Plasma Instead of Serum Avoids Critical Confounding of Clinical Metabolomics Studies by Platelets, 2024, Hagn et al.

[SNT Gatchaman]

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

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.

Link | PDF (Journal of Proteome Research) [Open Access]

 

[SNT Gatchaman]

Clinical metabolomics is typically performed using serum or plasma as sample matrices. The preparation of serum implies blood coagulation before centrifuging off the particular part of the full blood. In contrast, blood coagulation is inhibited on purpose by adding an anticoagulant to obtain plasma. As blood coagulation implies the functional activation of platelets, some differences in the metabolome composition of serum and plasma may be expected.

Here we suggest that plasma metabolomics may be better suitable for clinical studies than serum metabolomics as plasma data will not suffer from additional variance introduced by varying platelet counts as well as differing platelet states and data will not be confounded by platelet metabolism affected during blood coagulation.