COVID-19 and Sepsis Are Associated With Different Abnormalities in Plasma Procoagulant and Fibrinolytic Activity.
COVID-19 and Sepsis Are Associated With Different Abnormalities in Plasma Procoagulant and Fibrinolytic Activity.
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DOI：
10.1161/atvbaha.120.315338
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发表时间：
2021-01
期刊：
影响因子：
--
通讯作者：
Campbell RA
中科院分区：
文献类型：
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作者：
Bouck EG;Denorme F;Holle LA;Middelton EA;Blair AM;de Laat B;Schiffman JD;Yost CC;Rondina MT;Wolberg AS;Campbell RA
新冠肺炎与凝血和内皮功能的生物标志物紊乱有关，并被比作脓毒症的凝血障碍。然而，临床实验室指标显示了这些病理上的关键差异。我们试图确定与健康供者和患有脓毒症的危重患者相比，新冠肺炎患者的血浆凝血和纤溶潜力是否不同。我们对99名住院患者(46名新冠肺炎患者，53名脓毒症患者)和18名健康献血员进行了单中心横断面观察研究，并进行了血浆对比研究。我们用免疫测定法测定内源性凝血和纤溶活性的生物标志物，用荧光法测定凝血酶和纤溶酶的生成能力，用浊度测定纤维蛋白的形成和溶解。与健康献血者相比，新冠肺炎或脓毒症患者的纤维蛋白原、D-二聚体、可溶性血栓调节蛋白和纤溶酶-抗纤溶酶复合体均升高。尽管预防性抗凝，新冠肺炎患者的凝血酶生成潜力仍有增加，而脓毒症患者则没有。新冠肺炎患者的血浆内源性纤溶酶潜力也增加，而脓毒症患者的血浆纤溶酶生成延迟。血浆凝血酶和纤溶酶生成的集体紊乱使新冠肺炎和脓毒症患者的纤维蛋白生成增加。出乎意料的是，新冠肺炎患者凝血酶、纤溶酶和纤维蛋白形成的滞后时间随着疾病严重程度的增加而延长，这表明重症新冠肺炎伴随着凝血启动机制的丧失。新冠肺炎和脓毒症都与内源性凝血和纤溶激活有关，但这两种疾病对血浆促凝血和纤溶能力的影响不同。促凝血和纤溶通路的失调可能在新冠肺炎和脓毒症的病理生理机制中起独特作用。
COVID-19 is associated with derangement in biomarkers of coagulation and endothelial function and has been likened to the coagulopathy of sepsis. However, clinical laboratory metrics suggest key differences in these pathologies. We sought to determine if plasma coagulation and fibrinolytic potential in patients with COVID-19 differ compared to healthy donors and critically-ill patients with sepsis. We performed comparative studies on plasmas from a single-center, cross-sectional observational study of 99 hospitalized patients (46 with COVID-19, 53 with sepsis) and 18 healthy donors. We measured biomarkers of endogenous coagulation and fibrinolytic activity by immunoassays, thrombin and plasmin generation potential by fluorescence, and fibrin formation and lysis by turbidity. Compared to healthy donors, patients with COVID-19 or sepsis both had elevated fibrinogen, D-dimer, soluble thrombomodulin, and plasmin-antiplasmin complexes. Patients with COVID-19 had increased thrombin generation potential despite prophylactic anticoagulation, whereas patient with sepsis did not. Plasma from patients with COVID-19 also had increased endogenous plasmin potential, whereas patients with sepsis showed delayed plasmin generation. The collective perturbations in plasma thrombin and plasmin generation permitted enhanced fibrin formation in both COVID-19 and sepsis. Unexpectedly, the lag times to thrombin, plasmin, and fibrin formation were prolonged with increased disease severity in COVID-19, suggesting a loss of coagulation-initiating mechanisms accompanies severe COVID-19. Both COVID-19 and sepsis are associated with endogenous activation of coagulation and fibrinolysis, but these diseases differently impact plasma procoagulant and fibrinolytic potential. Dysregulation of procoagulant and fibrinolytic pathways may uniquely contribute to the pathophysiology of COVID-19 and sepsis.