High-density lipoprotein 3 and apolipoprotein A-I alleviate platelet storage lesion and release of platelet extracellular vesicles

Transfusion. 2014 Sep;54(9):2301-14. doi: 10.1111/trf.12640. Epub 2014 Jun 10.


Background: Stored platelet (PLT) concentrates (PLCs) for transfusion develop a PLT storage lesion (PSL), decreasing PLT viability and function with profound lipidomic changes and PLT extracellular vesicle (PL-EV) release. High-density lipoprotein 3 (HDL3 ) improves PLT homeostasis through silencing effects on PLT activation in vivo. This prompted us to investigate HDL3 and apolipoprotein A-I (apoA-I) as PSL-antagonizing agents.

Study design and methods: Healthy donor PLCs were split into low-volume standard PLC storage bags and incubated with native (n)HDL3 or apoA-I from plasma ethanol fractionation (precipitate IV) for 5 days under standard blood banking conditions. Flow cytometry, Born aggregometry, and lipid mass spectrometry were carried out to analyze PL-EV release, PLT aggregation, agonist-induced PLT surface marker expression, and PLT and plasma lipid compositions.

Results: Compared to control, added nHDL3 and apoA-I significantly reduced PL-EV release by up to -62% during 5 days, correlating with the added apoA-I concentration. At the lipid level, nHDL3 and apoA-I antagonized PLT lipid loss (+12%) and decreased cholesteryl ester (CE)/free cholesterol (FC) ratios (-69%), whereas in plasma polyunsaturated/saturated CE ratios increased (+3%) and CE 16:0/20:4 ratios decreased (-5%). Administration of nHDL3 increased PLT bis(monoacylglycero)phosphate/phosphatidylglycerol (+102%) and phosphatidic acid/lysophosphatidic acid (+255%) ratios and improved thrombin receptor-activating peptide 6-induced PLT aggregation (+5%).

Conclusion: nHDL3 and apoA-I improve PLT membrane homeostasis and intracellular lipid processing and increase CE efflux, antagonizing PSL-related reduction in PLT viability and function and PL-EV release. We suggest uptake and catabolism of nHDL3 into the PLT open canalicular system. As supplement in PLCs, nHDL3 or apoA-I from Fraction IV of plasma ethanol fractionation have the potential to improve PLC quality to prolong storage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein A-I / pharmacology*
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism*
  • Blood Preservation / adverse effects
  • Cell Survival / physiology
  • Flow Cytometry
  • Humans
  • In Vitro Techniques
  • Lipoproteins, HDL3 / pharmacology*
  • Platelet Activation
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Function Tests
  • Platelet-Rich Plasma


  • Apolipoprotein A-I
  • Lipoproteins, HDL3
  • Platelet Aggregation Inhibitors