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The pro‐inflammatory effects of platelet contamination in plasma and mitigation strategies for avoidance
Author(s) -
Bercovitz R. S.,
Kelher M. R.,
Khan S. Y.,
Land K. J.,
Berry T. H.,
Silliman C. C.
Publication year - 2012
Publication title -
vox sanguinis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.68
H-Index - 83
eISSN - 1423-0410
pISSN - 0042-9007
DOI - 10.1111/j.1423-0410.2011.01559.x
Subject(s) - platelet , cytotoxicity , platelet rich plasma , platelet activation , chemistry , priming (agriculture) , whole blood , immunology , platelet poor plasma , centrifugation , pharmacology , andrology , medicine , in vitro , biochemistry , biology , germination , botany
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 (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. 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.