title: HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management.
abstract: Approximately five decades ago, alloimmunization to human leukocyte antigens (HLA) and platelet refractoriness were recognized as potentially serious complications of platelet transfusions. The mechanisms that result in stimulating immunity against blood products are still incompletely understood but are related to both the composition of the donor product transfused and the immune status of the recipient. Based on murine studies of platelet immunity, platelets are inherently immunogenic and there are at least two independent levels of immunoregulation against platelet transfusions. The first level resides within the recipient and is related to antigen processing/presentation events and CD8+ T cell-mediated immunosuppression. The second level relates to the donor product and includes donor antigen presenting cells (APC) levels as well as age-induced changes in donor APC and/or platelets. Implementation of pre-storage leukoreduction of cellular blood components led to a marked reduction in platelet alloimmunization and its dreaded complication, platelet refractoriness. Platelet refractoriness is usually managed by transfusion of matched platelets, selected according to one of the many published methods. It is unclear which of these methods is superior, and given the difficulty of obtaining a perfectly matched product, perhaps the most logical approach is to use a combination of selection strategies. This review discusses the various aspects of platelet alloimmunization and the clinical consequences that may result. It highlights how animal studies have shed light on the immune mechanisms responsible for allogeneic platelet immunity and immunomodulation and reviews relevant literature on clinical and laboratory manifestations of immune platelet refractoriness.
authors.affiliation: Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. pavenskik@smh.ca
authors.forename: Katerina
authors.initials: K
authors.lastname: Pavenski
authors.forename: John
authors.initials: J
authors.lastname: Freedman
authors.forename: J W
authors.initials: JW
authors.lastname: Semple
mesh_terms: D000818:Animals; D006084:Graft Rejection / Q000503:physiopathology* / Q000517:prevention & control* / Q000628:therapy; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D017713:Platelet Transfusion / Q000009:adverse effects*
chemical_list: D006680:HLA Antigens; D007519:Isoantigens