Pro-coagulant lipids in physiological ratios found in the activated platelet membrane do not impact clot structure or fibrinolysis in purified assays
File(s)
Author(s)
Type
Journal Article
Abstract
Purpose: A central role for the pro-coagulant membrane comprising aminophospholipids (aPL) and enzymatically oxidized phospholipids (eoxPL) in promoting hemostasis via interaction with coagulation factor Gla domains is well established. However, little is known about their interactions with the fibrinolytic pathway, their ability to alter clot structure or to support the activated protein C (APC) pathway. Previous studies used membrane liposome compositions that differ from those expected physiologically and/or generated inconsistent findings. To address this, pro-coagulant membranes comprising physiological proportions of aPL and eoxPL will be tested for their ability to support fibrinolysis using standard assays.
Methods: The impact of phospholipids on clot structure and clot lysis was tested using absorbance-based assays. To investigate the impact of PS or eoxPL on fibrinolysis, plasmin was monitored chromogenically, and clot dissolution measured in a purified lysis system activated by tissue plasminogen activator or urokinase. To determine the impact of eoxPL on APC/protein S, FVa was incubated with APC (± protein S) in a purified prothrombinase assay.
Results: At the concentrations of lipids tested in our study, PS did not significantly impact clot structure or fibrinolysis. Similarly, eoxPL did not impact either fibrinolysis or activity of APC/Protein S.
Conclusion: Using liposome compositions that approximate activated blood cells, we found that the pro-coagulant membrane is unlikely to influence either clot structure or fibrinolytic activity directly, beyond its well characterized role in supporting Gla dependent coagulation factors and the actions of platelet associated proteins/receptors.
Methods: The impact of phospholipids on clot structure and clot lysis was tested using absorbance-based assays. To investigate the impact of PS or eoxPL on fibrinolysis, plasmin was monitored chromogenically, and clot dissolution measured in a purified lysis system activated by tissue plasminogen activator or urokinase. To determine the impact of eoxPL on APC/protein S, FVa was incubated with APC (± protein S) in a purified prothrombinase assay.
Results: At the concentrations of lipids tested in our study, PS did not significantly impact clot structure or fibrinolysis. Similarly, eoxPL did not impact either fibrinolysis or activity of APC/Protein S.
Conclusion: Using liposome compositions that approximate activated blood cells, we found that the pro-coagulant membrane is unlikely to influence either clot structure or fibrinolytic activity directly, beyond its well characterized role in supporting Gla dependent coagulation factors and the actions of platelet associated proteins/receptors.
Date Issued
2025-11-08
Date Acceptance
2025-09-25
Citation
Journal of Blood Medicine, 2025, 16, pp.509-521
ISSN
1179-2736
Publisher
Dove Medical Press
Start Page
509
End Page
521
Journal / Book Title
Journal of Blood Medicine
Volume
16
Copyright Statement
© 2025 Morgan et al. This work is published by Dove Medical Press Limited, and licensed under a Creative Commons Attribution License. The full terms of the License are available at https://creativecommons.org/licenses/by/4.0/. The license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41235326
PII: 527558
Subjects
activated protein C
fibrin
phosphatidylserine
phospholipids
plasmin
protein S
Publication Status
Published
Coverage Spatial
New Zealand
Date Publish Online
2025-11-08