Generation of Kinins during Preparation and Storage of Leukoreduced Platelet Concentrates.

BACKGROUND. Severe hypotensive reactions can occur following transfusion of blood components, particularly with platelets concentrates (PCs) leukoreduced with negatively- charged filters. Bradykinin (BK)-related peptides were proposed as a possible cause of this side-effect. This study evaluated the effects of leukoreduction and storage conditions on the levels of two kinins (BK and des-Arg⁹-BK) in PCs.

METHODS. Whole blood donations (n=35) were processed using current PRP (platelet-rich plasma) procedure to prepare leukoreduced and unfiltered components by Leukotrap^® RC-PL Whole Blood Collection, Filtration and Storage System. PCs and plasma were stored for 7 days at 20–24°C with agitation. Levels of BK and des-Arg⁹-BK were measured by specific enzyme immunoassays and HPLC at day 0, 2, 5 and 7 of storage. Mechanisms potentially responsible for accumulation of BK and des-Arg⁹-BK were studied.

RESULTS. On day 0, kinins were measured in significantly higher concentrations in leukoreduced (BK: 101 ± 157 pg/mL; des-Arg⁹-BK: 194 ± 191 pg/mL) vs unfiltered PCs (BK: 71 ± 121 pg/mL; des-Arg⁹-BK: 98 ± 114 pg/mL). During storage, both kinins peaked on day 5, with concentrations higher than 1 ng/mL in 22% of leukoreduced as well as unfiltered PCs. Physicochemical and pharmacological characterization of immunoreactive kinins confirmed their nature. In vitro activation of the contact system of the corresponding platelet-poor plasma (PPP) showed that a high kinin concentration on day 5 of the storage corresponded to 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 activity 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. Our results indicate that filtration and storage conditions of PCs contribute to generation of pharmacologically relevant bradykinin levels that might pose a risk in susceptible patients. The clinical relevance of such high concentrations of kinins in PCs remains to be established but could potentially be significant especially in patients treated with angiotensin I-converting enzyme-inhibitors that affect the pathway of BK degradation.