title: Generation of kinins during preparation and storage of whole blood-derived platelet concentrates.
abstract: BACKGROUND
  Leukoreduction of platelet (PLT) concentrates (PCs) may be associated with hypotension in recipients, and a role for bradykinin (BK)-related peptides has been proposed for this side effect.
  
  
  METHODS
  The concentration of BK and one of its vasoactive metabolites, des-arginine(9)-BK (des-Arg(9)-BK), was measured in a large number of PCs as a function of leukoreduction and storage duration with specific enzyme immunoassays and complementary techniques.
  
  
  RESULTS
  On Day 0 of storage, kinins were detected in leukoreduced and unfiltered PCs at a concentration lower than 100 pg per mL. During storage, both kinin levels peaked on Day 5 of storage, with a concentration higher than 1 ng per mL in 22 percent of PCs whether filtered on Day 0 or not. Physicochemical and pharmacologic characterizations of immunoreactive kinins confirm their nature. In vitro activation of the contact system of the corresponding PLT-poor plasma showed that a high kinin concentration on Day 5 of the storage corresponded with a low kinin-forming capacity of plasma. On Day 7, BK was no longer elevated presumably due to its degradation and the depletion of kinin-forming capacity of the plasma in stored PCs. The activities of metallopeptidases that metabolize BK-related peptides in plasma from PCs were at levels similar to those recorded in the plasma of a normal reference population and were unaffected by storage.
  
  
  CONCLUSIONS
  Storage of PCs contributes to the hydrolysis of high-molecular-weight kininogen and generation of pharmacologically relevant BK levels that might pose a hazard in susceptible patients.
authors.affiliation: Faculty of Pharmacy, Faculty of Arts and Sciences, Department of Mathematics and Statistics, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Marie Eve
authors.initials: ME
authors.lastname: Moreau
authors.forename: Louis
authors.initials: L
authors.lastname: Thibault
authors.forename: Anik
authors.initials: A
authors.lastname: Désormeaux
authors.forename: Miguel
authors.initials: M
authors.lastname: Chagnon
authors.forename: Réal
authors.initials: R
authors.lastname: Lemieux
authors.forename: Pierre
authors.initials: P
authors.lastname: Robillard
authors.forename: François
authors.initials: F
authors.lastname: Marceau
authors.forename: Robert W
authors.initials: RW
authors.lastname: Colman
authors.forename: Yves
authors.initials: Y
authors.lastname: Lepage
authors.forename: Georges-Etienne
authors.initials: GE
authors.lastname: Rivard
authors.forename: Albert
authors.initials: A
authors.lastname: Adam
mesh_terms: D000368:Aged; D000465:Algorithms; D001792:Blood Platelets; D001793:Blood Preservation; D001800:Blood Specimen Collection / Q000379:methods*; D002478:Cells, Cultured; D005260:Female; D006440:Hemofiltration / Q000379:methods*; D006801:Humans; D007118:Immunoassay; D007705:Kinins / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism
chemical_list: D007705:Kinins; D007703:Peptidyl-Dipeptidase A