Pathogen inactivation in platelet concentrate storage : effects on quality and utilization

Abstract

In transfusion medicine and blood banking, product quality and safety of patients are both essential. Blood transfusion is, in many instances, a lifesaving procedure; however, is not without risk. Blood products contain biological response modifiers (BRMs) that can induce febrile and allergic reactions and there is risk of donor/patient incompatibility, resulting in hemolytic transfusion reaction. Pathogen contamination of donor origin or due to collection and processing is another risk. The implementation of efficient viral screening has made blood transfusions safer, despite not addressing the risks from emerging pathogens or from bacterial contamination. For platelet concentrates (PCs) in particular, the standard storge conditions (room temperature) present an elevated risk of bacterial contamination and transfusion transmitted bacterial infection (TTBI) compared to other blood components, which are stored at subzero or refrigerated temperatures. Though the risk of TTBI can be minimized via the use of various screening assays, TTBI resulting in sepsis still occurs, with a high mortality rate. Therefore, methods have been developed to inactivate pathogens in blood products; such methods include photo or photochemical techniques, which influence the nucleic acids of pathogens and disable transcription. These methods have proven highly efficient in reducing the pathogenic load in blood products, namely PCs and plasma. As these methods have been approved through clinical trials and then implemented in routine use, indications of negative effects on blood products have emerged, specifically effects on platelet quality have been of concern. In response to the concern about reduced platelet quality, we investigated effect of pathogen inactivation (PI) with amotosalen and ultraviolet A (UVA) on the quality of stored platelets using a pool and split strategy and whole blood collected buffy coat (BC) platelet concentrates, with the aim of adding to the existing information. Multiple reports have suggested that micro RNA (miRNA) are important post transcription regulators in platelets, and there have been indications of altered miRNA profile due to pathogen inactivation (PI) methods. Therefore, we examined PI effects on 25 pre-selected miRNAs. Minimal influence was observed, with only 1 out of the 25 showing PI treatment-related down regulation. The release of BRMs from platelets into the storage media presents a potential risk of adverse events, as well as BRMs being indicators of platelet activation during storge. Monitoring the concentration of 36 proteins, we observed both reduction and increase of BRMs related to PI treatment. Additionally, PC utilization in national blood transfusion services (at the Blood Bank of Iceland) was analyzed pre- and post-PI implementation. We observed several PI treatment-related effects on both miRNA profiles and protein concentrations in the storage media, as well as elevated expression of markers of platelets storge lesion (PSL), though these effects did not translate to increased utilization or adverse events. We also observed increased product availability and more efficient stock management due to increased storge time, without an increase in outdated stock.

Í blóðbankastarfsemi og við blóðinngjöf skipta gæði afurðar og öryggi sjúklings öllu máli. Í mörgum tilfellum er blóðinngjöf lífsbjargandi meðferð, en ekki laus við áhættu. Blóð inniheldur lífvirka þætti sem geta stuðlað að aukaverkunum eins og hækkun á líkamshita og ofnæmi, að auki er áhætta á blóðgjafa og blóðþega misræmi sem getur valdið niðurbroti á blóðfrumum. Sýking í blóðhluta sem getur átt uppruna frá blóðgjafa eða við vinnslu á blóðhlutanum er annar áhættuþáttur. Innleiðing veiru skimunar í blóðhlutum hefur aukið mikið á öryggi við blóðinngjöf, án þess þó koma í veg fyrir sýkingar vegna óþekktra sýkla eða bakteríu smits. Almennt er blóðflögu þykkni (BÞ) geymt á vöggu og við stofuhita sem eru kjöraðstæður fyrir vöxt baktería, og þess vegna er áhætta á slíku smiti margföld í tilfelli BÞ borið saman við aðra blóðhluta sem eru kældir eða frystir við geymslu. Hægt er að lágmarka áhættu á bakteríu mengun með margvíslegum skimunar aðferðum, en þrátt fyrir slíkar aðferðir eru tilfelli þar sem bakteríu mengað BÞ veldur alvarlegri blóðsýkingu með hárri tíðni dauðsfalla. Til að draga enn frekar úr og jafnvel koma alveg í veg fyrir bakteríu mengun i BÞ hafa verið þróaðar smit-hreinsunar (SH) aðferðir sem byggja ljósa eða ljósa og efnatækni sem hafa áhrif á kjarnsýrur í sýklum og koma í veg fyrir umritun. Þessar aðferðir hafa sannað sig í að draga úr magni sýkla í blóðhlutum, þá sérstaklega BÞ og blóðvökva. Á sama tíma og þessar aðferðir fengu samþykki byggt á klínískum tilraunum og voru innleiddar inn i almenna blóðbanka starfsemi, komu fram vísbendingar um neikvæð áhrif á gæði blóðhluta sérstaklega BÞ.