Centre for Innovation Progress Report 2015-2016 July 5, 2016 Table of contents Executive Summary 2 Overview of the Centre for Innovation 3 Our research and education network 3 Our activities 3 Research and development progress 3 Safety and sufficiency of the blood supply 4 Blood products: Red blood cells 7 Blood products: Platelets 11 Blood products: Plasma, plasma products, and plasma product replacement 13 Hematopoietic stem cells 16 Organ and tissue donation and transplantation 18 Building capacity in transfusion and transplantation science and medicine 18 Salary support 18 Courses and diplomas 20 Education events 21 Education materials 23 Science communication 24 Leveraging expertise through collaborations 24 Clinical guidelines and leading practices 24 Blood operations 25 Blood safety 25 Research services 26 Governance 26 References cited 27 Appendix I: Funded projects i Appendix II: Publications viii Appendix III: Health Canada Financial Contribution xxx 1 Executive Summary The Centre for Innovation is Canadian Blood Services’ nucleus of research, development, and education. Through its multi-faceted activities, the Centre aims to advance Canadian Blood Services’ innovation agenda by fostering and supporting relevant discovery and applied research, facilitating dissemination and application of the created knowledge, preparing the next generation of scientific and health care experts in transfusion and transplantation medicine, and engaging with an interdisciplinary network of partners in Canada and beyond. By promoting the creation and translation of knowledge into new and enhanced practices, services, and technologies, the activities of the Centre for Innovation contribute to the advancement of transfusion and transplantation medicine in Canada and benefit Canadian patients and the health-care system • • • • • • • • • • The Centre for Innovation achievement highlights for 2015–2016 include: 317 peer-reviewed publications, including articles in high-impact journals such as Nature Communications, Blood, Lancet Hematology, Journal of Clinical Investigation, and Journal of Immunology. The average H-index of 26 of the Centre’s core investigators reflects their productivity and citation impact, and has increased from 2014-2015 highlighting a successful year for the Centre for Innovation. 23 technical reports shared within Canadian Blood Services and with partners. Subject-matter expertise and data included in these reports informed product and process improvements. 48 professionals formally trained through its national training program. Over 150 oral and poster presentations at national and international conferences. Over 70 major education events organized or supported, attracting an estimated 7,700 professionals. These included the Canadian Blood Services Annual International Symposium, the 10th Annual Transfusion Medicine Education videoconference in partnership with Ontario Regional Blood Coordinating Network, and the expansion of the Transfusion Medicine Camp in partnership with Drs. Callum and Lin. Rapid development of evidence-based donor deferrals in response to the Zika outbreak in South and Central America and the Caribbean to ensure the continuing safety of the Canadian blood supply. Two Health Canada license amendments supported to achieve process improvements while maintaining safety and quality: Approval for a new skin disinfection method for donors who have sensitivity to the primary chlorhexidine-containing disinfection method. An extension of the acceptable post-thaw storage period of cryosupernatant plasma from 24 hours to five days. The launch of two science communication initiatives in collaboration with Canadian Blood Services Public Affairs: a monthly Research and Education Round Up newsletter and RED – our research, education, and discovery blog. Publication of systematic reviews and clinical guidelines to influence clinical practice. In 2015-2016, this included development of recommendations for two clinical practice guidelines and updates to four chapters in the Clinical Guide to Transfusion. Significant milestones were reached in research partnerships with McMaster University and The Ottawa Hospital to link large databases and apply a “big-data” approach to investigate the impact of donor and product characteristics on transfusion recipient outcomes. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 2 Overview of the Centre for Innovation Through the Centre for Innovation, Canadian Blood Services conducts and facilitates research and education activities in transfusion and transplantation science and medicine. This report outlines the progress of the Centre during 2015-2016 and highlights key achievements that relate to the Centre’s goal of contributing to the safety, quality, and supply of blood components and related biologics. These successes were made possible by the continued funding to the Centre for Innovation from Health Canada, the provincial and territorial ministries of health, and our partners. The blood donors who make our research possible are also gratefully acknowledged. Our research and education network Instrumental to the Centre for Innovation’s research expertise are 11 principal investigators (bolded names throughout the report): seven who lead discovery research laboratories and four who conduct targeted research around product and process development. Employees of Canadian Blood Services, these investigators are integrated with the organization to effectively respond to its research needs. These investigators are also cross-appointed to Canadian academic institutions, allowing for the leveraging of resources and expertise available through those institutions. Complementing this core research group, the Centre for Innovation engages 29 Canadian Blood Services medical experts and epidemiologists (bolded names throughout the report). This group provides medical expertise, contributes to medical research initiatives and, along with the 11 principal investigators, addresses the education needs of the organization and of the transfusion and transplantation system. Over the last year, Canadian Blood Services’ research and education internal network was strengthened by contributions from 27 external investigators. These investigators are Canadian academic researchers leading research projects funded through the Centre’s competitive research and training programs. The Centre’s network is also strengthened nationally and internationally through partnerships with industry, blood operators around the world, academia, and not-for-profit organizations and associations, 38 of which were formalized during the year. Our activities In 2015-16, the Centre’s competitive funding programs initiated or continued funding of 55 research projects, 49 trainee awards, and three Program Support Awards. The product and process development group worked on 54 targeted research projects in support of Canadian Blood Services’ supply chain or with industry partners (see Appendix 1 for a list of all projects). The Centre also organized or supported 72 educational events and programs. Finally, a research, education and discovery (R.E.D.) blog and a monthly e-newsletter were launched to further disseminate the outcomes of those activities. Internationally, the Centre continued its leadership role in the development of clinical guidelines through the activities of the International Collaborative for Transfusion Medicine Guidelines and in evidencebased decision making by further developing and facilitating the use of a Risk-Based Decision-Making Framework for Blood Safety. The Centre for Innovation staff administer these programs while leveraging Canadian Blood Services’ financial, legal, information technology, communication, and human resources services. Research and development progress Canadian Blood Services has continued to undertake and facilitate targeted research and development to ensure that Canada’s healthcare system is well positioned to address emerging medical and scientific trends in transfusion and transplantation, risks, opportunities, and technologies, and to lead change for the benefit of patients and donors. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 3 Safety and sufficiency of the blood supply Donors and donations Mandatory reading for all donors, the pre-donation reading material provides information on possible complications of donation and the risks of transmissible disease to transfusion practice. Drs. Sheila O’Brien and Mindy Goldman studied donor attention to this reading material, which relates to health of donors and the safety of donations and may therefore impact the sufficiency and safety of the blood supply.1 Overall, the study suggests that pre-donation reading material may not be an effective education tool, particularly for repeat donors. While first-time donors were relatively attentive, the study revealed a low motivation to read the material, particularly in repeat donors. Donors are reluctant to read any more than they deem necessary, a decision based on how they perceive the relevance or importance of the information. Poor literacy may also play a role in the effectiveness of the material. These findings will guide our organization in developing more appropriate alternatives, including educational messages facilitated by technology, such as short messages attached to appointment reminders. Canadian Blood Services tests all blood donors for hemoglobin prior to donations to ensure the health of the donors. In June 2015, the DiaSpect machines used to measure donor hemoglobin became unavailable. A replacement, the CompoLab hemoglobinometer, was assessed by Dr. Jason Acker and found to meet the analytical and ease-of-use requirements of the organization. However, when the old and new systems were compared, the results indicated a significant difference in analytical performance when measuring identical samples, suggesting that the number of donors deferred because of a low hemoglobin measurement (<125 g/L) would change once the new system was implemented.2, 3 Dr. John Blake conducted a study to estimate the projected change to donor deferrals and concluded that the new CompoLab hemoglobinometer would result in an increase in the proportion of individuals deferred from donating blood,4 affecting the sufficiency of the blood supply. A trial of the new hemoglobinometers was instituted and conducted by Dr. Goldman, including an algorithm permitting staff to retest hemoglobin in donors failing the initial fingerstick test. If the donor is in agreement, a second fingerstick sample is obtained and measured twice. If both repeat measurements are over the cutoff threshold, the donor is accepted. The trial results, analyzed by our epidemiology group, demonstrated that with the new algorithm, donor hemoglobin deferral rates would be approximately equal to those with the DiaSpect machines. Deferral rates in the year post-implementation of the CompoLab machines using the new testing algorithm have been similar or slightly below what they were using DiaSpect. Careful evaluation prior to implementation permitted the organization to take appropriate steps to maintain the adequacy of the blood supply. Further work on reducing hemoglobin deferrals will require enhanced donor education about iron needs and reduced frequency of donation in female donors. On July 22, 2013, Canadian Blood Services changed the deferral period for men who have sex with men (MSM) from a permanent deferral to a five-year deferral. Drs. O’Brien, Goldman and colleagues examined data following this change.5, 6 The results showed no impact on safety, with unchanged HIV rates in donations in the two years of post-implementation monitoring. A donor survey revealed that although there was no change in the percentage of male donors with recent male partners, overall donor compliance improved, suggesting a potential positive impact on safety of the blood supply. Finally, the change led to a modest increase in the number of eligible MSM donors. Based on these encouraging data and information from other blood operators, a submission to Health Canada has been made to further decrease the MSM deferral to a one-year deferral. Blood-borne pathogens Horizon scanning is essential to maintain readiness for emerging infectious diseases in Canada and internationally. In 2015, the biggest concern for emerging infectious agents came from mosquito-borne pathogens, in particular Chikungunya, dengue virus, and, more recently, Zika virus. While the mosquitos that transmit these pathogens do not survive in Canada, they are found in many areas popular with Canadian travelers, including Mexico, the Caribbean, South America, and the southern United States. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 4 International travel is commonplace among Canadian Blood Services’ donors, as demonstrated by a recent survey conducted by Drs. O’Brien, Goldman, and colleagues in which more than half of donors reported travel abroad.7 The rapid spread of Zika in Mexico, Central and South America, and the Caribbean in 2015 required an equally rapid response from Canadian Blood Services to ensure the continued safety of the Canadian blood supply. Under the leadership of Canadian Blood Services chief medical and scientific officer Dr. Dana Devine, a risk assessment was conducted by Drs. Margaret Fearon, O’Brien, and Goldman in collaboration with Héma-Québec’s Drs. Gilles Delage and Marc Germain, to determine an appropriate travel deferral period for blood donors (Response to Zika Clarifax, 2016). A 21-day temporary travel deferral period was justified and found to offer an extremely wide margin of safety for the possible transmission of Zika following transfusion. The new temporary 21-day waiting period was implemented on Feb 5, 2016 and later officially approved by Health Canada. Learning about infectious threats to the blood system is the first step in knowing how to manage the risks, and Centre for Innovation investigators have made some critical discoveries on this front within the past year. Dengue is the most common arbovirus and a pathogen of concern to blood systems, particularly those in endemic regions. Transmitted through the bite of Aedes mosquitoes (like its close cousins West Nile virus and Zika virus), symptoms range from mild flu-like symptoms to, in rare cases, severe hemorrhagic fever, which can be fatal. The global burden of dengue virus is considerable: Approximately 2.5 billion people are at risk and almost 400 million people are infected every year, of whom about 25,000 die. Blood donor systems are vulnerable to dengue virus, and although it is mostly in tropical and subtropical regions, travel and increasing globalization means it remains an emerging infectious threat. In 2015, research by Dr. Ed Pryzdial advanced the fundamental understanding Blood platelets do not have a nucleus, the part of the of how dengue virus replicates. The cell where genetic material and much of the researchers showed that the dengue virus genome is replicated and dengue viral machinery to replicate that material is found. So in proteins are synthesized by blood the past, platelets have not really been considered a platelets.8 Further research revealed that cell in which viruses could replicate. In recent years even at low levels of virus that mimic an it’s been discovered that platelets can do part of the asymptomatic donor, infectious dengue job. They can convert RNA to protein. Now in this virus persists and its genome can study, we show for the first time that dengue virus replicate in platelet and red blood cell enters platelets and uses this machinery to replicate 9 units stored under standard conditions. its RNA-based genome and to synthesize viral Knowing that the virus can survive and proteins to begin its life-cycle. replicate in fresh blood components helps all blood operators to better Dr. Ed Pryzdial understand the risks posed by dengue, and it helps Canadian Blood Services choose appropriate donor deferrals for travel to regions in which dengue and other viral risks are endemic.10 Ebola is another emerging pathogen that continued making the headlines in 2015. The devastating Ebola outbreak in Liberia, Sierra Leone and Guinea resulted in over 28,000 cases and more than 11,000 deaths. With limited spread outside of west Africa, and Health Canada-approved deferral criteria in place at Canadian Blood Services for donors who may have been exposed to Ebola, the safety risk to the Canadian blood supply is relatively low.11 Canadian Blood Services has developed a Health Canada-approved protocol for the collection of convalescent plasma to treat patients with Ebola in Canada, if that were to occur. This protocol can also be utilized in other emerging infections where convalescent plasma has been shown to be efficacious. However, the effectiveness of convalescent plasma for Ebola remains unclear, and Ebola continues to be a public health concern of international importance with no approved and proven vaccines or treatments in sight. Using a mini-genome model system that generates Ebola virusCanadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 5 like particles to infect cells, Dr. Don Branch with colleagues from the University of Toronto and collaborators from the National Institutes of Health (NIH), Biogen, and the National Microbiology Laboratory in Winnipeg screened a panel of candidate drugs for antiviral activity.12 They compared the activities of eight different antivirals, including drugs repurposed for the treatment of Ebola: type I interferons (IFNs) and nucleoside analogs. The data indicate that IFN-ß is a potent inhibitor of Ebola virus, contributing to the decision to conduct a clinical trial of IFN-ß treatment for Ebola virus disease in Guinea.13 Importantly, some drug combinations inhibit Ebola replication when administered 24 hours post-infection, a finding that has implications for clinical use, since lower doses potentially decrease sideeffects and reduce the likelihood for the emergence of drug resistance. These studies set the stage for both preclinical and clinical evaluations of potential Ebola treatments. While the threat of Ebola to the Canadian blood system is extremely low, development of effective affordable treatment options will play a role in containing future outbreaks of this devastating disease. In a different approach involving collaborators from Serbia, The Netherlands and the United States, Dr. Branch applied in silico methods, focusing on approved and experimental drugs with the aim of identifying inhibitors of Ebola virus infection.14 Applying well-established criteria, ibuprofen was selected as the best candidate for Ebola virus disease treatment and a mechanism of action was proposed. The findings suggest further investigation of ibuprofen and ibuprofen-inspired drugs as inexpensive, lowtoxicity, and widely accessible candidates for use in the treatment of Ebola should be considered. One approach that could mitigate pathogenic risks in blood components is pathogen inactivation. A research focus at Canadian Blood Services, there are numerous studies underway assessing its safety and effectiveness. Pathogen inactivation is a blood safety approach that is broad-spectrum, in that it destroys all viruses, parasites and bacteria (not prions) that may be present in a blood component. It is proactive in that it removes the need to develop specific assays to test for each pathogen of concern. In Dr. Devine’s laboratory and other Canadian Blood Services laboratories, investigations are under way examining many aspects of pathogen inactivation technologies, including their impact on blood components from a quality perspective, as well as studies to understand these effects at a cellular and molecular level. Pathogen inactivation was a major topic at a knowledge exchange event with Health Canada in November 2015 titled Blood Safety in Canada: Where are we today? In this event, Dr. Devine addressed an audience comprised mainly of members of Health Canada’s Health Products and Food Branch (HPFB), as well as some attendees from the Public Health Agency of Canada (PHAC) and the Canadian Institutes of Health Research (CIHR). Dr. Devine provided an overview of pathogen inactivation technologies used by blood operators around the world, presenting Canadian Blood Services’ research undertaken to inform development of this new technology. She discussed the system-level challenges in implementing pathogen inactivation in Canada. In Europe, both Mirasol and INTERCEPT pathogen inactivation technologies are approved, have been in use for over a decade, and have gained widespread acceptance and adoption. Currently in Canada, no pathogen inactivation technology is licensed; however, a clinical trial involving Canadian Blood Services is underway to investigate the Mirasol pathogen reduction system (TerumoBCT) in platelets (the PREPAReS trial). The Cerus INTERCEPT system, which was recently approved for use with platelets and plasma in the United States, is seeking licensure in Canada. Among other challenges, successful implementation of pathogen inactivation technologies in Canada will require stakeholder engagement and acceptance by physicians and transfusion recipients. To aid in policy development and implementation of strategies such as pathogen inactivation, Canadian Blood Services’ medical director Dr. Kathryn Webert and adjunct scientist Prof. Nancy Heddle were part of a study with colleagues from McMaster University to understand awareness of blood system practices in Canada and to assess opinions regarding pathogen inactivation and health risk perceptions among the Canadian public.15 The findings of this email-based survey showed low reported knowledge of pathogen inactivation among the Canadian public and mixed opinions: the majority of those surveyed agree with its use and yet many were hesitant about the addition of chemicals associated with pathogen Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 6 inactivation. Increasing public awareness about pathogen inactivation will be beneficial to the successful implementation and acceptance of this new (to Canada) approach to blood safety. Adverse transfusion reactions Adverse transfusion reactions can occur in a patient following transfusion of blood products. Understanding how and why those reactions occur can help to improve the safety of the blood supply. Transfusion-related acute lung injury (TRALI) presents as acute respiratory distress after a transfusion and is a leading cause of transfusion-related mortality. However, there is little understanding of the basic mechanisms of TRALI. As noted by Dr. Webert in an editorial in Transfusion, TRALI is a complex syndrome about which much remains to be known. Some of the confusion around TRALI may be because this is potentially multiple diseases with many causes, prognoses, and means of treatment