Abstract

Background: Patients with COVID-19 have a higher risk of thrombosis and thromboembolism, but the underlying mechanism(s) remain to be fully elucidated. In patients with COVID-19, high lipoprotein(a) (Lp(a)) is positively associated with the risk of ischemic heart disease. Lp(a), composed of an apoB-containing particle and apolipoprotein(a) (apo(a)), inhibits the key fibrinolytic enzyme, tissue-type plasminogen activator (tPA). However, whether the higher Lp(a) associates with lower tPA activity, the longitudinal changes of these parameters in hospitalized patients with COVID-19, and their correlation with clinical outcomes are unknown.

Objectives: To assess if Lp(a) associates with lower tPA activity in COVID-19 patients, and how in COVID-19 populations Lp(a) and tPA change post infection.

Methods: Endogenous tPA enzymatic activity, tPA or Lp(a) concentration were measured in plasma from hospitalized patients with and without COVID-19. The association between plasma tPA and adverse clinical outcomes was assessed.

Results: In hospitalized patients with COVID-19, we found lower tPA enzymatic activity and higher plasma Lp(a) than that in non–COVID-19 controls. During hospitalization, Lp(a) increased and tPA activity decreased, which associates with mortality. Among those who survived, Lp(a) decreased and tPA enzymatic activity increased during recovery. In patients with COVID-19, tPA activity is inversely correlated with tPA concentrations, thus, in another larger COVID-19 cohort, we utilized plasma tPA concentration as a surrogate to inversely reflect tPA activity. The tPA concentration was positively associated with death, disease severity, plasma inflammatory, and prothrombotic markers, and with length of hospitalization among those who were discharged.

Conclusion: High Lp(a) concentration provides a possible explanation for low endogenous tPA enzymatic activity, and poor clinical outcomes in patients with COVID-19.

Document Type

Article

Publication Date

8-2023

Notes/Citation Information

© 2023 The Author(s). Published by Elsevier Inc. on behalf of International Society on Thrombosis and Haemostasis. This is an open access article under the CC BY- NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.rpth.2023.102164

Funding Information

This study was funded by a COVID-19 Rapid Response Grant from the Cullen RunFoundation through the MCW Cardiovascular Center (to ZZ), a startup fund from the MCW and Versiti BRI (to ZZ), a Fellow Scholar Award and a Supplement Award from the American Society of Hematology (to ZZ and TJB), a Career Development Award from the American Heart Association (to ZZ, 19CDA34660043 and TJB 18CDA34110203AHA), R01HL163516 (to ZZ), R01HL167917 (to TJB), 20PRE35210461 (to WZ), NIH AI159536 (to WC), HL148120 (to RW), HL161127 (to RW), and R35HL144993 (to JSB). This research was, in part, funded by the National Institutes of Health (NIH) Agreement 1OT2HL156812 through the National Heart, Lung, and Blood Institute (NHLBI) CONNECTS program. The views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of the NIH. The MCW Clinical Research Data Warehouse was supported by the NIH National Center for Advancing Translational Sciences (to Clinical & Translational Science Institute of Southeast Wisconsin, UL1TR001436). The CAP accredited MCW Tissue Bank COVID-19 Program was supported by the MCW department of Pathology, the MCW department of Medicine.

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