title: Increased platelet storage time is associated with mitochondrial dysfunction and impaired platelet function.
abstract: BACKGROUND
  Hemorrhagic shock is a leading cause of death following severe trauma, and platelet transfusions are frequently necessary to achieve hemostasis. Platelets, however, require special storage conditions, and storage time has been associated with loss of platelet quality. We hypothesized that standard storage conditions have a deleterious effect on platelet mitochondrial function and platelet activation.
  
  
  METHODS
  Platelet donations were collected from healthy donors (n = 5) and stored in gas-permeable collection bags according to American Association of Blood Bank recommendations. Platelet units were sampled from day of collection (day 0) until day 7. High-resolution respirometry was used to assess baseline mitochondrial respiration, maximal oxygen utilization, and individual mitochondrial complex-dependent respiration. Fluorescence-activated cell sorting was performed to analyze mitochondrial content, mitochondrial reactive oxygen species, the expression of P-selectin (both before and after challenge with thrombin receptor-activating peptide), and apoptosis. Data were analyzed using analysis of variance and Pearson correlation (P < 0.05 significant).
  
  
  RESULTS
  Mitochondrial respiration decreased significantly in platelets stored longer than 2 d (P < 0.05). Platelets also demonstrated a persistent decrease in response to stimulation with thrombin receptor-activating peptide by the third day of storage (P < 0.05) as well as an increase in mitochondrial reactive oxygen species and apoptosis (P < 0.05). Mitochondrial respiration significantly correlated with platelet capacity to activate (r = 0.8, P < 0.05).
  
  
  CONCLUSIONS
  Platelet mitochondrial respiratory function and activation response decrease significantly in platelets stored for 3 d or more. Because platelet transfusions almost universally occur between the third and fifth day of storage, our findings may have significant clinical importance and warrant further in vivo analysis.
authors.affiliation: Division of Traumatology, Department of Surgery, Critical Care and Acute Care Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: José Paul
authors.initials: JP
authors.lastname: Perales Villarroel
authors.forename: Ronald
authors.initials: R
authors.lastname: Figueredo
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Guan
authors.forename: Maurizio
authors.initials: M
authors.lastname: Tomaiuolo
authors.forename: Mehmet A
authors.initials: MA
authors.lastname: Karamercan
authors.forename: John
authors.initials: J
authors.lastname: Welsh
authors.forename: Mary A
authors.initials: MA
authors.lastname: Selak
authors.forename: Lance B
authors.initials: LB
authors.lastname: Becker
authors.forename: Carrie
authors.initials: C
authors.lastname: Sims
mesh_terms: D017209:Apoptosis; D001792:Blood Platelets / Q000166:cytology* / Q000378:metabolism*; D001793:Blood Preservation; D019069:Cell Respiration; D006487:Hemostasis; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000378:metabolism; D015539:Platelet Activation; D017713:Platelet Transfusion; D017382:Reactive Oxygen Species / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000097:blood / Q000628:therapy*; D013997:Time Factors; D014947:Wounds and Injuries / Q000097:blood / Q000628:therapy
chemical_list: D017382:Reactive Oxygen Species
keywords: High-resolution respirometry; Mitochondrial respiratory capacity; Platelet activation; Resuscitation; Systemic organ