or prevention.16 Canadian Blood Services in partnership with CIHR funds operating grants aimed at better understanding TRALI. Dr. John Semple, a Canadian Blood Services adjunct scientist from the Keenan Research Centre for Biomedical Science of St. Michael's Hospital in Toronto, has developed two mouse models to address the recipient factors that may play a role in the development of TRALI, based on the hypothesis that recipient cellular and soluble immune factors play a significant role in inducing and modulating TRALI reactions. Using these models, Dr. Semple and his group recently demonstrated that C-reactive protein, a marker of infection and inflammation, mediates antibody-dependent TRALI.17 This finding links TRALI and inflammation and lends support to the theory that systemic inflammation is a risk factor for the development of TRALI. Dr. Semple is continuing his investigations and is collaborating with Dr. Wolfgang Kuebler, also from St. Michael’s Hospital and the University of Toronto, and a recipient of Canadian Blood Services / CIHR funding to study the mechanisms of antibody-independent TRALI. Together, they have described and visualized alveolar dynamics in the acutely injured lung.18 Dr. Kuebler has developed a mouse model to study the effects of aged versus fresh platelets on lung injury and has identified a key role of lipid mediators named ceramides in inducing lung injury. Their findings are furthering the fundamental understanding of TRALI and will have implications for the safety of transfusion products. In another study relating to transfusion recipient safety, Dr. Goldman, in collaboration with Canadian Blood Services’ colleagues Drs. Debra Lane and Webert, along with Robert Fallis, assessed the prevalence of the K (also called Kell or KEL1) red blood cell antigen in Canadian prenatal patients.19, 20 Similar to the D antigen, K is important as K-negative women who develop anti-K antibodies can be at risk of hemolytic disease of the fetus and newborn (HDFN). In some jurisdictions, women of childbearing potential are transfused with K-compatible blood to reduce the risk of HDFN. To understand if this practice should be considered in Canada, the rate of anti-K antibodies in pregnant women and the likely cause (i.e. previous transfusion or previous pregnancy) was investigated. This study showed a history of transfusion is a risk factor for developing anti-K antibodies and suggests that providing Kmatched blood to prevent anti-K antibodies from developing in younger females may be an effective way to reduce the incidence of HDFN in Canada and other countries that have not yet adopted this practice. Blood products: Red blood cells With almost 760,000 units delivered to hospitals annually, red blood cells are the most common biologic Canadian Blood Services distributes. Red blood cells are produced from whole blood using one of two methods at Canadian Blood Services: the whole blood filtration method or the buffy coat method. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 7 Two unique research collaborations exploring red blood cell product characteristics and patient outcomes reached milestones this year. Prof. Nancy Heddle, a Canadian Blood Services adjunct scientist from McMaster University, and Dr. Dean Fergusson from The Ottawa Hospital collaborated with the Centre for Innovation to link hospital databases that included the outcomes of over 50,000 transfused patients with Canadian Blood Services’ data describing the almost 280,000 red cell products these patients received. The Ottawa Hospital database was also linked to the CIHI database. Both of these large retrospective studies were funded through the Canadian Blood Services / CIHR operating grant program and included Canadian Blood Services’ collaborators Drs. Acker, Webert and O’Brien. 21-24 In an impressive feat of big data mining, the researchers showed that the health outcomes of patients after transfusion are associated with blood donor age, donor sex, and the manufacturing method used to separate the red blood cells from whole blood. These studies are the first to demonstrate associations between patient outcome (mortality) and whole blood processing method, donor sex and age. Specifically, the McMaster study observed an association between in-hospital mortality and exposure to fresh (storage days 1-7) whole blood filtration-produced red cells, suggesting that this product may be associated with a greater risk of harm compared with red cells produced by the buffy coat method and stored for 8-35 days. Regarding donor sex, two associations with increased risk of in-hospital mortality were observed: females receiving male red blood cells, and males receiving red blood cells from females younger than 45 years of age,22 suggesting that clinical outcomes in transfused patients may be negatively impacted by donorrecipient sex discordance. Similarly, The Ottawa Hospital study observed an association between transfusion of red cells from female donors and increased risk of mortality. Transfusion of red blood cells from donors under 30 years of age was also associated with an increased risk of mortality.23 These Canadian studies are at the forefront of a new era in transfusion medicine, using a "big data" approach to permit in-depth interrogation of the factors impacting transfusion outcome. However, while the associations these studies revealed are intriguing, it is worth noting that as retrospective studies using secondary data, both studies were designed to generate hypotheses and do not demonstrate cause and effect. Before any changes to the blood system would be considered, these findings need to be independently verified in further studies. Additional analyses and follow-up studies are now underway. There are some parallels between the findings in the McMaster and The Ottawa Hospital studies regarding the age of blood and the recently published Age of Blood Evaluation (ABLE) multicenter randomized controlled trial in critically ill adults, which had hypothesized that fresh red cells stored for less than eight days would be superior to standard-issue red cells. However, the findings of ABLE showed transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90day mortality among critically ill adults.25 There are many potential reasons that ABLE and other randomized controlled trials did not see poorer outcomes with older blood as had been hypothesized. As discussed in a recent JAMA editorial penned by Dr. Acker with Dr. Philip Spinella from Washington University, the length of storage of the red blood cell products may not be the only critical variable that needs to be evaluated in future prospective randomized controlled trials; there are a number of donorspecific and product manufacturing-specific factors that influence product quality and these need to be considered and assessed.26 Understanding the relationship between manufacturing methods, donor factors and red blood cell quality and ultimately recipient outcomes will help blood operators to ensure the safety and efficacy of transfused products. This is an active area of research at the Centre for Innovation, facilitated by the extensive body of data Canadian Blood Services maintains on our products. As well as quality control data, a large part of our product knowledge comes through the Quality Monitoring Program (QMP), a unique program introduced in 2005 and led by Craig Jenkins as part of the product and process development group. To better understand quality parameters, a series of biological markers associated with each of our blood products was developed through the QMP. These markers go beyond regulatory requirements and now comprise over a decade’s worth of invaluable data on the products we produce, setting the stage for in-depth analysis of the factors that impact product quality. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 8 Much of the work to understand the factors that impact product quality is being led by Dr. Acker. For example, in a study completed in 2015, Canadian Blood Services’ quality control data were linked with manufacturing and donor records for 28,227 red cell concentrates. The results, published in Vox Sanguinis, showed that stored red blood cell characteristics are influenced by pre-storage processing and donor factors.27 Another recent study compared the two manufacturing processes used at Canadian Blood Services and assessed the concentration, size, and lipid composition of extracellular vesicles in the resulting red blood cell components. Differences were found depending on the manufacturing method, particularly in the cellular source of extracellular vesicles.28 Building on previous work showing that the manufacturing method used to produce red blood cell components affects in vitro measures of product quality, Dr. Acker collaborated with Dr. Sonia Bakkour and colleagues at Blood Systems Research Institute in San Francisco. By teaming up, the researchers were able to study red blood cell units manufactured using nine different processes.29 They looked at the levels of DAMPs or damage-activated molecular patterns, specifically microparticles and mitochondrial DNA (mtDNA) present in blood, which may indicate cellular damage. Both We think that our research could lead to finding ‘the microparticles and mtDNA are thought best’ way to manufacture red blood cells. It’s clear to lead to inflammation and may play a role in adverse reactions in transfusion now that manufacturing methods matter. We and our recipients. Across the nine respective research sponsors — Health Canada, US manufacturing methods, clear differences National Institutes for Health, Heart, Lung and Blood were observed in microparticle counts Institute are keen to explore what’s in the blood bag and mtDNA levels, suggesting that or in the filters or in the tubing, for example, that can different manufacturing processes cause be minimized or eliminated, improving the outcome in variable levels of damage to the red patients who receive blood transfusions. blood cells. Future work is planned to determine what aspect of the Dr. Jason Acker manufacturing process cause damage, and to investigate the impact of donor factors. Also in 2015, two studies looked at red blood cell quality for pediatric transfusions. In work conducted by Drs. Devine and Acker in collaboration with the global health care company Fresenius-Kabi, the quality of red blood cells in three different types of bags designed for pediatric transfusion was compared.30-32 Currently red blood cells in Canada and many other jurisdictions are stored in polyvinyl chloride bags plasticized with di-2-ethylhexyl phthalate (DEHP). However, there are public health concerns around the use of DEHP, particularly in neonatal and pediatric patients. Two alternative plasticizers were assessed, and the results indicated that a less toxic plasticizer called DINCH may represent a viable alternative to DEHP. The results of this research aids Fresenius-Kabi as they continue their development of bags with alternative plasticizers that will be safer for pediatric patients. Together with Dr. Robert Ben at the University of Ottawa, Dr. Acker has been experimenting with small molecule ice recrystallization inhibitors to improve the storage of frozen red blood cells.33, 34 Red blood cell freezing, or cryopreservation, is used to preserve units that have rare phenotypes as well as for autologous storage and military uses. Ice recrystallization during thawing and freezing, which causes cellular damage, is a major limitation of the cryopreservation process. Currently high glycerol concentrations (40% v/v) and slow freezing rates are used to limit the cellular damage, but these novel ice recrystallization inhibitors permit use of lower (15% v/v) levels of glycerol. These inhibitors have been shown to mitigate red blood cell lysis during freezing, transient warming and thawing, and have the potential to improve the post-thaw viability of frozen red blood cells. Use of these novel inhibitors could help improve the quality and efficacy of frozen red blood cell with rare phenotypes, a precious and limited resource for difficult-to-match patients in need of transfusion. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 9 In 2015, we saw the culmination of a broad-ranging multiyear “bench-to-bedside” study conducted in Dr. Acker’s laboratory, in partnership with Haemonetics, to investigate, implement, validate, and monitor a new red blood cell washing apparatus at Canadian Blood Services.35 With the introduction of any new process within our organization, the primary goal is to maintain patient safety. Implementing the ACP215 red cell washing system resulted in a blood product with a longer shelf-life that not only ensured patient safety but also improved blood product utilization. The new washing system has clear advantages over the old; most importantly, longer storage time after washing (from one day to one week), which has reduced the number of washed red blood cells that are discarded, limiting product wastage, saving money, and improving efficiency.36-38 It has made it easier for Canadian Blood Services to provide washed products to hospitals and for the hospitals to provide those washed products to the patients that need them. Since the new system was introduced, the use of washed red blood cells has increased at hospitals while, in a study published this year involving Canadian Blood Services’ medical director Dr. Barbara Hannach and colleagues, safety and transfusion efficacy were maintained.39 Interestingly, there was a small decrease in the number of units transfused per transfusion episode after implementation, reducing the exposure of recipients to blood products. Investigations into novel methods to assess red blood cells before transfusion also progressed in 2015. Dr. Devine, in collaboration with Drs. Robert Turner and Michael Blades at the University of British Columbia made advances on their efforts to apply Raman spectroscopy – a non-destructive testing method – to red blood cells.40, 41 An advantage of this approach is that it can be used on red blood cells in their storage bag without compromising the sterility of the units. It is being applied to determine storage and donor-related changes in red blood cells, and, although still at the proof-of-concept stage, the findings suggest there may be benefit in developing a Raman instrument for the rapid non-invasive assessment of blood-bag biochemistry. Canadian Blood Services’ Dr. Mark Scott, in collaboration with Dr. Hongshen Ma in a Canadian Blood Services / CIHR-funded project, have continued their developments into a microfluidics device that measures red blood cell deformability. This device measures deformability on a single cell level, requiring very small volumes, and, using this device, the researchers showed consistent degradation of red blood cell deformability over storage. The device was also able to show significant donor variability in red blood cell quality and storage capacity, indicating its promise as a method to individually assess the quality of stored red blood cell units.42 Managing the blood products necessary to ensure every patient has access to the right product at the right time is an everlasting cycle of supply