The pro-inflammatory effects of platelet contamination in plasma and mitigation strategies for avoidance

R. S. Bercovitz*, M. R. Kelher, S. Y. Khan, K. J. Land, T. H. Berry, C. C. Silliman

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Background and Objectives Plasma and platelet concentrates are disproportionately implicated in transfusion-related acute lung injury (TRALI). Platelet-derived pro-inflammatory mediators, including soluble CD40 ligand (sCD40L), accumulate during storage. We hypothesized that platelet contamination induces sCD40L generation that causes neutrophil [polymorphonuclear leucocyte (PMN)] priming and PMN-mediated cytotoxicity. Materials and Methods Plasma was untreated, centrifuged (12500g) or separated from leucoreduced whole blood (WBLR) prior to freezing. Platelet counts and sCD40L concentrations were measured 1-5days post-thaw. The plasma was assayed for PMN priming activity and was used in a two-event in vitro model of PMN-mediated human pulmonary microvascular endothelial cell (HMVEC) cytotoxicity. Results Untreated plasma contained 42±4·2×10 3/μl platelets, which generated sCD40L accumulation (1·6-eight-fold vs. controls). Priming activity and HMVEC cytotoxicity were directly proportional to sCD40L concentration. WBLR and centrifugation reduced platelet and sCD40L contamination, abrogating the pro-inflammatory potential. Conclusion Platelet contamination causes sCD40L accumulation in stored plasma that may contribute to TRALI. Platelet reduction is potentially the first TRALI mitigation effort in plasma manufacturing.

Original languageEnglish (US)
Pages (from-to)345-353
Number of pages9
JournalVox Sanguinis
Volume102
Issue number4
DOIs
StatePublished - May 2012

Keywords

  • Plasma
  • SCD40L
  • Transfusion-related acute lung injury

ASJC Scopus subject areas

  • Hematology

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