Bioactive lipids accumulate in stored red blood cells despite leukoreduction: a targeted metabolomics study

Accumulation of bioactive lipids during red blood cell (RBC) storage has been identified as a potential source of posttransfusion sequelae in vulnerable populations. Typically, white blood cells (WBCs) have been implicated in the generation of bioactive lipids, and leukoreduction has been seen as a solution to this issue.

We developed a targeted metabolomics approach with isotope dilution to quantify a panel of bioactive lipids in both leukoreduced (LR) and nonleukoreduced (NLR) RBC units over the course of storage.

Leukoreduction greatly attenuated the production of 12-hydroxyeicosatetraenoic acid (HETE), 12-hydroxyeicosapentaenoic acid, and 14-hydroxydocosahexaenoic acid (HDoHE), all three of which are mediated by 12-lipoxygenase present in WBCs and platelets. However, despite leukoreduction, micromolar levels of linoleic acid (LA), arachidonic acid (AA), and docosahexaenoic acid (DHA) were observed in the RBC units stored for 42 days. These major polyunsaturated fatty acids (PUFAs) and their oxidation products (oxylipins) also significantly increased with storage time, including 5-, 8-, 9-, 11-, 12-, and 15- HETEs from AA; 9- and 13-hydroxyoctadecadienoic acid (HODE); 9-, 10-, and 12,13-dihydroxyoctadecenoic acids from LA; and 14-, 16-, and 17-HDoHEs from DHA. The majority of PUFAs and oxylipins accumulated in the supernatant fraction. Large donor-to-donor variations were observed in both LR-RBC and NLR-RBC units.

While the exact role the accumulation of PUFAs and oxylipins plays in RBC unit quality and transfusion medical outcomes remains undetermined, the analytes of interest in this study may serve as biomarkers for lipid degradation and oxidation during storage and may induce changes in human physiology upon transfusion.