title: An association of soluble CD40 ligand (CD154) with adverse reactions to platelet transfusions.
abstract: BACKGROUND
  Removal of stored supernatant abrogates most transfusion reactions to leukoreduced platelets (PLTs), suggesting that PLT-derived soluble mediators are involved. PLTs are the primary source of soluble CD40 ligand (sCD40L). Engagement of the receptor for CD40L induces synthesis of proinflammatory mediators including interleukin (IL)-6, IL-8, and monocyte chemotactic protein-1 (MCP-1).
  
  
  METHODS
  Supernatants from poststorage leukoreduced PLT concentrates were assayed for white cell- (IL-6, IL-8, MCP-1) and PLT-derived (sCD40L, RANTES) inflammatory mediators. These levels were correlated with clinical outcomes.
  
  
  RESULTS
  Of 534 transfusions, there were 12 reported (2.2%) and 2 unreported reactions (0.4%)--10 febrile and 4 allergic. Transfusions with reactions had significantly higher levels of IL-6 (2.3-fold higher; p = 0.005), IL-8 (2.2-fold higher; p = 0.001), MCP-1 (2.6-fold higher; p = 0.002), and sCD40L (1.24-fold higher; p = 0.015), but not RANTES. (1.14-fold higher; p = 0.22). The vast majority (>93%) of patients transfused with mediator levels in the highest quintile had no reactions. When levels of all five mediators were summed, the reaction rates in the first through fifth quintiles increased from 1 to 7 percent (p = 0.027). All but one reaction occurred in patients with hematologic malignancies (13 reactions/380 transfusions; 3.4%; p = 0.04 vs. other diagnoses).
  
  
  CONCLUSIONS
  These are the first data demonstrating that a PLT-derived mediator, sCD40L, is associated with adverse transfusion events. Existing clinical factors, for example, inflammation or leukopenia, may influence whether infused mediators cause reactions.
authors.affiliation: Transfusion Medicine Unit and Clinical Laboratories, Department of Pathology and Laboratory Medicine, Hematology-Oncology Unit, the University of Rochester Medical Center, Rochester, New York 14642, USA. neil_blumberg@urmc.rochester.edu
authors.forename: Neil
authors.initials: N
authors.lastname: Blumberg
authors.forename: Kelly F
authors.initials: KF
authors.lastname: Gettings
authors.forename: Chantal
authors.initials: C
authors.lastname: Turner
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Heal
authors.forename: Richard P
authors.initials: RP
authors.lastname: Phipps
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism; D001793:Blood Preservation / Q000009:adverse effects / Q000379:methods; D023201:CD40 Ligand / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000378:metabolism / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D007970:Leukopenia / Q000150:complications / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017713:Platelet Transfusion / Q000009:adverse effects*; D011446:Prospective Studies
chemical_list: D016207:Cytokines; D023201:CD40 Ligand