title: Never-frozen liquid plasma blocks endothelial permeability as effectively as thawed fresh frozen plasma.
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.
  
  
  CONCLUSIONS
  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.
authors: From the Center for Translational Injury Research (CeTIR) (Y.C., A.D., M.M., Y.-W.W., C.E.W.,T.C.K., J.B.H.), Department of Surgery, University of Texas-Houston, Houston, Texas; and Blood Systems Research Institute (S.P.), Department of Laboratory Medicine and Surgery, University of California-San Francisco, San Francisco, California.
authors: Yanna
authors: Y
authors: Cao
authors: Anahita
authors: A
authors: Dua
authors: Nena
authors: N
authors: Matijevic
authors: Yao-Wei
authors: YW
authors: Wang
authors: Shibani
authors: S
authors: Pati
authors: Charles E
authors: CE
authors: Wade
authors: Tien C
authors: TC
authors: Ko
authors: John B
authors: JB
authors: Holcomb
mesh_terms: D001793:Blood Preservation; D002199:Capillary Permeability / Q000502:physiology*; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006487:Hemostasis; D006801:Humans; D008297:Male; D010949:Plasma / Q000502:physiology; D012151:Resuscitation / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha