Platelet storage lesion underlies changes in plasminogen activator inhibitor-1 activity in stored whole blood.

Abstract

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. 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. 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. 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.). Basic science. Basic Science, Level V.