OA2-AM24-MN-14 - Characterization of the Stored Platelet Unit Lipidome and its Relationship to Donor Sex and Hemostatic Function

Cold-stored platelets (CS-PLT) maintain improved hemostatic function at longer storage durations over standard room temperature-stored PLT (RT-PLT). However, the exact mechanisms regulating preserved hemostatic function CS-PLT are not fully defined. As the circulating lipidome is known to play a critical role in platelet activation and primary hemostasis, our objective was to identify how the PLT lipidome impacts hemostatic function.

Study

Design/Methods:

Apheresis PLT were collected via Trima Accel 7 and stored in 100% plasma (N=8; donor N_female=5, N_male=3). Units were sampled post-collection, stored at 22C for 7 days or 4C for 21 days, and sampled weekly. Mass spectrometry lipidomics was performed on platelet-poor plasma samples derived from units at each timepoint and storage condition. Hemostatic function was assessed via light transmission aggregometry (LTA) and rotational viscoelastometry (ROTEM). Lipid ontology was performed using LION/web. Lipidomic profiling was performed using p</span>artial least squares-discriminant analysis (PLS-DA) and Metaboanalyst. Functional data was analyzed via 2-way ANOVA with multiple comparisons, and principal component analysis (PCA) was used to interrogate relationships between lipidomic and functional data.

Results/Findings:

PLS-DA revealed that donor sex was most associated with distinct lipid profiles as compared to storage temperature or duration (FigA1-5), and with a higher accuracy (0.89; R² = 0.87; Q² = 0.77 at 2 principal components) (FigA6). PCA revealed that donor sex (FigA7) most strongly identified lipidomic and functional profiles amongst donors as compared to storage temperature and duration; PC2 discriminated sex differences with the highest positive (female) loading vector being ExTEM CFT (0.47) and the highest negative (male) loading vector being donor hematocrit (-0.82). Extrapolating from these findings, we found CS-PLT from male donors (N=3) had reduced aggregation in response to ADP + Collagen and delayed clotting times via ROTEM over the course of storage (N=5). Male donors overall were found to have more diminished function when comparing d0 to d21 for CS and d7 for RT (FigA10). Spearman correlation of lipidomic and functional data revealed sex-specific significant correlations (FigA8,9), and those lipids associated with female donors were represented by lipids with positive intrinsic curvature and headgroups with negative charges.

Conclusions:

The lipid content in stored PLT are more likely to be impacted by their respective donor sex instead of by storage temperature or duration. We found significant sex-specific correlations between lipids and hemostatic function. This suggests intrinsic, sex-based differences in lipid profiles of CS-PLT remain unchanged in different storage conditions across time and these profiles may contribute to the overall hemostatic function in stored PLT.