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

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.