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Platelet storage lesion underlies changes in plasminogen activator inhibitor-1 activity in stored whole blood
Elizabeth R Maginot1, Nicolle K Barmettler, Flobater I Gawargi
1Department of Surgery, Division of Acute Care Surgery, University of Nebraska Medical Center, Omaha, NE (E.R.M., N.K.B., F.I.G., C.M.W., D.C.H., A.A.C., K.S.S., T.B.M., G.E.V., R.H., C.D.B.); Department of Surgery, Ernest E Moore Shock Trauma Center at Denver Health, Denver, CO (E.E.M.); Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO (E.E.M.); Department of Surgery, AdventHealth Porter, Denver, CO (H.B.M.); Department of Pathology, University of Nebraska Medical Center, Omaha, NE (N.G., A.B.); Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE (C.D.B.).
Background:
Whole blood transfusion is increasingly used in trauma resuscitation. However, stored whole blood units demonstrate increasing susceptibility to tissue plasminogen activator-mediated fibrinolysis despite paradoxical increases seen in plasminogen activator inhibitor-1 (PAI-1) activity over time. Whether early variability in PAI-1activity exists across whole blood units and the biologic contributors to this variability remain unclear. Two distinct donor pools were identified: one with high PAI-1 activity and one with low PAI-1 activity. We set out to determine whether PAI-1 activity in whole blood donors primarily comes from the endothelium or from platelet degranulation.
Methods:
Plasma from whole blood units (n = 28) was generated via serial centrifugation at two time points during storage (Days 1-3 and Day 21). Activity assays were performed for PAI-1 using a modified enzyme-linked immunosorbent assays that only captures active PAI-1. Soluble CD40 ligand (sCD40L), a platelet-derived marker of activation, degranulation and death, and total von Willebrand Factor antigen levels, which are highly specific for endothelial degranulation, were quantified using enzyme-linked immunosorbent assays. Statistical analysis was performed via two-tailed t-tests. Significance was set at p <0.05.
Results:
Whole blood units stratified into distinct high and low PAI-1 activity cohorts at early storage time points. Over storage, PAI-1 activity increased overall. sCD40L levels increased approximately 4-fold during storage, consistent with a platelet storage lesion. At early time points, both sCD40L and von Willebrand Factor antigen levels were significantly higher in the high PAI-1 cohort, suggesting contributions from both platelet-derived and donor endothelial factors.
Conclusion:
Stored whole blood demonstrates early, donor-dependent heterogeneity in antifibrinolytic potential, reflected by distinct PAI-1 activity cohorts at time of donation. This appears to have a mixed source, with evidence for both endothelial and platelet factors that may differ from donor to donor. (J Trauma Acute Care Surg. 2026;000: 000-000. Copyright © 2026 Wolters Kluwer Health, Inc. All rights reserved.).
Study Type:
Basic science.
Level Of Evidence:
Basic Science, Level V.
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