FRABETTI ET AL. 160 TRANSFUSION Volume 40, February 2000 B L O O D C O M P O N E N T S A poptosis is a form of genetically encoded, pro- grammed cell death that plays an essential role in development, homeostasis, and defense in multicellular organisms. 1-4 From a morphologic point of view, it consists of nuclear fragmentation, blebbing, and, finally, cell disruption with the formation of character- istic “apoptotic bodies.” All these cell-derived fragments are, in physiologic conditions, readily captured by phago- cytes without any sign of inflammation. In vitro causes of apoptosis are manifold and include irradiation, serum dep- rivation, and additives in the medium. Little is known in transfusion medicine about the changes in white cells (WBCs) due to continuous storage of blood components, mainly packed red cells (RBCs) and platelet concentrates (PCs). In regard to RBCs, we demonstrated in a previous study that conditions of storage (i.e., 1-6°C) of packed RBC units induce consistent and massive apoptosis in residual WBCs, as evaluated by three methods. 5 To our knowledge, WBC apoptosis occurring in PCs used in transfusion has not so far been studied or quantified. In fact, different storage conditions than are used for RBCs (i.e., White cell apoptosis in platelet concentrates F. Frabetti, P.L. Tazzari, D. Musiani, A. Bontadini, C. Matteini, L. Roseti, C. Tassi, M. Viggiani, M. Marini, and R. Conte BACKGROUND: The aim of the present study was the evaluation of the apoptosis in residual white cells (WBCs) contained in platelet concentrates (PCs) and of the relationship of this apoptosis with the concentration of inflammatory cytokines in the medium and with plate- let activation. STUDY DESIGN AND METHODS: Three independent methods were used to evaluated apoptosis in WBCs present in 9 PCs, either from single donors by apheresis (SD-PCs) or from pooled buffy coats (BC-PCs). All PCs were divided in two parts, one of which was irradiated. PCs were stored up to 4 days at room temperature, and samples were withdrawn daily for analysis of apoptosis, of platelet activation (surface and soluble CD62P), and of cytokine concentration (interleukin [IL]-1α, IL-1β, IL-6, IL-8, and tumor necrosis factor α). RESULTS: Apoptosis was found to occur with storage in both irradiated and nonirradiated units. Platelet activa- tion increased with storage time and was higher in BC- PCs. The amount of released cytokines was rather vari- able among PC units. Only IL-8 was consistently found to increase with storage time. CONCLUSIONS: Apoptosis of residual WBCs occurred in PC units as a function of storage time. The amount and the time course of apoptosis seem to correlate with IL-8 release rather than with platelet activation or with the occurrence of febrile nonhemolytic transfusion reac- tions. ABBREVIATIONS: BC-PC(s) = PC(s) obtained from buffy coats; ELISA = enzyme-linked immunosorbent assay; FITC = fluores- cein isothicyanate; IL = interleukin; PC(s) = platelet concentrate(s); PE = phycoerythrin; PI = propidium iodide; RBC(s) = red cell(s); sCD62P = soluble CD62P; SD-PC(s) = PC(s) obtained by apheresis from single donors; TNFα = tumor necro- sis factor α; WBC(s) = white cell(s). From the Immunohematology and Transfusion Service, Policlinico S. Orsola, and the Institute for Histology and General Embryology, University of Bologna, Bologna, Italy. Address reprint requests to: Roberto Conte, MD, Servizio di Immunoematologia e Trasfusionale, Policlinico S. Orsola- Malpighi, Via Massarenti 9, 40138 Bologna, Italy; e-mail: trasfusionale@orsola-malpighi.med.unibo.it. Supported in part by the Istituto Superiore di Sanità, within the framework of “Progetto Sangue.” Received for publication February 10, 1999; revision re- ceived June 1, 1999, and accepted June 7, 1999. TRANSFUSION 2000;40:160-168.