title: Reversibility of severe metabolic stress in stored platelets after in vitro plasma rescue or in vivo transfusion: restoration of secretory function and maintenance of platelet survival.
abstract: BACKGROUND
  Determining reversible aspects of the platelet storage lesion may result in improved function and survival of transfused platelets.
  
  
  METHODS
  Using a model of high-dose (apheresis-derived) platelet concentrates (PC), functional changes imposed by transient adverse metabolic conditions (pH < 6.0 for 1-2 hr) that could be reversed by autologous plasma rescue followed by standard platelet storage were investigated. Whole-blood-derived PCs were transfused into a small number of normal volunteers to determine platelet recovery and survival.
  
  
  RESULTS
  Without rescue, high-dose PCs developed severe in vitro functional derangements at the time of the pH nadir including 1) loss of resting morphology; 2) complete abrogation of osmotic recovery and platelet aggregation and glycoprotein IIb/IIIa up-regulation to agonist; and 3) decreased alpha-granule release. By contrast, spontaneous and agonist-induced binding of annexin V were unaffected by adverse metabolic conditions. Plasma rescue to an optimal pH improved morphology scores, stabilized osmotic recovery, and completely restored platelet secretory responses, as measured by aggregation, glycoprotein IIb/IIIa up-regulation, and alpha-granule release. In a limited number of studies, plasma rescue was accompanied by preserved in vivo platelet recovery and survival after autologous transfusion after 5 days of storage.
  
  
  CONCLUSIONS
  Transient derangement of platelet metabolism, which does not increase membrane phosphatidylserine exposure, causes in vitro functional abnormalities that are fully reversed or stabilized by metabolic rescue. Preliminary data suggest that such rescued platelets may have normal posttransfusion recovery and survival.
authors.affiliation: Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8035, USA. henry.rinder@yale.edu
authors.forename: Henry M
authors.initials: HM
authors.lastname: Rinder
authors.forename: Edward L
authors.initials: EL
authors.lastname: Snyder
authors.forename: Jayne B
authors.initials: JB
authors.lastname: Tracey
authors.forename: Dorothy
authors.initials: D
authors.lastname: Dincecco
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.forename: Laurence
authors.initials: L
authors.lastname: Baril
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rinder
authors.forename: Brian R
authors.initials: BR
authors.lastname: Smith
mesh_terms: D000138:Acidosis / Q000378:metabolism; D017304:Annexin A5 / Q000378:metabolism; D001781:Blood Component Removal; D001792:Blood Platelets / Q000378:metabolism*; D001793:Blood Preservation; D002470:Cell Survival; D006801:Humans; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D009997:Osmotic Pressure; D010085:Oxidative Phosphorylation; D019007:P-Selectin / Q000378:metabolism; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D017713:Platelet Transfusion
chemical_list: D017304:Annexin A5; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex