Blood Product Manufacturing and Quality Assessment
A major experimental focus in our laboratory is in the area of platelet and red blood cell concentrates. In particular, we have developed extensive expertise in basic platelet biology and biochemistry, and are applying this knowledge to improve transfusion practice.
A better understanding of the effect of manufacturing procedures, donor characteristics and other factors on the quality of blood products will lead to improvements in product quality and ultimately patient care.
Despite their small size and lack of a nucleus, the biochemistry of platelets is surprisingly complex and nuanced. Through the application of leading edge technology, such as proteomics, we study the impact of storage on platelet concentrate quality. We have investigated the biochemical signaling pathways involved in the development of the platelet storage lesion, and developed potential interventions to reduce the deterioration of platelet quality during storage. We are interested in platelet apoptosis as it relates to stored platelets and in newly-discovered functions of platelets – particularly their ability to translate proteins. Our research findings provide evidence-based data on which new methods may be developed to improve platelet quality to benefit transfused patients.
In the area of red blood cells (RBC), we have recently examined how the timing of irradiation of RBC units affects the amount of cellular damage. Our findings suggested that storage times for irradiated RBC may need to be revised depending on clinical impact.
Our research also includes a significant component of applied development work with projects investigating issues arising in the manufacture of blood products. These studies range from determining the effect of modification of production processes and/or quality enhancements on Canadian Blood Services’ products to the investigation of the significance of donor characteristics on the final blood product.
Serrano K, Levin E, Chen D, Hansen A, Turner TR, Kurach J, Reidel A, Boecker WF, Acker JP, Devine DV: An investigation of red blood cell concentrate quality during storage in paediatric-sized polyvinylchloride bags plasticized with alternatives to di-2-ethylhexyl phthalate (DEHP). Vox Sang 2016; doi: 10.1111/vox.12355. [Epub ahead of print]
Johnson L, Schubert P, Tan S, Devine DV, Marks DC: Extended storage and glucose exhaustion are associated with apoptotic changes in platelets stored in additive solution. Transfusion 2015; doi: 10.1111/trf.13345. [Epub ahead of print].
Serrano K, Chen D, Hansen AL, Levin E, Turner TR, Kurach JDR, Acker JP, Devine DV: The effect of timing of gamma-irradiation on hemolysis and potassium release in leukoreduced red cell concentrates stored in SAGM. Vox Sang 2014; 106:379-381.
Prudova A, Serrano K, Eckhard U, Fortelny N, Devine DV, Overall CM: TAILS N-terminomics of human platelets reveals pervasive metalloproteinase-dependent proteolytic processing in storage. Blood 2014; 124:e49-60.
Levin E, Jenkins C, Culibrk B, Gyöngyössy‐Issa MIC, Serrano K, Devine DV: Development of a quality monitoring program for platelet components: a report of the first four years' experience at Canadian Blood Services. Transfusion 2012; 52:810-818.
Pathogen Reduction Technologies
Significant improvements over recent decades have reduced the risk of bacterial or viral contamination of blood products to very low levels. However, emerging pathogens and the detection limitations of systems to test for bacterial or viral contamination of blood products still pose a threat to our blood system. Our group is particularly interested in pathogen reduction technologies which have been developed to address these challenges.
Pathogen reduction technologies (PRT) hold great promise for improving the safety of blood transfusions; however, currently increased safety comes with a tradeoff with product quality. Our research will provide information about the effects of PRT treatment to inform further development of strategies to minimize the impact of PRT on product quality.
Pathogen reduction technologies (PRT) target the DNA and RNA of bacteria and viruses, damaging and inactivating them without targeting platelets or red blood cells. Our laboratory is investigating the effect of treatment with PRT on blood components, particularly platelet concentrates. Applying proteomic profiling, we are identifying the critical changes in the treated platelet concentrates. Our research has shown that pathogen reduction treatment increases markers of activation in platelet concentrates, which increase during the storage period.
Chen Z, Schubert P, Culibrk B, Devine DV: p38MAPK is involved in apoptosis development in apheresis platelet concentrates after riboflavin and ultraviolet light treatment. Transfusion 2015; 55:848-857
Schubert P, Culibrk B, Karwal S, Serrano K, Levin E, Bu D, Bhakta V, Sheffield WP, Goodrich RP, Devine DV: Whole blood treated with riboflavin and ultraviolet light: quality assessment of all blood components produced by the buffy coat method. Transfusion 2015; 55:815-823
Prudent M, D'Alessandro A, Cazenave JP, Devine DV, Gachet C, Greinacher A, Lion N, Schubert P, Steil L, Thiele T, Tissot JD, Völker U, Zolla L: Proteome changes in platelets after pathogen inactivation--an interlaboratory consensus. Transfus Med Rev. 2014; 28:72-83.
Schubert P, Coupland D, Culibrk B, Goodrich RP, Devine DV: Riboflavin and ultraviolet light treatment of platelets triggers p38MAPK signaling: inhibition significantly improves in vitro platelet quality after pathogen reduction treatment. Transfusion 2013; 53:3164-3173.
Schubert P, Culibrk B, Coupland D, Scammell K, Gyongyossy‐Issa M, Devine DV Riboflavin and ultraviolet light treatment potentiates vasodilator‐stimulated phosphoprotein Ser‐239 phosphorylation in platelet concentrates during storage. Transfusion 2012; 52:397-408.