial partial pressure of oxygen/fraction of inspired oxygen categorized into mild, moderate, and severe per the Berlin criteria). RESULTS In total, 53 of 55 (96%) of the cohort required mechanical ventilation and 9 of 55 (16%) required extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation-naïve patients demonstrated lysis indices at 30 min indicative of fibrinolytic suppression on rotational thromboelastometry. Survivors demonstrated fewer procoagulate acute phase reactants, such as microparticle-bound tissue factor levels (odds ratio, 0.14 [0.02, 0.99]; P = 0.049). Those who did not experience significant bleeding events had smaller changes in ADAMTS13 levels compared to those who did (odds ratio, 0.05 [0, 0.7]; P = 0.026). Elevations in plasminogen activator inhibitor 1 (odds ratio, 1.95 [1.21, 3.14]; P = 0.006), d-dimer (odds ratio, 3.52 [0.99, 12.48]; P = 0.05), and factor VIII (no clot, 1.15 ± 0.28 vs. clot, 1.42 ± 0.31; P = 0.003) were also demonstrated in extracorporeal membrane oxygenation-naïve patients who experienced major thrombotic events. Plasminogen activator inhibitor 1 levels were significantly elevated during periods of severe compared to mild and moderate acute respiratory distress syndrome (severe, 44.2 ± 14.9 ng/ml vs. mild, 31.8 ± 14.7 ng/ml and moderate, 33.1 ± 15.9 ng/ml; P = 0.029 and 0.039, respectively). CONCLUSIONS Increased inflammatory and procoagulant markers such as plasminogen activator inhibitor 1, microparticle-bound tissue factor, and von Willebrand factor levels are associated with severe hypoxemia and major thrombotic events, implicating fibrinolytic suppression in the microcirculatory system and subsequent micro- and macrovascular thrombosis in severe COVID-19. EDITOR’S PERSPECTIVE

中文翻译：

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COVID-19 患者纤维蛋白溶解和高凝状态、低氧血症严重程度和死亡率的抑制：一项回顾性队列研究。

背景 COVID-19 会导致高凝状态，但危重患者凝血障碍与低氧血症之间的关联尚未得到彻底探讨。这项研究假设，凝血功能障碍的严重程度与需要重症监护病房级别护理的患者的急性呼吸窘迫综合征严重程度、主要血栓事件和死亡率相关。方法 在这项针对 2020 年 4 月至 2020 年 10 月危重 COVID-19 患者的前瞻性观察队列研究中，通过旋转血栓弹力测定法进行粘弹性测试和凝血因子生物标志物分析。进行统计分析以识别重要的凝血病生物标志物，例如纤维蛋白溶解抑制型纤溶酶原激活剂抑制剂1 及其与临床结果的关联，例如死亡率、体外膜氧合需求、主要血栓事件的发生以及低氧血症的严重程度（动脉氧分压/吸入氧分数，根据柏林标准分为轻度、中度和重度） 。结果 总共 55 人中有 53 人 (96%) 需要机械通气，55 人中有 9 人 (16%) 需要体外膜肺氧合。首次进行体外膜肺氧合的患者在 30 分钟时表现出溶解指数，表明旋转血栓弹力图显示纤溶抑制。幸存者表现出较少的促凝急性期反应物，例如微粒结合的组织因子水平（比值比，0.14 [0.02，0.99]；P = 0.049）。与那些经历过重大出血事件的人相比，那些没有经历过重大出血事件的人的 ADAMTS13 水平变化较小（比值比，0.05 [0, 0.7]；P = 0.026）。纤溶酶原激活剂抑制剂 1（优势比，1.95 [1.21, 3.14]；P = 0.006）、d-二聚体（优势比，3.52 [0.99, 12.48]；P = 0.05）和因子 VIII（无凝块，1.15 ± 0.28 vs. 血栓，1.42 ± 0.31；P = 0.003）也在经历过重大血栓事件的体外膜氧合初治患者中得到证实。与轻度和中度急性呼吸窘迫综合征相比，重度期间纤溶酶原激活剂抑制剂 1 水平显着升高（重度为 44.2 ± 14.9 ng/ml，轻度为 31.8 ± 14.7 ng/ml，中度为 33.1 ± 15.9 ng/ml； P 分别 = 0.029 和 0.039）。结论 纤溶酶原激活物抑制剂 1、微粒结合组织因子和血管性血友病因子水平等炎症和促凝血标记物水平升高与严重低氧血症和主要血栓事件相关，表明严重时微循环系统中的纤溶抑制以及随后的微血管和大血管血栓形成2019冠状病毒病。编辑的观点