PMID- 26446055 OWN - NLM STAT- MEDLINE DCOM- 20160701 LR - 20160211 IS - 1537-2995 (Electronic) IS - 0041-1132 (Linking) VI - 56 IP - 2 DP - 2016 Feb TI - Platelet components associated with adverse reactions: predictive value of mitochondrial DNA relative to biological response modifiers. PG - 497-504 LID - 10.1111/trf.13373 [doi] AB - BACKGROUND: Biological response modifiers (BRMs), secreted by platelets (PLTs) during storage, play a role in adverse events (AEs) associated with transfusion. Moreover, mitochondrial DNA (mtDNA) levels in PLT components (PCs) are associated with AEs. In this study we explore whether there is a correlation between pathogenic BRMs and mtDNA levels and whether these markers can be considered predictors of transfusion pathology. STUDY DESIGN AND METHODS: We investigated a series of reported AEs after PC transfusion, combining clinical observations and mathematical modeling systems. RESULTS: mtDNA was consistently released during the first days of PC storage; however, mtDNA release was earlier in "pathogenic" than in nonpathogenic PCs. PC supernatants with high levels of mtDNA along with soluble CD40 ligand (sCD40L) were significantly associated with occurrences of AEs. The fact that mtDNA did not associate with the 14 BRMs tested suggests the role of mtDNA in PC transfusion-linked inflammation is independent of that of BRMs, known to be associated with AEs. We present evidence that PLTs generate distinct pathogenic secretion profiles of BRMs and mtDNA. The calculated area under the curve for mtDNA was significantly associated with AEs, although less stringently predictive than those of sCD40L or interleukin-13, standard predictors of AE. The established model predicts that distinct subtypes of AEs can be distinguished, dependent on mtDNA levels and PC storage length. CONCLUSIONS: Further work should be considered to test the propensity of mtDNA in PLT concentrates to generate inflammation and cause an AE. CI - (c) 2015 AABB. FAU - Cognasse, Fabrice AU - Cognasse F AD - Etablissement Francais du Sang Auvergne-Loire, Saint-Etienne. AD - GIMAP-EA3064, Universite de Lyon, Saint-Etienne, France. FAU - Aloui, Chaker AU - Aloui C AD - GIMAP-EA3064, Universite de Lyon, Saint-Etienne, France. FAU - Anh Nguyen, Kim AU - Anh Nguyen K AD - GIMAP-EA3064, Universite de Lyon, Saint-Etienne, France. FAU - Hamzeh-Cognasse, Hind AU - Hamzeh-Cognasse H AD - GIMAP-EA3064, Universite de Lyon, Saint-Etienne, France. FAU - Fagan, Jocelyne AU - Fagan J AD - Etablissement Francais du Sang Auvergne-Loire, Saint-Etienne. FAU - Arthaud, Charles-Antoine AU - Arthaud CA AD - Etablissement Francais du Sang Auvergne-Loire, Saint-Etienne. FAU - Eyraud, Marie-Ange AU - Eyraud MA AD - Etablissement Francais du Sang Auvergne-Loire, Saint-Etienne. FAU - Sebban, Marc AU - Sebban M AD - Laboratoire Hubert Curien, UMR CNRS 5516, Saint-Etienne. FAU - Fromont, Elisa AU - Fromont E AD - Laboratoire Hubert Curien, UMR CNRS 5516, Saint-Etienne. FAU - Pozzetto, Bruno AU - Pozzetto B AD - GIMAP-EA3064, Universite de Lyon, Saint-Etienne, France. FAU - Laradi, Sandrine AU - Laradi S AD - Etablissement Francais du Sang Auvergne-Loire, Saint-Etienne. AD - GIMAP-EA3064, Universite de Lyon, Saint-Etienne, France. FAU - Garraud, Olivier AU - Garraud O AD - GIMAP-EA3064, Universite de Lyon, Saint-Etienne, France. AD - INTS-Institut National de la Transfusion Sanguine, Paris, France. LA - eng PT - Clinical Trial PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20151007 PL - United States TA - Transfusion JT - Transfusion JID - 0417360 RN - 0 (DNA, Mitochondrial) RN - 0 (Interleukin-13) RN - 147205-72-9 (CD40 Ligand) SB - IM MH - Blood Platelets/*metabolism MH - Blood Preservation/*adverse effects MH - CD40 Ligand/*metabolism MH - DNA, Mitochondrial/*metabolism MH - Female MH - Humans MH - Interleukin-13/*metabolism MH - Male MH - Platelet Transfusion/*adverse effects MH - Time Factors EDAT- 2015/10/09 06:00 MHDA- 2016/07/02 06:00 CRDT- 2015/10/09 06:00 PHST- 2015/05/12 00:00 [received] PHST- 2015/07/23 00:00 [revised] PHST- 2015/08/31 00:00 [accepted] PHST- 2015/10/09 06:00 [entrez] PHST- 2015/10/09 06:00 [pubmed] PHST- 2016/07/02 06:00 [medline] AID - 10.1111/trf.13373 [doi] PST - ppublish SO - Transfusion. 2016 Feb;56(2):497-504. doi: 10.1111/trf.13373. Epub 2015 Oct 7.