Elevated tissue factor pathway inhibitor delays thrombin generation in COVID-19 but is not associated with clinical outcomes

Alicia S. Eustes; Meena Kumari Palani Kumar; Julie A. Peterson; Alan E. Mast; Steven R. Lentz; Sanjana Dayal

doi:10.1016/j.bvth.2025.100071

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Elevated tissue factor pathway inhibitor delays thrombin generation in COVID-19 but is not associated with clinical outcomes

Journal article

Open access

Peer reviewed

Elevated tissue factor pathway inhibitor delays thrombin generation in COVID-19 but is not associated with clinical outcomes

Alicia S. Eustes, Meena Kumari Palani Kumar, Julie A. Peterson, Alan E. Mast, Steven R. Lentz and Sanjana Dayal

Blood Vessels, Thrombosis & Hemostasis, Vol.2(3), 100071

08/2025

DOI: 10.1016/j.bvth.2025.100071

PMCID: PMC12320461

PMID: 40765912

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Abstract

•Elevation of endogenous tissue factor pathway inhibitor delays the initiation of thrombin generation in hospitalized patients with COVID-19.•Plasma TFPI not associated with thrombosis or 30-day mortality. Plasma levels of tissue factor pathway inhibitor (TFPI) are elevated in many patients with COVID-19 but the role of TFPI in COVID-19 coagulopathy remains elusive. We sought to determine the contribution of TFPI to thrombin generation in patients with COVID-19 and assess its association with thrombosis and other clinical outcomes. We utilized blood samples from an early COVID-19 clinical trial of adult patients hospitalized with acute COVID-19 from April 2020 to January 2021 (NCT04360824). Plasma TFPI was measured by ELISA and thrombin generation potential was measured in the presence or absence of TFPI neutralizing antibodies. Thromboelastography was performed with whole blood samples. We found that plasma TFPI was elevated in COVID-19 patients compared to healthy subjects. Thrombin generation triggered by exogenous TF and phospholipids was increased in COVID-19, reflected by greater peak thrombin, velocity index, and endogenous thrombin potential; however, the time to initiation of thrombin generation (lag time) was delayed. Addition of a neutralizing anti-TFPI antibody significantly shortened the lag time in COVID-19 and normalized the difference in lag time between COVID-19 and healthy subjects. Plasma TFPI was positively associated with lag time, time to peak thrombin, and time to initial clot formation in thromboelastography. Multivariate analysis demonstrated that TFPI correlated with lag time and time to reach peak thrombin but not with 30-day mortality, thrombosis, or other adverse clinical outcomes. We conclude that elevated plasma TFPI delays the initiation of thrombin generation and clot formation but is not associated with thrombosis in patients hospitalized with COVID-19.

COVID-19

thrombin generation

Tissue factor pathway inhibitor (TFPI)

Details

Title: Subtitle: Elevated tissue factor pathway inhibitor delays thrombin generation in COVID-19 but is not associated with clinical outcomes
Creators: Alicia S. Eustes - University of Iowa
Meena Kumari Palani Kumar - University of Iowa
Julie A. Peterson - Versiti Blood Center of Wisconsin
Alan E. Mast - Versiti Blood Center of Wisconsin
Steven R. Lentz - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Sanjana Dayal - University of Iowa
Resource Type: Journal article
Publication Details: Blood Vessels, Thrombosis & Hemostasis, Vol.2(3), 100071
DOI: 10.1016/j.bvth.2025.100071
PMID: 40765912
PMCID: PMC12320461
NLM abbreviation: Blood Vessel Thromb Hemost
ISSN: 2950-3272
eISSN: 2950-3272
Publisher: Elsevier Inc
Language: English
Electronic publication date: 04/2025
Date published: 08/2025
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984821353002771

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