Plasma Instead of Serum Avoids Critical Confounding of Clinical Metabolomics Studies by Platelets

Author(s)
Gerhard Hagn, Samuel M. Meier-Menches, Günter Plessl-Walder, Gaurav Mitra, Thomas Mohr, Karin Preindl, Andreas Schlatter, Doreen Schmidl, Christopher Gerner, Gerhard Garhöfer, Andrea Bileck
Abstract

Metabolomics is an emerging and powerful bioanalytical method supporting clinical investigations. Serum and plasma are commonly used without rational prioritization. Serum is collected after blood coagulation, a complex biochemical process involving active platelet metabolism. This may affect the metabolome and increase the variance, as platelet counts and function may vary substantially in individuals. A multiomics approach systematically investigating the suitability of serum and plasma for clinical studies demonstrated that metabolites correlated well (n = 461, R2 = 0.991), whereas lipid mediators (n = 83, R2 = 0.906) and proteins (n = 322, R2 = 0.860) differed substantially between specimen. Independently, analysis of platelet releasates identified most biomolecules significantly enriched in serum compared to plasma. A prospective, randomized, controlled parallel group metabolomics trial with acetylsalicylic acid administered for 7 days demonstrated that the apparent drug effects significantly differ depending on the analyzed specimen. Only serum analyses of healthy individuals suggested a significant downregulation of TXB2 and 12-HETE, which were specifically formed during coagulation in vitro. Plasma analyses reliably identified acetylsalicylic acid effects on metabolites and lipids occurring in vivo such as an increase in serotonin, 15-deoxy-PGJ2 and sphingosine-1-phosphate and a decrease in polyunsaturated fatty acids. The present data suggest that plasma should be preferred above serum for clinical metabolomics studies as the serum metabolome may be substantially confounded by platelets.

Organisation(s)
Department of Analytical Chemistry, Department of Inorganic Chemistry, Joint Metabolome Facility, Mass Spectrometry Centre
External organisation(s)
Vienna Doctoral School in Chemistry (DoSChem), Medizinische Universität Wien
Journal
Journal of Proteome Research
Volume
23
Pages
3064-3075
No. of pages
12
ISSN
1535-3893
DOI
https://doi.org/10.1021/acs.jproteome.3c00761
Publication date
03-2024
Peer reviewed
Yes
Austrian Fields of Science 2012
106037 Proteomics, 104002 Analytical chemistry
Keywords
ASJC Scopus subject areas
General Chemistry, Biochemistry
Portal url
https://ucrisportal.univie.ac.at/en/publications/784c6879-ce6d-4245-8a39-01f30f1032be