van Wonderen Stefan F, van Baarle Floor L F, Phelp Philippa G, Bulle Esther B, Argabright Amy, de Bruin Sanne, Tuip-de Boer Anita M, Polet Chantal A, van Amstel Rombout B E, Lim Endry H T, Schenk Jimmy, Peters Anna-Linda, van Bruggen Robin, Reisz Julie A, Vermeulen Christie, Klei Thomas R L, Biemond Bart J, Müller Marcella C A, D'Alessandro Angelo, Vlaar Alexander P J
Department of Intensive Care, Amsterdam University Medical Center location University of Amsterdam, Amsterdam, The Netherlands.
Laboratory of Experimental Intensive Care and Anesthesiology, Amsterdam University Medical Center location University of Amsterdam, Amsterdam, The Netherlands.
Blood Adv. 2025 Oct 28;9(20):5164-5176. doi: 10.1182/bloodadvances.2025016853.
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- and long-term stored PCs during controlled inflammation, focusing on distinct metabolic pathways, alterations in surface markers and posttransfusion recovery (PTR). Twenty-four male participants received lipopolysaccharide or saline as control after an autologous transfusion of either short- (2 days) or long-term (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. Before transfusion, short-term stored PCs demonstrated increased glycolysis, pentose phosphate pathway activity, dense granule components (eg, serotonin, adenosine diphosphate, and 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- 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 the International Clinical Trials Registry Platform (https://trialsearch.who.int/) as #NL-OMON26852.
血小板浓缩物（PCs）常用于预防和治疗患者出血。然而，在炎症期间以及由于血小板储存损伤，包括代谢组学变化和储存的PCs表面标志物的改变，其疗效会降低。本研究旨在确定在可控炎症期间短期和长期储存的PCs之间的差异，重点关注不同的代谢途径、表面标志物的改变和输血后恢复（PTR）。24名男性参与者在自体输注短期（2天）或长期（7天）储存的PCs后，接受脂多糖或生理盐水作为对照。分别使用质谱和流式细胞术在输血前评估这些输注的PCs的代谢组学和表面标志物。生物素标记的血小板用于评估输血后的表面标志物并确定PTR。输血前，短期储存的PCs表现出糖酵解增加、磷酸戊糖途径活性增强、致密颗粒成分（如5-羟色胺、二磷酸腺苷和肾上腺素）以及嘌呤、精氨酸和色氨酸代谢增加。相比之下，长期储存的PCs表现出转硫作用和牛磺酸代谢升高，以及更高水平的CD62P和CD63。在炎症期间，发现PTR降低，尤其是在长期储存的PCs中。致密颗粒代谢物成分的高表达以及较低的CD62P和乳酸水平与改善的PTR相关。在一项可控的人体实验中，确定了短期和长期储存的PCs在代谢途径、表面标志物和PTR方面的差异，表明在炎症期间倾向于使用短期储存的PCs。该试验已在国际临床试验注册平台（https://trialsearch.who.int/）注册，注册号为#NL-OMON26852。
