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
1   Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States
› Author Affiliations
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.).


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.

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

Publication History

Received: 23 February 2021

Accepted: 12 May 2021

Publication Date:
13 May 2021 (online)

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