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Cold storage conditions modify microRNA expressions for platelet transfusion.

ABSTRACT: MicroRNAs (miRNAs) are small RNA molecules that modulate gene and protein expression in hematopoiesis. Platelets are known to contain a fully functional miRNA machinery. While platelets used for transfusion are normally stored at room temperature, recent evidence suggests more favorable effects under a cold-storage condition, including higher adhesion and aggregation properties. Thus, we sought to determine whether functional differences in platelets are associated with the differential profiling of platelet miRNA expressions. To obtain the miRNA expression profile, next-generation sequencing was performed on human platelets obtained from 10 healthy subjects. The miRNAs were quantified after being stored in three different conditions: 1) baseline (before storage), 2) stored at 22°C with agitation for 72 h, and 3) stored at 4°C for 72 h. Following the identification of miRNAs by sequencing, the results were validated at the level of mature miRNAs from 18 healthy subjects, by using quantitative polymerase chain reaction (qPCR). Differential expression was observed for 125 miRNAs that were stored at 4°C and 9 miRNAs stored at 22°C as compared to the baseline. The validation study by qPCR confirmed that storage at 4°C increased the expression levels (fold change 95% CI) of mir-20a-5p (1.87, p<0.0001), mir-10a-3p (1.88, p<0.0001), mir-16-2-3p (1.54, p<0.01), and mir-223-5p (1.38, p<0.05), compared with those of the samples stored at 22°C. These results show that miRNAs correlate with platelet quality under specific storage conditions. The data indicate that miRNAs could be potentially used as biomarkers of platelet quality.

SUBMITTER: Mukai N

PROVIDER: S-EPMC6608970 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:BACKGROUND:Platelets (PLTs) are usually stored for up to 5 days prior to transfusion, although in some blood services the storage period is extended to 7 days. During storage, changes occur in both PLT and storage medium, which may lead to PLT activation and dysfunction. The clinical significance of these changes remains uncertain. METHODS:We performed a systematic review to assess the association between PLT storage time and clinical or transfusion outcomes in patients receiving allogeneic PLT transfusion. We searched studies published in English between January 2000 and July 2017 identified from MEDLINE, Embase, PubMed and the Cochrane Libraries. RESULTS:Of the 18 studies identified, five included 4719 critically ill patients (trauma, post-cardiac surgery and a heterogeneous population of critically ill patients) and 13 included 8569 haematology patients. The five studies in critically ill patients were retrospective and did not find any association between PLT storage time when PLTs were stored for up to 5 days and mortality. There was also no association between older PLTs and sepsis in the two largest studies (n?=?4008 patients). Of the 13 studies in haematology patients, seven analysed prolonged storage time up to 6.5 or 7 days. Administration of fresh PLTs (less than 2 or 3 days) was associated with a significant increase in corrected count increment (CCI) compared to older PLTs in seven of the eight studies analysing this outcome. One single centre retrospective study found an increase in bleeding events in patients receiving older PLTs. CONCLUSIONS:PLT storage time does not appear to be associated with clinical outcomes, including bleeding, sepsis or mortality, in critically ill patients or haematology patients. The freshest PLTs (less than 3 days) were associated with a better CCI, although there was no impact on bleeding events, questioning the clinical significance of this association. However, there is an absence of evidence to draw definitive conclusions, especially in critically ill patients.

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Cold storage conditions modify microRNA expressions for platelet transfusion.

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