Post-transfusion recovery, quality and metabolism of short and long-term stored platelets during controlled inflammation.

Abstract

Platelet concentrates (PCs) are frequently used to prevent and treat bleeding in patients. However, their efficacy is reduced during inflammation as well as due to platelet storage lesion, including metabolomic shifts and changes in surface markers of stored PCs. This study aims to identify disparities between short-term and long-term stored PCs during controlled inflammation, focusing on distinct metabolic pathways, alterations in surface markers and post-transfusion recovery (PTR). Twenty-four male subjects received lipopolysaccharide (LPS) or saline as control following an autologous transfusion of either short-term (2 days stored) or long-term stored (7 days stored) PCs. Metabolomics and surface markers of these transfused PCs were assessed before transfusion using mass spectrometry and flow cytometry, respectively. Biotin-labeled platelets were used to assess surface markers after transfusion and determine PTR. Prior to transfusion, short-term stored PCs demonstrated increased glycolysis, pentose phosphate pathway activity, dense granule components (e.g., serotonine, adenosine diphosphate, epinephrine), and purine, arginine, and tryptophan metabolism. In contrast, long-term stored PCs exhibited elevated transsulfuration and taurine metabolism, along with higher levels of CD62P and CD63. During inflammation, a decreased PTR was found, particularly in long-term stored PCs. Higher expression of dense granule metabolite components and lower CD62P and lactate levels were correlated with improved PTR. Differences in metabolic pathways, surface markers, and PTR were identified between short-term and long-term stored PCs in a controlled human experiment - suggesting a preference for the use of short-term stored PCs during inflammation. This trial was registered at https://trialsearch.who.int/ as #NL-OMON26852.