Whole blood becomes increasingly susceptible to tPA-mediated fibrinolysis with storage.

Abstract

Whole blood transfusion is increasingly used in trauma resuscitation, but its hemostatic effectiveness over time remains unclear. Separately, hyperfibrinolysis is a known pathologic result of major trauma that contributes to death by exsanguination. Emerging data suggest the functional integrity of whole blood components, particularly fibrinogen, may deteriorate during WB storage, but no studies on how whole blood storage impacts sensitivity to tPA have been performed to date. This study set out to investigate how whole blood storage affects susceptibility to tissue plasminogen activator (tPA)-mediated fibrinolysis and explore potential mechanisms contributing to any observed changes. Whole blood was obtained (n = 34) from a local urban blood bank and stored at 4C. Thromboelastography with 75 ng/mL tPA was performed at three storage intervals: Days 1-3, Days 7-11, and Day 21. Fibrinogen function was evaluated using alpha angle and platelet function via maximum amplitude metrics. Plasminogen activator inhibitor type 1 activity was quantified in plasma from stored whole blood via a commercially available activity assay, and hemolysis was measured using Harboe method. ANOVA and Spearman correlations were performed with significance set at p < 0.05. Sensitivity to tPA-induced fibrinolysis increased significantly with storage duration, with LY30 values rising nearly threefold by expiration ( p < 0.0001). Alpha angle and MA declined over time, and MA had a strong inverse correlation with tPA sensitivity. Hemolysis rose with storage ( p < 0.0001) but was not significantly correlated with tPA sensitivity ( r = 0.231, p < 0.073). Plasminogen activator inhibitor type 1 levels paradoxically increased with time, suggesting it does not drive the observed increase in tPA sensitivity. Stored whole blood becomes increasingly vulnerable to tPA-mediated fibrinolysis, potentially due to a combination of declining fibrinogen and platelet function. These findings raise considerations for clinical use of older whole blood units and support the potential role of adjunctive therapies during trauma resuscitation.