title: The pro-inflammatory effects of platelet contamination in plasma and mitigation strategies for avoidance.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Plasma was untreated, centrifuged (12,500 g) or separated from leucoreduced whole blood (WBLR) prior to freezing. Platelet counts and sCD40L concentrations were measured 1-5 days 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Bonfils Blood Center, Denver, CO, USA. bercovitz.rachel@tchden.org
authors.forename: R S
authors.initials: RS
authors.lastname: Bercovitz
authors.forename: M R
authors.initials: MR
authors.lastname: Kelher
authors.forename: S Y
authors.initials: SY
authors.lastname: Khan
authors.forename: K J
authors.initials: KJ
authors.lastname: Land
authors.forename: T H
authors.initials: TH
authors.lastname: Berry
authors.forename: C C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology*; D001792:Blood Platelets / Q000382:microbiology / Q000473:pathology*; D023201:CD40 Ligand / Q000097:blood; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D018375:Neutrophil Activation; D009504:Neutrophils; D065227:Transfusion Reaction
chemical_list: D023201:CD40 Ligand
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