Abstract

Background - The impact of donor biology on blood component storability is increasingly appreciated as a determinant of the storage lesion and post-transfusion performances. Platelet metabolism is affected by age and it is critical to platelet responses to activating stimuli in an age-dependent manner. Sex has been previously highlighted as a contributing factor to the platelet proteomics lesion. However, little is known about the impact of donor sex and age on stored platelet metabolism and post-transfusion capacity to circulate.
Materials and methods - Apheresis platelets were donated via apheresis by 21 healthy volunteers (12 males and 9 females; ages 20 to 59). Metabolomics analyses were performed at day 0 and after 5 days of storage at 22+2 °C, along with autologous post-transfusion recovery and survival studies with 51Cr and 111In.
Results - Sex and age significantly impacted platelet metabolism at baseline and upon storage. Platelets from older, male donors were characterised by higher levels of Krebs cycle metabolites, pentose phosphate pathway intermediates and byproducts, deaminated purines and long chain fatty acids. These metabolites ranked amongst the top significant correlates to post-transfusion recoveries. Glutathione homeostasis and sphingosine 1-phosphate were the top positive correlates to long term survival, which was lower in platelets from older, male donors – without reaching statistical significance.
Discussion - In this study we report that donor sex and age have a significant impact on platelet metabolism. Novel metabolic correlates to platelet post-transfusion performances (24 h recovery and long-term survival) were identified through
high-resolution, stable isotope-labeled internal standard-assisted metabolomics approach.

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Authors

Angelo D’Alessandro - Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States of America; Department of Medicine, Division of Haematology, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States of America

Davide Stefanoni - Department of Biochemistry and Molecular Genetics, University of Colorado Denver - Anschutz Medical Campus, Aurora, CO, United States of America

Sherrill J. Slichter - Department of Internal Medicine, Division of Haematology, University of Washington School of Medicine - Seattle, WA, United States of America; BloodWorks Northwest Research Institute, Seattle, WA, United States of America

Xiaoyun Fu - BloodWorks Northwest Research Institute, Seattle, WA, United States of America

James C. Zimring - Department of Pathology, University of Virginia, Charlotesville, VA, United States of America

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