Platelet storage and transfusions: New concerns associated with an old therapy

Department of Microbiology and Immunology, University of Rochester.
Drug Discovery Today Disease Mechanisms 06/2011; 8(1-2):e9-e14. DOI: 10.1016/j.ddmec.2011.06.001
Source: PubMed


Platelet transfusion has long been practiced with rudimentary knowledge about optimal storage conditions and their implications for efficacy and, particularly, safety. Recent concerns about complications such as inflammation, thrombosis and altered recipient immunity have been raised about platelet transfusion. This review will discuss recent important findings that have raised these issues about platelet transfusion associated morbidity, mortality and the possible role of platelet storage in these associations.

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Available from: Neil Blumberg, Dec 16, 2013
    • "While this study has not specifically analyzed the biological mediators in the PC - SN , the PLT storage lesion has previously been well characterized . Ex vivo storage of PCs is associated with sig - nificant increases in levels of histamine ( Konca and others 2006 ) , sCD40L ( Kaufman and others 2007 ) , P - selectin , RANTES , PF4 , TGF - b , and IL - 8 ( Slichter and others 2005 ; Sahler and others 2011 ) . Histamine has been reported to regulate the expression and secretion of cytokines and chemokines during LPS - driven maturation of DCs by downregulating IL - 12 , IL - 6 , IP - 10 , MIP - 3a , IL - 18 , and RANTES , while increasing levels of IL - 8 and IL - 10 ( Mazzoni and others 2001 ) . "
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    ABSTRACT: The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.
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    ABSTRACT: Platelet component (PC) transfusion leads occasionally to inflammatory hazards. Certain BRMs that are secreted by the platelets themselves during storage may have some responsibility. First, we identified non-stochastic arrangements of platelet-secreted BRMs in platelet components that led to acute transfusion reactions (ATRs). These data provide formal clinical evidence that platelets generate secretion profiles under both sterile activation and pathological conditions. We next aimed to predict the risk of hazardous outcomes by establishing statistical models based on the associations of BRMs within the incriminated platelet components and using decision trees. We investigated a large (n = 65) series of ATRs after platelet component transfusions reported through a very homogenous system at one university hospital. Herein, we used a combination of clinical observations, ex vivo and in vitro investigations, and mathematical modeling systems. We calculated the statistical association of a large variety (n = 17) of cytokines, chemokines, and physiologically likely factors with acute inflammatory potential in patients presenting with severe hazards. We then generated an accident prediction model that proved to be dependent on the level (amount) of a given cytokine-like platelet product within the indicated component, e.g., soluble CD40-ligand (>289.5 pg/109 platelets), or the presence of another secreted factor (IL-13, >0). We further modeled the risk of the patient presenting either a febrile non-hemolytic transfusion reaction or an atypical allergic transfusion reaction, depending on the amount of the chemokine MIP-1α (<20.4 or >20.4 pg/109 platelets, respectively). This allows the modeling of a policy of risk prevention for severe inflammatory outcomes in PC transfusion.
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