von Meijenfeldt Fien A, Havervall Sebastian, Adelmeijer Jelle, Lundström Annika, Rudberg Ann-Sofie, Magnusson Maria, Mackman Nigel, Thalin Charlotte, Lisman Ton
Surgical Research Laboratory Department of Surgery University of Groningen University Medical Center Groningen Groningen The Netherlands.
Division of Internal Medicine Department of Clinical Sciences Karolinska Institutet Danderyd Hospital Stockholm Sweden.
Res Pract Thromb Haemost. 2020 Dec 6;5(1):132-141. doi: 10.1002/rth2.12462. eCollection 2021 Jan.
Patients with severe coronavirus disease 2019 (COVID-19) are at significant risk of thrombotic complications. However, their prothrombotic state is incompletely understood. Therefore, we measured in vivo activation markers of hemostasis, plasma levels of hemostatic proteins, and functional assays of coagulation and fibrinolysis in plasma from patients with COVID-19 and determined their association with disease severity and 30-day mortality.
We included 102 patients with COVID-19 receiving various levels of respiratory support admitted to general wards, intermediate units, or intensive care units and collected plasma samples shortly after hospital admission.
Patients with COVID-19 with higher respiratory support had increased in vivo activation of coagulation and fibrinolysis, as reflected by higher plasma levels of d-dimer, thrombin-antithrombin, and plasmin-antiplasmin complexes as compared to patients with no to minimal respiratory support and healthy controls. Moreover, the patients with COVID-19 with higher respiratory support exhibited substantial ex vivo thrombin generation and lower ex vivo fibrinolytic capacity, despite higher doses of anticoagulant therapy compared to less severely ill patients. Fibrinogen, factor VIII, and von Willebrand factor levels increased, and ADAMTS13 levels decreased with increasing respiratory support in patients with COVID-19. Low platelet count; low levels of prothrombin, antithrombin, and ADAMTS13; and high levels of von Willebrand factor were associated with short-term mortality.
Severe COVID-19 is associated with prothrombotic changes with increased in vivo activation of coagulation and fibrinolysis, despite anticoagulant therapy.
2019年冠状病毒病（COVID-19）重症患者存在血栓形成并发症的重大风险。然而，他们的血栓前状态尚未完全明确。因此，我们检测了COVID-19患者血浆中止血的体内激活标志物、止血蛋白的血浆水平以及凝血和纤溶的功能测定，并确定了它们与疾病严重程度和30天死亡率的关联。
我们纳入了102例入住普通病房、中级病房或重症监护病房并接受不同水平呼吸支持的COVID-19患者，并在入院后不久采集血浆样本。
与未接受或仅接受极少呼吸支持的患者及健康对照相比，接受更高呼吸支持的COVID-19患者体内凝血和纤溶激活增加，表现为血浆d - 二聚体、凝血酶 - 抗凝血酶复合物和纤溶酶 - 抗纤溶酶复合物水平更高。此外，尽管与病情较轻的患者相比接受了更高剂量的抗凝治疗，但接受更高呼吸支持的COVID-19患者仍表现出大量体外凝血酶生成和较低的体外纤溶能力。随着COVID-19患者呼吸支持水平的增加，纤维蛋白原、凝血因子VIII和血管性血友病因子水平升高，而ADAMTS13水平降低。血小板计数低、凝血酶原、抗凝血酶和ADAMTS13水平低以及血管性血友病因子水平高与短期死亡率相关。
尽管进行了抗凝治疗，但重症COVID-19仍与血栓前变化相关，体内凝血和纤溶激活增加。
