PDF(Pubmed)
Abstract：
The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the coagulation system is not fully understood. SARS-CoV-2 penetrates cells through angiotensin-converting enzyme 2 (ACE2) receptors, leading to its downregulation. Des-arginine9-bradykinin (DA9B) is degraded by ACE2 and causes vasodilation and increased vascular permeability. Furthermore, DA9B is associated with impaired platelet function. Therefore, the aim of this study was to evaluate the effects of DA9B on platelet function and coagulopathy in critically ill coronavirus disease 2019 (COVID-19) patients. In total, 29 polymerase-positive SARS-CoV-2 patients admitted to the intensive care unit of the University Hospital of Giessen and 29 healthy controls were included. Blood samples were taken, and platelet impedance aggregometry and rotational thromboelastometry were performed. Enzyme-linked immunosorbent assays measured the concentrations of DA9B, bradykinin, and angiotensin 2. Significantly increased concentrations of DA9B and angiotensin 2 were found in the COVID-19 patients. A negative effect of DA9B on platelet function and intrinsic coagulation was also found. A sub-analysis of moderate and severe acute respiratory distress syndrome patients revealed a negative association between DA9B and platelet counts and fibrinogen levels. DA9B provokes inhibitory effects on the intrinsic coagulation system in COVID-19 patients. This negative feedback seems reasonable as bradykinin, which is transformed to DA9B, is released after contact activation. Nevertheless, further studies are needed to confirm our findings.
摘要：
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）对凝血系统的影响尚未完全了解。SARS-CoV-2通过血管紧张素转换酶2（ACE2）受体穿透细胞，导致其下调。Des-精氨酸9-缓激肽（DA9B）被ACE2降解，并导致血管舒张和血管通透性增加。此外，DA9B与受损的血小板功能相关。因此,本研究的目的是评估DA9B对重症冠状病毒病2019(COVID-19)患者血小板功能和凝血功能障碍的影响.总的来说,纳入了吉森大学医院重症监护病房的29名聚合酶阳性SARS-CoV-2患者和29名健康对照。采集了血样,并进行了血小板阻抗聚集测定法和旋转血栓弹性测定法.酶联免疫吸附试验测量DA9B的浓度，缓激肽,和血管紧张素2.在COVID-19患者中发现DA9B和血管紧张素2的浓度显着增加。还发现DA9B对血小板功能和固有凝血的负面影响。对中度和重度急性呼吸窘迫综合征患者的亚分析显示，DA9B与血小板计数和纤维蛋白原水平之间呈负相关。DA9B对COVID-19患者固有凝血系统具有抑制作用。这种负面反馈似乎是合理的，就像缓激肽一样，转换为DA9B，触点激活后释放。然而，我们需要进一步的研究来证实我们的发现.
