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Use of Specialized Pro-Resolving Mediators to Alleviate Cold Platelet Storage Lesion.

Authors
  • Reddoch-Cardenas, Kristin M1
  • Sharma, Umang1
  • Salgado, Christi L1
  • Cantu, Carolina1
  • Darlington, Daniel N1
  • Pidcoke, Heather F2
  • Bynum, James A1
  • Cap, Andrew P1
  • 1 Coagulation and Blood Research Program, U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas, USA.
  • 2 Translational Medicine Institute, Colorado State University, Fort Collins, Colorado, USA.
Type
Published Article
Journal
Transfusion
Publisher
Wiley (Blackwell Publishing)
Publication Date
Jun 01, 2020
Volume
60 Suppl 3
Identifiers
DOI: 10.1111/trf.15750
PMID: 32478925
Source
Medline
Language
English
License
Unknown

Abstract

Cold-stored platelets are an attractive option for treatment of actively bleeding patients due to a reduced risk of septic complications and preserved hemostatic function compared to conventional room temperature-stored platelets. However, refrigeration causes increased platelet activation and aggregate formation. Specialized pro-resolving mediators (SPMs), cell signaling mediators biosynthesized from essential fatty acids, have been shown to modulate platelet function and activation. In this study, we sought to determine if SPMs could be used to inhibit cold-stored platelet activation. Platelets were collected from healthy donors (n = 4-7) and treated with SPMs (resolvin E1 [RvE1], maresin 1 [MaR1], and resolvin D2 [RvD2]) or vehicle (VEH; 0.1% EtOH). Platelets were stored without agitation in the cold and assayed on Days 0 and 7 of storage for platelet activation levels using flow cytometry, platelet count, aggregation response using impedance aggregometry, and nucleotide content using mass spectrometry. Compared to VEH, SPM treatment inhibited GPIb shedding (all compounds), significantly reduced both PS exposure and activation of GPIIb/IIIa receptor (RvD2, MaR1), and preserved aggregation response to TRAP (RvD2, MaR1) after 7 days of storage. Similar to untreated cold-stored platelets, SPM-treated samples did not preserve platelet counts or block the release of P-Selectin. Nucleotide content was unaffected by SPM treatment in cold-stored platelets. SPM treatment, particularly Mar1 and RvD2, led to reduced platelet activation and preserved platelet function after 7 days of storage in the cold. Future work is warranted to better elucidate the mechanism of action of SPMs on cold platelet function and activation. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.

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