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

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

doi:10.1016/j.rpth.2022.100010

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

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

Authors

Quan Zhang¹, Zhan Ye¹, Paul McGowan¹, Christopher Jurief¹, Andrew Ly¹, Antonia Bignotti¹, Noritaka Yada¹, X Long Zheng^{1

2}

Affiliations

¹ Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas City, Kansas, USA.
² Institute of Reproductive and Developmental Sciences, The University of Kansas Medical Center, Kansas City, Kansas, USA.

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.

Keywords: ADAMTS13; ADAMTS13, A Disintegrin And Metalloprotease with ThromboSpondin Type 1 Repeats, 13; COVID-19; COVID-19, Coronavirus disease 2019; CPI, Convalescent plasma infusion; IQR, Interquartile range; TPE, Therapeutic plasma exchange; VWF; VWF, von Willebrand factor; convalescent plasma; endothelial injury; iTTP, Immune thrombotic thrombocytopenic purpura; sTM, Soluble thrombomodulin; sydecan-1; thrombomodulin.

Abstract

Grants and funding