and demand. Universal O-negative blood is in high demand, as it can be transfused in emergency situations when there is no time to test the patient’s blood type. For that reason, 12 per cent of hospital requests Canadian Blood Services receives are for O-negative blood; however, only about seven per cent of Canadians have this blood type. While Canadian Blood Services’ O-negative donor base is above the national average at 10 per cent, this donor group is consistently asked to donate every 56 days to keep up with hospital demand. This is difficult to sustain and results in an imbalance between the supply and demand for O-negative blood. ‘Making’ type O blood using other red blood cells could help reset the balance. This year, in a study partly funded by Canadian Blood Services / CIHR and led by Drs. Stephen Withers and Jay Kizhakkedathu, both from the University of British Columbia, the concept of universal blood was brought closer to reality.43, 44 The researchers improved a naturally occurring enzyme that can cleave A and B antigens away from the red blood cell surface in such a way that a much smaller amount of the enzyme is needed to cleave a much higher percentage of antigens. This brings us one step closer to a practical method for making a blood type that can be transfused into most people. Through its Canadian Blood Services / CIHR operating grants, Canadian Blood Services is funding some basic research that ultimately aims to reduce the use of blood products. Trauma or surgical procedures often require the use of large amounts of transfused blood products. Dr. Donald Brooks at the University of British Columbia has been working on polymer-induced hemostasis – an approach to reduce blood loss in these situations, and, consequently, reduce blood use. His laboratory has successfully developed two Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 10 types of adherent sealant polymers that arrest red blood cells by two different mechanisms. One approach uses choline phosphate groups on the surface of a pad that interacts with red blood cells and platelets and forms a strong adhesion. However, choline phosphate groups cannot yet be synthesized in the commercial quantities that would be needed to develop this approach. Therefore, an alternative polymer was developed that works by a different mechanism, binding red blood cells effectively and forming an aggregated web that will arrest all blood cells without engaging the clotting system.45 Currently, type-matched donor red blood cells are the only way to replace oxygen-carrying capacity. With funding from a Canadian Blood Services / CIHR grant, Dr. Ronald Kluger at the University of Toronto has been working on a safe and effective hemoglobin-based oxygen carrier that could be used to replace red blood cells in situations where transfusion products are unavailable or limited, such as in remote areas. Dr. Kluger’s work involves chemical transformation of hemoglobin, the oxygen-carrying protein in red blood cells, into an alternative oxygen carrier that can be given to patients in need. Clinical trials of first generation versions of stabilized hemoglobin revealed an unexpected side effect – an increase in blood pressure due to the hemoglobin reacting with nitric oxide. Dr. Kluger and his group are working to alter hemoglobin to form a cross-linked version that cannot react with nitric oxide, but that is stable, safe and still capable of oxygen transport.46 They have also successfully stabilized another red blood cell protein, superoxide dismutase, which removes potentially toxic free radicals and will be important to have in co-circulation with modified hemoglobin.47 Dr. Thomas Ming Swi Chang from McGill University has been developing a novel soluble nanobiotechnological complex that can carry out the major functions of red blood cells.48 This complex has been successfully freeze-dried, allowing it to be stored for extended time periods and to be pathogen inactivated, and the researchers are working to make this complex more commercially viable.49,50 Blood products: Platelets Platelets are small, anucleate cells that circulate at the periphery of the blood stream and play a key role in the formation of blood clots. Many conditions can lead to low platelet counts and require transfusion to manage the increased risk of bleeding. Canadian Blood Services supplies approximately 116,000 platelet doses a year. As platelets lose their ability to function when stored in the cold, they must be stored at room temperature with constant gentle agitation to allow for gas exchanges. This requirement increases the risk of bacterial growth if the unit is contaminated, leading to short storage times and inventory problems. While transfusion reactions due to contaminated platelets are rare, they remain a challenge for the industry as they can be fatal. Dr. Sandra Ramirez-Arcos leads the development research group that supports Canadian Blood Services in implementing appropriate processes to minimize bacterial contamination. Preventing bacterial contamination begins at the donor interview and health check, which screens for any donors who may be ill. Disinfection of the donor’s skin before donation is the next line of defense, together with diversion of the first portion of the blood draw. These are critical steps as bacteria that live harmlessly on the skin’s surface can cause serious reactions if transfused. However, while disinfection and diversion are effective they are not perfect, and the risk of bacterial contamination remains (estimated at about 0.01 per cent of platelet components).51 At Canadian Blood Services, the primary skin disinfection method is a one-step (two per cent chlorhexidine/70 per cent alcohol-containing) swabstick method. For the approximately three per cent of blood donations at Canadian Blood Services that report sensitivity to chlorhexidine, an alternative two-step method using a 70 per cent isopropyl alcohol scrub followed by an ampoule of two Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 11 per cent iodine tincture was used, but this was discontinued by the manufacturer in October 2015. Dr. Ramirez-Arcos together with Dr. Goldman assessed alternative disinfectants and another two-step (10 per cent povidone-iodine swabstick followed by isopropanol swabstick) method was found to be as efficient as the former primary skin disinfection method.52, 53 A Health Canada license amendment for this change was approved in 2015-2016, and this method replaces the discontinued product. Currently, all platelet components are screened for possible bacterial contamination in an automated culture-based system using samples drawn on day one and monitored throughout the platelets’ five-day storage period. Dr. Ramirez-Arcos investigated the pH SAFE system, a noninvasive method that allows for repeated measurement of the pH platelet components, as a rapid method to detect bacterial contamination in platelet components. Her group found that a significant decrease in pH could serve as an indicator of clinically significant levels of bacterial contamination; however, differences in pH decline were observed among bacterial species. It was concluded that this system would be best used for continuous pH monitoring in platelet components or as a point-of-care device.54 The quality of platelets declines during storage in a phenomenon called the “platelet storage lesion”. The mechanisms and effects of this storage lesion has long been an active area of research at Canadian Blood Services. In Canada, platelets are stored in plasma, but storing platelets in an additive solution may improve their