title: Small-molecule complement inhibitors cannot prevent the development of the platelet storage lesion.
abstract: BACKGROUND
  Suppression of the platelet (PLT) storage lesion would maintain PLT quality over longer storage times. An increased storage period would greatly improve the ability of blood agencies and hospitals to manage PLT inventories and minimize product wastage. Activation of the complement system has been proposed to play a role in initiating or potentiating the PLT storage lesion. This study examines the effect of complement inhibition on the development of the PLT storage lesion.
  
  
  METHODS
  Leukofiltered PLT concentrates (PCs) were split into miniunits containing the complement inhibitors N-acetylaspartylglutamic acid (NAAGA) or compstatin, a control peptide, or saline. Samples were collected up to Day 11 of storage. Complement activation was monitored as C3a generation. PLT quality was assessed by morphology, CD62 and CD63 expression, fibrinogen binding, pH, mean PLT volume, annexin V binding, and PLT viability. Caspase-3 activity served as a measure of PLT apoptosis.
  
  
  RESULTS
  At concentrations of NAAGA required to achieve approximately 50 percent complement inhibition, PLT activation, and caspase-3 activity were increased. Complement inhibition by compstatin was highly variable. Compstatin addition consistently resulted in a 37 to 55 percent inhibition of PLT caspase-3 activity, but PLT quality and viability were no different between compstatin PCs and control PCs over the storage time.
  
  
  CONCLUSIONS
  Neither NAAGA nor compstatin provided complete inhibition of complement over the storage period. Addition of these small-peptide inhibitors to PCs did not slow PLT storage lesion development, in spite of the partial inhibition of caspase-3 activity in the compstatin-treated PCs.
authors.affiliation: Department of Pathology and Laboratory Medicine, UBC, Vancouver, British Columbia, Canada.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Bradley
authors.forename: Brandi L
authors.initials: BL
authors.lastname: Read
authors.forename: Elena
authors.initials: E
authors.lastname: Levin
authors.forename: Dana V
authors.initials: DV
authors.lastname: Devine
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D001793:Blood Preservation / Q000379:methods*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004151:Dipeptides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010979:Platelet Function Tests
chemical_list: D004151:Dipeptides; D010456:Peptides, Cyclic; C111828:compstatin; C027172:isospaglumic acid; D053148:Caspase 3