Tissue Antigens ISSN 0001-2815
REVIEW ARTICLE
HLA alloimmunization against platelet transfusions: pathophysiology, significance, prevention and management Katerina Pavenski1,2 , John Freedman1,2,3,4, & J. W. Semple1,2,3,4,5,6 1 Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada 2 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada 3 The Toronto Platelet Immunobiology Group, Keenan Research Centre, Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Toronto, Ontario, Canada 4 Department of Medicine, University of Toronto, Toronto, Ontario, Canada 5 Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada 6 Research and Development, Canadian Blood Services, Toronto, Ontario, Canada
Key words alloimmunization; human leukocyte antigens; immunity; platelet refractoriness Correspondence Dr Katerina Pavenski St. Michael’s Hospital 30 Bond Street Toronto, Ontario M5B 1W8 Canada Tel: +1 416 864 5058 Fax: +1 416 864 3060 e-mail:
[email protected] doi: 10.1111/j.1399-0039.2012.01852.x
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.
Platelet alloimmunization and refractoriness
In 1910, for the first time, whole blood was transfused with intention to raise platelet count (1). By the 1950s, technology advancements allowed for the routine preparation of platelet concentrates from donated whole blood and platelet transfusion therapy became mainstream (1). Shortly thereafter, refractoriness was recognized as relatively common complication of chronic platelet transfusion support and the quest to identify the mechanisms responsible began. Platelets express a number of antigens that have been shown to influence post-transfusion counts and platelet survival; these include ABO, HLA Class I (A and B) and HPA (2). Platelet refractoriness refers to a lack of adequate post-transfusion platelet count increment and can be calculated based on the © 2012 John Wiley & Sons A/S Tissue Antigens, 2012, 79, 237–245
formulae that incorporate pre- and post-transfusion platelet counts, number of transfused platelets, and the patient’s size (3) (Table 1). A more recent definition elaborates that low post-transfusion corrected count increments (CCI) or percent platelet recovery (PPR) must be documented following at least two transfusions of fresh, random donor ABOcompatible platelets (3), as both the age of the platelet product and ABO compatibility have been shown to affect posttransfusion platelet counts (4). Platelet refractoriness is associated with a number of adverse outcomes including longer hospital stays (5), higher inpatient hospital costs (5), inferior survival (6), and more bleeding, including fatal bleeding (7). Both immune and non-immune causes have been shown to contribute to the development of platelet refractoriness. 237
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HLA alloimmunization in platelet transfusion
Table 1 Definitions of platelet refractoriness Measure of transfusion outcome Absolute count increment (ACI)
Formula
Values suggestive of refractoriness
Corrected count increment (CCI)
(post-transfusion platelet count)-(pre-transfusion platelet count) (ACI × BSA)/(number of platelets transfused)
Percent platelet recovery (PPR)
(100%) (ACI × TBV)/(number of platelets transfused)
At 60 min, ACI
