Never-frozen liquid plasma blocks endothelial permeability as effectively as thawed fresh frozen plasma

J Trauma Acute Care Surg. 2014 Jul;77(1):28-33; discussion 33. doi: 10.1097/TA.0000000000000276.

Abstract

Background: Thawed fresh frozen plasma (TP) is a preferred plasma product for resuscitation but can only be used for up to 5 days after thawing. Never-frozen, liquid plasma (LQP) is approved for up to 26 days when stored at 1°C to 6°C. We have previously shown that TP repairs tumor necrosis factor α (TNF-α)-induced permeability in human endothelial cells (ECs). We hypothesized that stored LQP repairs permeability as effectively as TP.

Methods: Three single-donor LQP units were pooled. Aliquots were frozen, and samples were thawed on Day 0 (TP0) then refrigerated for 5 days (TP5). The remaining LQP was kept refrigerated for 28 days, and aliquots were analyzed every 7 days. The EC monolayer was stimulated with TNF-α (10 ng/mL), inducing permeability, followed by a treatment with TP0, TP5, or LQP aged 0, 7, 14, 21, and 28 days. Permeability was measured by leakage of fluorescein isothiocyanate-dextran through the EC monolayer. Hemostatic profiles of samples were evaluated by thrombogram and thromboelastogram. Statistical analysis was performed using two-way analysis of variance, with p < 0.05 deemed significant.

Results: TNF-α increased permeability of the EC monolayer twofold compared with medium control. There was a significant decrease in permeability at 0, 7, 14, 21, and 28 days when LQP was used to treat TNF-α-induced EC monolayers (p < 0.001). LQP was as effective as TP0 and TP5 at reducing permeability. Stored LQP retained the capacity to generate thrombin and form a clot.

Conclusion: LQP corrected TNF-α-induced EC permeability and preserved hemostatic potential after 28 days of storage, similar to TP stored for 5 days. The significant logistical benefit (fivefold) of prolonged LQP storage improves the immediate availability of plasma as a primary resuscitative fluid for bleeding patients.

MeSH terms

  • Blood Preservation*
  • Capillary Permeability / physiology*
  • Endothelial Cells / physiology*
  • Endothelium, Vascular / physiology
  • Female
  • Hemostasis
  • Humans
  • Male
  • Plasma* / physiology
  • Resuscitation / methods
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Tumor Necrosis Factor-alpha