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.
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.
Authors: Pearl Toy; Mark A Popovsky; Edward Abraham; Daniel R Ambruso; Leslie G Holness; Patricia M Kopko; Janice G McFarland; Avery B Nathens; Christopher C Silliman; David Stroncek Journal: Crit Care Med Date: 2005-04 Impact factor: 7.598
Authors: Samina Yasmin Khan; Marguerite R Kelher; Joanna M Heal; Neil Blumberg; Lynn K Boshkov; Richard Phipps; Kelly F Gettings; Nathan J McLaughlin; Christopher C Silliman Journal: Blood Date: 2006-06-13 Impact factor: 22.113
Authors: G R Bernard; A Artigas; K L Brigham; J Carlet; K Falke; L Hudson; M Lamy; J R LeGall; A Morris; R Spragg Journal: J Crit Care Date: 1994-03 Impact factor: 3.425
Authors: C C Silliman; N F Voelkel; J D Allard; D J Elzi; R M Tuder; J L Johnson; D R Ambruso Journal: J Clin Invest Date: 1998-04-01 Impact factor: 14.808
Authors: Michele M Loi; Marguerite Kelher; Monika Dzieciatkowska; Kirk C Hansen; Anirban Banerjee; F Bernadette West; Crystal Stanley; Matthew Briel; Christopher C Silliman Journal: Transfusion Date: 2018-09-01 Impact factor: 3.157
Authors: Christopher C Silliman; Marguerite R Kelher; Samina Y Khan; Monica LaSarre; F Bernadette West; Kevin J Land; Barbara Mish; Linda Ceriano; Samuel Sowemimo-Coker Journal: Blood Date: 2014-04-18 Impact factor: 22.113
Authors: M Dzieciatkowska; C C Silliman; E E Moore; M R Kelher; A Banerjee; K J Land; M Ellison; F B West; D R Ambruso; K C Hansen Journal: Vox Sang Date: 2013-05-11 Impact factor: 2.144