long-term storage quality. In collaboration with the Australian Red Cross Blood Service, Dr. Devine explored the effect of storing platelets in an additive solution called SSP+ with a minimum (20 per cent) amount of carryover plasma for an extended storage period.55 Plasma is an important source of glucose for stored platelets and the results showed glucose exhaustion occurred between days seven and 10 of storage and was associated with pro-apoptotic changes in the platelets. The findings suggest extension of the platelet shelf-life beyond seven days is not possible when the platelets are stored in an additive solution lacking glucose and the unit has a low percentage of plasma carryover. In a study funded by a Canadian Blood Services / CIHR operating grant, Dr. Patrick Provost from Université Laval has been investigating platelet microRNAs during storage under blood bank conditions. Through this work, important novel insights into platelet microRNAs were gained, including how they regulate protein expression in platelets and in other cells and how they are affected by storage of platelet concentrates and by treatments such as pathogen inactivation. Despite lacking a nucleus, platelets contain messenger (m)RNA and can synthesize protein. MicroRNAs are known to mediate mRNA translational repression through proteins of the Argonaute (Ago) family. In 2015, the Provost group published a study showing that platelet activation is associated with removal of the mRNA repression of Ago2 and TIA-1 protein complexes through their rearrangement.56 Further, it was shown that thrombin-activated platelets release microparticles that contain functional protein-microRNA complexes and that can be internalized by other cells and impact their transcriptome. 57-59 The role of microRNAs and these microRNAcontaining microparticles in thrombosis and hemostasis remains unclear, as do the implications of these findings in transfusion medicine. However, as platelets may be activated and release microRNAcontaining microparticles during manufacturing or storage, this intriguing finding warrants further investigation. These in vitro studies have shown that pathogen inactivation may exacerbate platelet activation and decrease platelet microRNA and mRNA levels,60, 61 supporting the possible release of microRNA in microparticles in response to pathogen inactivation. This year, a protocol for the PREPAReS clinical trial exploring pathogen inactivation of platelets was published.62 Designed to assess the clinical effectiveness of standard versus pathogen-reduced buffy-coatderived platelet concentrates in plasma in hemato-oncological patients, PREPAReS involves centres in The Netherlands, Norway, and here in Canada, where one academic centre and four hospitals are participating. Under the leadership of Canadian Blood Services adjunct scientist Prof. Nancy Heddle, the McMaster Transfusion Research Program (MTRP) is acting as the Canadian Clinical Research Officer (CRO). Canadian Blood Services is supplying pathogen inactivated (Mirasol Pathogen Reduction technology, TerumoBCT) platelet concentrates in plasma for this study. Enrolment for this trial is Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 12 expected to be completed in 2016. This trial will provide information for the implementation of pathogen inactivation technologies in Canada. In a study funded by Canadian Blood Services / CIHR, Canadian Blood Services’ medical officer Dr. Donald Arnold from McMaster University has been investigating the mechanisms behind immune thrombocytopenia (ITP) and their association with clinical outcomes. People with ITP have a low platelet count and, as platelets control bleeding, a tendency to bleed. There are multiple possible causes, but, broadly speaking, in ITP either platelets are being destroyed, often by an immune mechanism, or insufficient platelets are being made by megakaryocytes, the large precursor cells of platelets that are found in the blood marrow. Dr. Arnold and his team developed a tool for growing healthy megakaryocytes in the laboratory.63 Using this megakaryopoiesis tool, the researchers have screened serum from ITP patients and healthy controls to determine whether megakaryocytes respond differently. Initial results suggest that compared to healthy controls, megakaryocyte growth may be slowed when serum from ITP patients is added. The researchers are currently working to improve this assay and to isolate the factors in serum that may be responsible for the effect. Together with Canadian Blood Services’ medical consultant Dr. Michelle Zeller, Dr. Arnold has authored a manuscript on optimal ITP treatment strategies, including one that showed that using a thrombopoietin receptor agonist was associated with improved platelet counts and fewer IVIG (intravenous immunoglobulin) infusions for most patients, and should reduce the need for reliance on platelet transfusions.64 Research from Canadian Blood Services’ scientist Dr. Heyu Ni has also been exploring platelet generation. Dr. Ni’s group has begun investigations into thrombopoietin, a hormone that regulates the production of platelets from megakaryocytes. They found that mice lacking a platelet receptor called GPIbα have less thrombopoietin, indicating that this receptor may be important in thrombopoietininduced platelet production. These findings were presented as an oral presentation at the American Society of Hematology meeting in December 2015 and could have implications for understanding basic platelet biology and in better understanding ITP and its treatments.65 Blood products: Plasma, plasma products, and plasma product replacement Plasma is the protein-rich liquid component of blood that supports the immune system and controls excessive bleeding. It is transfused to prevent or treat bleeding. Canadian Blood Services distributes approximately 135,000 plasma doses annually. Plasma may be directly used for transfusion in patients, or it can be processed into cryoprecipitate and cryosupernatant plasma. These two plasma derivatives are enriched in different clotting factors needed by different patients. Additionally, much of the plasma collected by Canadian Blood Services is sent to international companies for fractionation to make plasma-derived protein products such as IVIG. Current regulations require cryoprecipitate plasma, once thawed, to be kept at ambient temperature and transfused within 4 hours. The laboratory of Canadian Blood Services’ senior scientist Dr. William Sheffield, with Craig Jenkins from the product and process development group, showed that extending this storage period to 24 hours resulted in no significant losses in activity of the four key proteins within this product: fibrinogen; von Willebrand factor; factor XIII; and factor VIII.66 As cryoprecipitate is often pooled prior to transfusion, the team also examined two different pooling methods, again finding no significant difference in factor retention between the methods. These results could lead to regulatory Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 13 changes and reductions in wastage of this plasma-derived product, provided that the extension in storage time does not provide an opportunity for bacterial growth. Based on previous work from Dr. Sheffield, Dr. Ramirez-Arcos and Craig Jenkins, in early 2016 a Health Canada license amendment was made to extend the post-thaw storage of another plasma product, cryosupernatant plasma, from 24 hours to 5 days post-thaw. IVIG is a plasma-derived protein product that contains the pooled antibodies of thousands of donors. Used for a variety of diseases, and often off-label, IVIG