Metabolic tracing analysis reveals substrate-specific metabolic deficits in platelet storage lesion

Transfusion. 2017 Nov;57(11):2683-2689. doi: 10.1111/trf.14292. Epub 2017 Aug 23.

Abstract

Background: Storage of platelets (PLTs) results in a progressive defect termed PLT storage lesion (PSL). The PSL is characterized by poor PLT quality on a variety of assays. Metabolic defects are thought to underlie the PSL; thus this study was designed to quantitatively probe specific metabolic pathways over PLT storage.

Study design and methods: Relative incorporation of stable isotope-labeled substrates was quantified by isotopologue analysis of key acyl-coenzyme A (CoA) thioester products for fresh, viable (after collection, Days 2-5), and expired PLTs (after Day 5). We examined the incorporation of acetate, glucose, and palmitate into acetyl- and succinyl-CoA via liquid chromatography-tandem mass spectrometry.

Results: Storage-related defects in the incorporation of acetyl-CoA derived from acetate and palmitate were observed. Carbon derived from palmitate and acetate in succinyl-CoA was reduced over storage time. Glucose incorporation into succinyl-CoA increased in viable PLTs and then decreased in expired PLTs. Carbon derived from octanoate and pyruvate remained partially able to incorporate into acetyl- and succinyl-CoA in expired PLTs, with high variability in pyruvate incorporation.

Conclusion: Isotopologue analysis is useful in probing substrate specific defects in the PSL.

MeSH terms

  • Acetates / metabolism
  • Acyl Coenzyme A / metabolism
  • Blood Platelets / metabolism*
  • Blood Preservation / standards*
  • Carbon Isotopes
  • Chromatography, Liquid
  • Glucose / metabolism
  • Humans
  • Isotope Labeling
  • Mass Spectrometry
  • Metabolic Networks and Pathways*
  • Palmitates / metabolism

Substances

  • Acetates
  • Acyl Coenzyme A
  • Carbon Isotopes
  • Palmitates
  • succinyl-coenzyme A
  • Glucose