Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.
Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.
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DOI：
10.1097/aln.0000000000004239
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发表时间：
2022-07-01
期刊：
影响因子：
8.8
通讯作者：
Sullenger, Bruce A.
中科院分区：
文献类型：
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作者：
Corey, Kristin M.;Olson, Lyra B.;Naqvi, Ibtehaj A.;Morrison, Sarah A.;Davis, Connor;Nimjee, Shahid M.;Que, Loretta G.;Bachelder, Robin E.;Kraft, Bryan D.;Chen, Lingye;Nair, Smita K.;Levy, Jerrold H.;Sullenger, Bruce A.
COVID-19导致高凝状态，但重症患者凝血功能障碍与低氧血症之间的关系尚未得到彻底探讨。我们假设凝血功能障碍的严重程度与需要ICU水平护理的患者的ARDS严重程度、主要血栓事件和死亡率相关。于2020年4月至2020年10月期间，在这项针对重症COVID-19患者的前瞻性观察性队列研究中进行了ROTEM粘弹性测试和凝血因子生物标志物分析。进行统计学分析，以确定显著的凝血病生物标志物，如纤维蛋白溶解抑制型纤溶酶原激活物抑制剂-1（派-1）及其与临床结局的相关性，如死亡率、体外膜肺氧合（ECMO）要求、重大血栓形成事件的发生和低氧血症的严重程度（根据柏林标准，PaO 2/FiO 2分为轻度、中度和重度）。总的来说，53/55（96%）的队列需要机械通气，9/55（16%）需要ECMO。ECMO初治患者在ROTEM上显示30分钟时的溶解指数指示纤维蛋白溶解抑制。存活者表现出更少的促凝急性期反应物，如MP-组织因子水平（OR 0.14（0.02，0.99），p = 0.049）。与发生出血事件的患者相比，未发生出血事件的患者ADAMTS 13水平变化较小（OR 0.05（0，.7），p = 0.026）。在发生重大血栓事件的ECMO初治患者中，也证实派-1（OR 1.95（1.21，3.14），p = 0.006）、d-二聚体（OR 3.52（0.99，12.48），p = 0.05）和因子VIII（无凝块1.15 ± 0.28 vs凝块1.42 ± 0.31，p = 0.003）升高。与轻度和中度ARDS相比，重度ARDS期间派-1水平显著升高（重度44.2 ± 14.9 ng/mL vs轻度31.8 ± 14.7 ng/mL和中度33.1 ± 15.9 ng/mL，分别为p = 0.029和0.039）。炎性和促凝血标志物（如派-1、MP-组织因子、vWF水平）升高与重度低氧血症和重大血栓形成事件相关，涉及微循环系统中的纤维蛋白溶解抑制以及重度COVID-19中随后的微血管和大血管血栓形成。
COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. We hypothesized that severity of coagulopathy would be associated with ARDS severity, major thrombotic events, and mortality in patients requiring ICU-level care. Viscoelastic testing by ROTEM 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 (PAI-1) and their associations with clinical outcomes such as mortality, extracorporeal membrane oxygenation (ECMO) requirement, occurrence of major thrombotic events, and severity of hypoxemia (PaO2/FiO2 categorized into mild, moderate, and severe per the Berlin Criteria). In total, 53/55 (96%) of the cohort required mechanical ventilation and 9/55 (16%) required ECMO. ECMO-naïve patients demonstrated Lysis Indices at 30 minutes indicative of fibrinolytic suppression on ROTEM. Survivors demonstrated less procoagulate acute phase reactants such as MP-Tissue Factor levels (OR 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 that did (OR 0.05 (0, .7), p = 0.026). Elevations in PAI-1 (OR 1.95 (1.21, 3.14), p = 0.006), d-dimer (OR 3.52 (0.99, 12.48), p = 0.05), and factor VIII (no clot 1.15 ± 0.28 versus clot 1.42 ± 0.31, p = 0.003) were also demonstrated in ECMO-naïve patients who experienced major thrombotic events. PAI-1 levels were significantly elevated during periods of severe compared to mild and moderate ARDS (severe 44.2 ± 14.9 ng/mL versus mild 31.8 ± 14.7 ng/mL and moderate 33.1 ± 15.9 ng/mL, p = 0.029 and 0.039 respectively). Increased inflammatory and pro-coagulant markers such as PAI-1, MP- Tissue Factor, vWF 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.