EFFECT OF FILTRATION OF PLATELET CONCENTRATES ON THE ACCUMULATION OF CYTOKINES AND PLATELET-RELEASE FACTORS DURING STORAGE

Background: Platelet transfusions are frequently accompanied by febril e nonhemolytic transfusion reactions. These may be due, in part, to th e release of cytokines interleukin 1 beta (IL-1 beta), interleukin 6 ( IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alph a) by white cells (WBCs) into the plasma during storage of platelet co ncentrates (PCs). Acting as endogenous pyrogens, these agents may indu ce inflammatory responses. Study Design and Methods:This study propose d to determine if WBC reduction in PCs by filtration significantly red uced the levels of cytokines normally generated during storage of unfi ltered PCs up to 5 days. Serotonin, platelet-derived growth factor (PD GF-AB), and von Willebrand factor levels were also assessed to establi sh whether or not filtration or storage elicited significant platelet activation and granule release. Results: Filtration significantly redu ced total WBC counts by 99.1 percent before storage (p<0.001) without affecting total platelet counts. Compared to unfiltered PCs, filtratio n prevented rise in the levels of each cytokine by Day 3 for IL-1 beta (27.7 vs. 0.6 pg/mL; p<0.05), IL-6 (114.2 vs. 0.4 pg/mL; p<0.001), an d IL-8 (4.2 vs. 0.02 ng/mL; p<0.001). By Day 5, further increases in t he levels of all cytokines were noted in unfiltered PCs, but Day 0 lev els remained in filtered PCs (IL-1 beta: 105.4 vs. 0.4 pg/mL, p<0.001; TNF-alpha: 42.2 vs. 7.5 pg/mL, p<0.025; IL-6: 268.8 vs. 0.4 pg/mL, p<0 .001; and IL-8: 7.6 vs. 0.02 ng/mL, p<0.001). From Day 0 to Day 5, the re were significant increases in serotonin (21.3 vs. 6.3 ng/mL, p<0.05 ), PDGF-AB (72.6 vs. 25.8 ng/mL, p<0.001), and von Willebrand factor ( 4.7 vs. 2.7 IU/mL, p<0.05) in unfiltered PCs, with similar increased l evels being observed in filtered PCs during storage. Conclusion: These data indicate that the accumulation of high levels of cytokines in st ored PCs could be prevented by WBC-reduction filtration of PCs without the induction of significant platelet activation or granule release. As cytokines have the potential to induce febrile nonhemolytic transfu sion reactions in patients, the transfusion of WBC-reduced PCs would b e expected to reduce the frequency and severity of such reactions.