Generation of kinins during preparation and storage of whole blood-derived platelet concentrates.
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.
Moreau
Marie Eve
ME
Faculty of Pharmacy, Faculty of Arts and Sciences, Department of Mathematics and Statistics, University of Montreal, Montreal, Quebec, Canada.
Thibault
Louis
L
Désormeaux
Anik
A
Chagnon
Miguel
M
Lemieux
Réal
R
Robillard
Pierre
P
Marceau
François
F
Colman
Robert W
RW
Lepage
Yves
Y
Rivard
Georges-Etienne
GE
Adam
Albert
A
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
D007705:Kinins; D007703:Peptidyl-Dipeptidase A