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

Blood Vessels, Thrombosis & Hemostasis Pub Date : 2025-04-29 DOI:10.1016/j.bvth.2025.100071

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

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Abstract

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 used blood samples from an early COVID-19 clinical trial of adult patients hospitalized with acute COVID-19 from April 2020 to January 2021 (ClinicalTrials.gov identifier: NCT04360824). Plasma TFPI was measured by enzyme-linked immunosorbent assay, 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 patients with COVID-19 compared with healthy individuals. 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 those with COVID-19 and healthy individuals. 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.

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组织因子通路抑制剂升高可延缓COVID-19患者凝血酶的产生，但与临床结果无关

摘要许多新冠肺炎患者血浆组织因子通路抑制剂（TFPI）水平升高，但TFPI在新冠肺炎凝血功能中的作用尚不明确。我们试图确定TFPI对COVID-19患者凝血酶生成的贡献，并评估其与血栓形成和其他临床结果的关联。我们使用了2020年4月至2021年1月住院的急性COVID-19成年患者的早期COVID-19临床试验的血液样本（ClinicalTrials.gov识别码：NCT04360824）。采用酶联免疫吸附法测定血浆TFPI，在存在或不存在TFPI中和抗体的情况下测定凝血酶生成电位。用全血样本进行血栓弹性成像。我们发现，与健康个体相比，COVID-19患者血浆TFPI升高。外源性TF和磷脂触发的凝血酶生成在COVID-19中增加，表现为凝血酶峰值、速度指数和内源性凝血酶电位的增加；然而，开始凝血酶产生的时间（滞后时间）被推迟。加入一种中和性抗tfpi抗体可显著缩短COVID-19的滞后时间，使COVID-19感染者与健康人群的滞后时间差异正常化。血浆TFPI与血栓弹性成像的滞后时间、凝血酶峰值时间和初始凝块形成时间呈正相关。多变量分析表明，TFPI与延迟时间和达到凝血酶峰值的时间相关，但与30天死亡率、血栓形成或其他不良临床结果无关。我们得出结论，血浆TFPI升高延缓了COVID-19住院患者凝血酶生成和凝块形成的启动，但与血栓形成无关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Blood Vessels, Thrombosis & Hemostasis

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