Generation of kinins during preparation and storage of whole blood–derived platelet concentrates

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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. STUDY DESIGN AND METHODS: The concentration of BK and one of its vasoactive metabolites, des‐arginine9‐BK (des‐Arg9‐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. CONCLUSION: 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.
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