title: Random aggregates in newly produced platelet units are associated with platelet activation and release of the immunomodulatory factors sCD40L and RANTES.
abstract: BACKGROUND
  In connection with platelet (PLT) production, random but transient aggregates sometimes form in the newly produced units. The underlying mechanisms as well as the impact on cellular level of this phenomenon are unknown. Hypothetically, random occurrence of aggregates may induce biochemical changes leading to PLT activation and release of immunomodulatory factors from the PLTs.
  
  
  METHODS
  PLTs were aliquoted and prepared with an automated system for PLT pooling (OrbiSac, Terumo BCT) for a three-arm nonpaired study design (n=8). Initially aggregated PLT units in SSP+ were selected by visual inspection and compared to unaffected PLT units stored in SSP+ or 100% plasma. Cellular, metabolic, and functional variables were analyzed, including the concentrations of RANTES, sCD40L, and sTWEAK in the bags during a 9-day storage period.
  
  
  RESULTS
  Isolated aggregated PLTs show signs of spontaneous activation and respond less efficiently to TRAP stimulation. RANTES, sCD40L, and sTWEAK accumulated in the various PLT units during storage but sCD40L and RANTES accumulated in the initially aggregated PLT units to higher concentrations than the reference units and PLTs stored in 100% plasma (p<0.001). Over time, the levels of sTWEAK increased more in the plasma storage environment compared with PLT units stored in SSP+ (p<0.001).
  
  
  CONCLUSIONS
  Our data indicate that random occurrence of aggregates may lead to higher activation level and increased release of immunomodulatory factors from the PLTs.
authors.affiliation: Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital and Karolinska Institutet; Center for Hematology and Regenerative Medicine (HERM), Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Per
authors.initials: P
authors.lastname: Sandgren
authors.forename: Stephan
authors.initials: S
authors.lastname: Meinke
authors.forename: Elias
authors.initials: E
authors.lastname: Eckert
authors.forename: Iyadh
authors.initials: I
authors.lastname: Douagi
authors.forename: Agneta
authors.initials: A
authors.lastname: Wikman
authors.forename: Petter
authors.initials: P
authors.lastname: Höglund
mesh_terms: D001792:Blood Platelets / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism*; D006801:Humans; D056747:Immunomodulation / Q000502:physiology; D015539:Platelet Activation / Q000502:physiology*
chemical_list: D018946:Chemokine CCL5; D023201:CD40 Ligand