Acetaldehyde exposure alters fibrin polymerization, fibrinolysis, and fibrin network structure in vitro

Background: Fibrin(ogen), the primary structural component of blood clots, plays a critical role in thrombosis and hemostasis. Posttranslational modifications to fibrinogen that occur upon exposure to reactive endogenous metabolites or xenobiotics during inflammation and disease alter polymer format...

Full description

Saved in:
Bibliographic Details
Main Authors: Shakthi Rave, Daniel P. Hu, Rebecca A. Risman, Warishah Khan, Valerie Tutwiler, Lauren G. Poole
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Research and Practice in Thrombosis and Haemostasis
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2475037925002456
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background: Fibrin(ogen), the primary structural component of blood clots, plays a critical role in thrombosis and hemostasis. Posttranslational modifications to fibrinogen that occur upon exposure to reactive endogenous metabolites or xenobiotics during inflammation and disease alter polymer formation, network structure, or susceptibility to lysis. Acetaldehyde is a reactive byproduct of hepatic ethanol metabolism and ubiquitous environmental pollutant that forms stable adducts with macromolecules. Previous studies report that acetaldehyde impairs the function of multiple coagulation factors, including fibrinogen. Objectives: The study aimed to test the hypothesis that exposure of fibrinogen to acetaldehyde alters fibrin polymerization, clot structure, and fibrinolysis. Methods: Fibrinogen was incubated with 0, 90, 180, or 270 mM acetaldehyde for 30 minutes and then dialyzed to remove excess acetaldehyde. Fibrin polymerization, clot structure, and fibrinolysis were assessed. Results: Analysis of turbidity curves indicated that exposure to 180 and 270 mM acetaldehyde significantly decreased the rate of thrombin-driven fibrin formation and the maximum absorbance compared to control. Turbidimetric analysis and scanning electron microscopy of fully formed clots revealed that acetaldehyde exposure (180 and 270 mM) caused formation of more densely packed fibrin networks of thin fibers. Finally, acetaldehyde exposure tended to accelerate the external lysis of fully formed clots by plasmin. In contrast, acetaldehyde significantly delayed internal clot lysis when fibrinogen was incubated with tissue plasminogen activator and plasminogen before clot formation. Conclusions: These results indicate that acetaldehyde exposure drives the formation of prothrombotic fibrin clots that are resistant to lysis, suggesting that endogenous or exogenous acetaldehyde exposure may influence thrombosis risk.
ISSN:2475-0379