title: Protective effects of fresh frozen plasma on vascular endothelial permeability, coagulation, and resuscitation after hemorrhagic shock are time dependent and diminish between days 0 and 5 after thaw.
abstract: BACKGROUND
  Clinical studies have shown that resuscitation with fresh frozen plasma (FFP) is associated with improved outcome after severe hemorrhagic shock (HS). We hypothesized that in addition to its effects on hemostasis, FFP has protective and stabilizing effects on the endothelium that translate into diminished endothelial cell (EC) permeability and improved resuscitation in vivo after HS. We further hypothesized that the beneficial effects of FFP would diminish over 5 days of routine storage at 4 degrees C.
  
  
  METHODS
  EC permeability was induced by hypoxia and assessed by the passage of 70-kDa Dextran between monolayers. Thrombin generation time and coagulation factor levels or activity were assessed in FFP. An in vivo rat model of HS and resuscitation was used to determine the effects of FFP on hemodynamic stability.
  
  
  RESULTS
  Thawed FFP inhibits EC permeability in vitro by 10.2-fold. Protective effects diminish (to 2.5-fold) by day 5. Thrombin generation time is increased in plasma that has been stored between days 0 and 5. In vivo data show that day 0 FFP is superior to day 5 FFP in maintaining mean arterial pressure in rats undergoing HS with resuscitation.
  
  
  CONCLUSIONS
  Both in vitro and in vivo studies show that FFP has beneficial effects on endothelial permeability, vascular stability, and resuscitation in rats after HS. The benefits are independent of hemostasis and diminish between days 0 and 5 of storage.
authors.affiliation: Department of Surgery and Center for Translational Injury Research, University of Texas Health Science Center, Houston, Texas 77030, USA. Shibani.Pati@uth.tmc.edu
authors.forename: Shibani
authors.initials: S
authors.lastname: Pati
authors.forename: Nena
authors.initials: N
authors.lastname: Matijevic
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Doursout
authors.forename: Tien
authors.initials: T
authors.lastname: Ko
authors.forename: Yanna
authors.initials: Y
authors.lastname: Cao
authors.forename: Xiyun
authors.initials: X
authors.lastname: Deng
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Kozar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hartwell
authors.forename: Jodie
authors.initials: J
authors.lastname: Conyers
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology*; D002199:Capillary Permeability / Q000502:physiology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D004730:Endothelium, Vascular / Q000378:metabolism*; D005500:Follow-Up Studies; D006801:Humans; D010949:Plasma; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors