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The effect of platelet storage temperature on haemostatic, immune, and endothelial function: potential for personalised medicine.

ABSTRACT: Reports from both adult and paediatric populations indicate that approximately two-thirds of platelet transfusions are used prophylactically to prevent bleeding, while the remaining one-third are used therapeutically to manage active bleeding. These two indications, prophylactic and therapeutic, serve two very distinct purposes and therefore will have two different functional requirements. In addition, disease aetiology in a given patient may require platelets with different functional characteristics. These characteristics can be derived from the various manufacturing methods used in platelet product production, including collection methods, processing methods, and storage options. The iterative combinations of manufacturing methods can result in a number of unique platelet products with different efficacy and safety profiles, which could potentially be used to benefit patient populations by meeting diverse clinical needs. In particular, cold storage of platelet products causes many biochemical and functional changes, of which the most notable characterised to date include increased haemostatic activity and altered expression of molecules inherent to platelet:leucocyte interactions. The in vivo consequences, both short- and long-term, of these molecular and cellular cold-storage-induced changes have yet to be clearly defined. Elucidation of these mechanisms would potentially reveal unique biologies that could be harnessed to provide more targeted therapies. To this end, in this new era of personalised medicine, perhaps there is an opportunity to provide individual patients with platelet products that are tailored to their clinical condition and the specific indication for transfusion.

SUBMITTER: Shea SM

PROVIDER: S-EPMC6683864 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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The effect of platelet storage temperature on haemostatic, immune, and endothelial function: potential for personalised medicine.

Shea Susan M SM Thomas Kimberly A KA Spinella Philip C PC

Blood transfusion = Trasfusione del sangue 20190701 4

Reports from both adult and paediatric populations indicate that approximately two-thirds of platelet transfusions are used prophylactically to prevent bleeding, while the remaining one-third are used therapeutically to manage active bleeding. These two indications, prophylactic and therapeutic, serve two very distinct purposes and therefore will have two different functional requirements. In addition, disease aetiology in a given patient may require platelets with different functional character ...[more]

PMID: 31385802

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Project description:Platelet transfusion can elicit alloimmune responses leading to alloantibody formation against donor-specific polymorphic residues, ultimately resulting in platelet transfusion refractoriness. Universal leukoreduction significantly reduced the frequency of alloimmunization after platelet transfusion, thereby showing the importance of white blood cells (WBCs) in inducing this alloresponse. It is, however, unknown if the residual risk for alloimmunization is caused by WBCs remaining after leukoreduction or if alloimmunization can be induced by platelets themselves. This study investigated the capacity of platelets to induce alloimmunization and identified potential product-related risk factors for alloimmunization. First, internalization of allogeneic platelets by dendritic cells (DCs) was demonstrated by confocal microscopy. Second, after internalization, presentation of platelet-derived peptides was shown by mass spectrometry analysis of human leukocytes antigen (HLA)-DR eluted peptides. Third, platelet-loaded DCs induced platelet-specific CD4 T cell responses. Altogether, this indicates a platelet-specific ability to induce alloimmunization. Therefore, factors enhancing platelet internalization may be identified as risk factor for alloimmunization by platelet concentrates. To investigate if storage of platelets is such a risk factor, internalization of stored platelets was compared with fresh platelets and showed enhanced internalization of stored platelets. Storage-induced apoptosis and accompanied phosphatidylserine exposure seemed to be instrumental for this. Indeed, DCs pre-incubated with apoptotic platelets induced the strongest IFN-γ production by CD4 T cells compared with pre-incubation with untreated or activated platelets. In conclusion, this study shows the capacity of platelets to induce platelet-specific alloimmune responses. Furthermore, storage-induced apoptosis of platelets is identified as potential risk factor for alloimmunization after platelet transfusions.

Dataset Information

The effect of platelet storage temperature on haemostatic, immune, and endothelial function: potential for personalised medicine.

Publications

The effect of platelet storage temperature on haemostatic, immune, and endothelial function: potential for personalised medicine.

Similar Datasets

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