恢复期血浆输注对重症和危重症新型冠状病毒肺炎患者中ADAMTS13-血管性血友病因子轴及内皮完整性的影响

Effects of convalescent plasma infusion on the ADAMTS13-von Willebrand factor axis and endothelial integrity in patients with severe and critical COVID-19.

作者信息

Zhang Quan, Ye Zhan, McGowan Paul, Jurief Christopher, Ly Andrew, Bignotti Antonia, Yada Noritaka, Zheng X Long

机构信息

Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, Kansas, USA.

Institute of Reproductive and Developmental Sciences, The University of Kansas Medical Center, Kansas City, Kansas, USA.

出版信息

Res Pract Thromb Haemost. 2023 Jan;7(1):100010. doi: 10.1016/j.rpth.2022.100010. Epub 2022 Dec 13.

DOI:10.1016/j.rpth.2022.100010

PMID:36531671

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9744678/

Abstract

BACKGROUND

Convalescent plasma infusion (CPI) was given to patients with COVID-19 during the early pandemic with mixed therapeutic efficacy. However, the impacts of CPI on the ADAMTS13-von Willebrand factor (VWF) axis and vascular endothelial functions are not known.

OBJECTIVES

To determine the impacts of CPI on the ADAMTS13-VWF axis and vascular endothelial functions.

METHODS

Sixty hospitalized patients with COVID-19 were enrolled in the study; 46 received CPI and 14 received no CPI. Plasma ADAMTS13 activity, VWF antigen, endothelial syndecan-1, and soluble thrombomodulin (sTM) were assessed before and 24 hours after treatment.

RESULTS

Patients with severe and critical COVID-19 exhibited significantly lower plasma ADAMTS13 activity than the healthy controls. Conversely, these patients showed a significantly increased VWF antigen. This resulted in markedly reduced ratios of ADAMTS13 to VWF in these patients. The levels of plasma ADAMTS13 activity in each patient remained relatively constant throughout hospitalization. Twenty-four hours following CPI, plasma ADAMTS13 activity increased by ∼12% from the baseline in all patients and ∼21% in those who survived. In contrast, plasma levels of VWF antigen varied significantly over time. Patients who died exhibited a significant reduction of plasma VWF antigen from the baseline 24 hours following CPI, whereas those who survived did not. Furthermore, patients with severe and critical COVID-19 showed significantly elevated plasma levels of syndecan-1 and sTM, similar to those found in patients with immune thrombotic thrombocytopenic purpura. Both syndecan-1 and sTM levels were significantly reduced 24 hours following CPI.

CONCLUSION

Our results demonstrate the relative deficiency of plasma ADAMTS13 activity and endothelial damage in patients with severe and critical COVID-19, which could be modestly improved following CPI therapy.

摘要

背景

在疫情早期，新冠病毒病（COVID-19）患者接受了恢复期血浆输注（CPI），但其治疗效果不一。然而，CPI对ADAMTS13-血管性血友病因子（VWF）轴及血管内皮功能的影响尚不清楚。

目的

确定CPI对ADAMTS13-VWF轴及血管内皮功能的影响。

方法

60例住院的COVID-19患者纳入本研究；46例接受CPI，14例未接受CPI。在治疗前及治疗后24小时评估血浆ADAMTS13活性、VWF抗原、内皮 Syndecan-1和可溶性血栓调节蛋白（sTM）。

结果

重型和危重型COVID-19患者的血浆ADAMTS13活性显著低于健康对照。相反，这些患者的VWF抗原显著升高。这导致这些患者中ADAMTS13与VWF的比值明显降低。每位患者的血浆ADAMTS13活性水平在整个住院期间保持相对稳定。CPI后24小时，所有患者的血浆ADAMTS13活性较基线升高约12%，存活患者升高约21%。相比之下，VWF抗原的血浆水平随时间变化显著。死亡患者在CPI后24小时血浆VWF抗原较基线显著降低，而存活患者则未出现这种情况。此外，重型和危重型COVID-19患者的血浆Syndecan-1和sTM水平显著升高，与免疫性血栓性血小板减少性紫癜患者相似。CPI后24小时，Syndecan-1和sTM水平均显著降低。