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Thromb Haemost 2022; 122(03): 344-352
DOI: 10.1055/a-1508-8347
Coagulation and Fibrinolysis

Plasma Levels of Big Endothelin-1 Are Associated with Renal Insufficiency and In-Hospital Mortality of Immune Thrombotic Thrombocytopenic Purpura

Ruinan Lu
1   Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States
2   Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China
,
X. Long Zheng 
1   Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States
› Institutsangaben Funding This study was supported in part by grants from National Heart, Lung, and Blood Institute (HL126724 to X.L.Z.) and a State Scholarship Fund from China Scholarship Council (2019-0832-0234 to R.L.).
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Abstract

Immune thrombotic thrombocytopenic purpura (iTTP) is caused by severe deficiency of plasma ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity. Despite advances in early diagnosis and management, the mortality rate of acute iTTP remains high in a large part of world where access to some of the most novel therapies is limited. To determine the role of plasma big endothelin-1 (bigET-1) or its bioactive product ET-1 as a biomarker and/or a pathogenic factor in acute iTTP, plasma levels of bigET-1 were determined using an immunoassay in patients with iTTP on admission and during remission, as well as in healthy controls; moreover, the biological effect of ET-1 in thrombus formation was determined by a microfluidic assay. We show that plasma levels of bigET-1 were dramatically increased in patients with acute iTTP on admission, which was significantly decreased during clinical response/remission; elevated admission levels of plasma bigET-1 were associated with low estimated glomerular filtration rate, the need for intensive care unit admission or intubation, and in-hospital mortality. Moreover, an addition of a bioactive product ET-1 to cultured endothelial cells in a microfluidic channel significantly accelerated the rate of thrombus formation under arterial flow. Our results demonstrate for the first time a potential role of measuring plasma bigET-1 in patients with acute iTTP in assessing the disease severity and risk of in-hospital mortality, which may help stratify patients for a more aggressive monitoring and therapeutic strategy; also, the bioactive ET-1, derived from bigET-1, may result in acute renal injury in TTP patient, likely through its vasoconstriction and prothrombotic properties.

Keywords

endothelial ET-1 - TTP - renal injury - mortality - outcome

Author Contributions

R.L., and X.L.Z. both designed the research, performed the experiments, and analyzed the results, as well as wrote the manuscript.


Supplementary Material



Publikationsverlauf

Eingereicht: 23. Februar 2021

Angenommen: 12. Mai 2021

Accepted Manuscript online:
13. Mai 2021

Artikel online veröffentlicht:
21. Juni 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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