is an expensive treatment option. Finding alternatives to IVIG is an active area of research, the first step of which is to better understand how IVIG works. Understanding how IVIG and other immune globulin plasma protein products work in different diseases and exploring potential replacement products continued to be a prime focus for Canadian Blood Services research efforts over the past year. IVIG is often the drug of choice to treat ITP, but it is in limited supply, extremely expensive, and its efficacy varies from patient to patient. Work from the laboratory of Dr. Ni showed that in some patients with ITP in whom IVIG therapy is ineffective, drugs called sialidase inhibitors could be effective. This research showed that anti-GP1bα antibodies implicated in the destruction of platelets in ITP, induce platelet desialylation, and that inhibiting sialidase ameliorated anti-GPIbα-mediated platelet loss in mice.67 Taking these findings into the clinic, an ITP patient who had anti-GPIb autoantibody who was refractory to other treatments was successfully treated with a sialidase inhibitor. The Ni laboratory, in collaboration with colleagues in Dr. Alan Lazarus’ laboratory, also demonstrated that CD8+ T cells limit the severity of thrombocytopenia and are required for an efficacious response to steroid therapy.68 These newly described mechanisms of platelet destruction in ITP suggest potential new ways to diagnose and treat this bleeding disorder. Using a test to identify patients who will not respond to IVIG could prevent unnecessary use of this drug and limit harmful side effects in patients who will not benefit from receiving this treatment in the first place. Importantly, this research also shows that platelet destruction in the liver can be blocked using sialidase inhibitors.69 Sialidase inhibitors are commercially available as antiinfluenza drugs and may be a potential treatment for ITP patients who do not respond to other treatments. The Ni laboratory also made advances in understanding the mechanism of fetal and neonatal Our research challenges the idea that low alloimmune thrombocytopenia or FNAIT, a severe platelet counts are responsible for fetal and potentially fatal bleeding disorder in fetuses and newborns in which maternal antibodies attack fetal brain bleeds and instead shows that the platelets. This work demonstrated for the first time immune system's attack on the new blood that the intracranial bleeds associated with FNAIT, vessel cells in the brain are more likely which can lead to brain damage, death, and loss of the responsible. fetus, are caused by more than just low platelet Dr. Heyu Ni counts. Antibodies against beta 3 integrin prevented proper formation of blood vessels in the brain and in the eye, strongly suggesting that the major cause of intracranial bleeding is impairment of blood vessel formation.70, 71 This research changes the previously held view of what causes intracranial bleeding in FNAIT. It opens other research questions for investigation: how beta 3 integrin contributes to blood vessel formation; and how platelets contribute to blood clotting in developing fetuses. Importantly, this research suggests that giving IVIG may prevent intracranial bleeds associated with FNAIT. Dr. Lazarus’ laboratory provided new insights into the mechanism of action of anti-D and a potential replacement product. The RhD antigen is a clinically important human blood group that can be a primary target in hemolytic disease of the fetus and newborn (HDFN), a condition in which an RhD-negative mother generates antibodies against her RhD-positive baby that can cause destruction of baby’s red blood cells. Polyclonal anti-D is a pooled donor-derived plasma product that is supplied by Canadian Blood Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 14 Services to doctors for the prevention of HDFN, and it is highly effective for this purpose. In fact, Dr. Alan Lazarus was the recipient of the anti-D works so well that HDFN is now a very rare 2015 Tibor Greenwalt Memorial Award disease in Canada. As a pooled donor-derived and Lectureship from the AABB in product made from plasma, it is desirable to replace recognition of his outstanding contributions it with a laboratory-made recombinant product. to the understanding of immune-mediated However, although anti-D has been highly cytopenias and the development of successful, its inhibitory mechanisms remain poorly recombinant immunoglobulins for specific understood, and understanding these mechanisms is therapies for autoimmune hemolytic anemia the first step in developing alternatives. Dr. and idiopathic thrombocytopenic purpura. Lazarus and his group explored one potential mechanism in a mouse model. They assessed the contribution of FcγR and found that successful inhibition of antibody responses to red blood cells by polyclonal IgG can occur independently of activating or inhibitory FcγR involvement.72 As well as prophylaxis for HDFN, anti-D has been used to treat ITP, although again, its mechanism of action is unclear. In a mouse model, Dr. Lazarus investigated a monoclonal antibody with anti-D-like activity in immune thrombocytopenia. They discovered that this antibody requires Fc domain function for immune thrombocytopenia ameliorative effects.73 In more recent work, Dr. Lazarus and colleagues have been investigating the effects of monoclonal vs. polyclonal antibodies, and their data indicate that monoclonal antibody blends may be as effective as polyclonal antibodies in preventing alloimmunization, paving the way for potential rational design of antibody mixtures to replace anti-D. The Lazarus laboratory, together with Dr. Sheffield’s laboratory, made significant advances toward developing a new therapy for ITP. The researchers engineered a monovalent protein that was a fusion of antibodies against Fc-gamma-RIII and albumin. This novel monovalent protein targets Fc-gamma-RIII but does not cause side effects, providing a first-in-class therapy for antibody-mediated ITP. Recently, albumin-coupled drugs have been approved for the treatment of other disorders, paving the way for this novel fusion protein to be developed as a therapy for ITP. If developed into a therapy, this fusion protein could be a safer treatment for patients, and it could reduce the use of IVIG for ITP, which is very expensive for the health care system. 74, 75 In another collaborative effort, Drs. Lazarus and Sheffield, demonstrated the anti-inflammatory effects of antibodies against CD44, a major leukocyte adhesion molecule. They demonstrated that an anti-CD44 antibody can prevent phagocytosis (destruction) of red blood cells by macrophages and elucidated the specific macrophage pathways involved in this effect. The hope is that this broadly anti-inflammatory CD44 antibody could be used in a number of auto-immune disorders, including ITP, and may represent a viable IVIG replacement in the future.76 Despite IVIG’s success in treating many autoimmune and inflammatory conditions, significant sideeffects of high-dose IVIG are becoming apparent, particularly severe hemolysis in patients that have nonO blood groups. Dr. Branch’s laboratory has proposed underlying inflammation as a potential cause of this hemolysis in patients receiving high-dose IVIG,77 helping understanding of this potentially lifethreatening adverse effect of IVIG. Work supported by a Canadian Blood Services / CIHR grant to understand the mechanisms of ITP was published in the journal Blood this year, and was highlighted in an ‘Inside Blood’ editorial. A study by Canadian Blood Services’ adjunct scientist Dr. John Semple, with collaborators Drs. Lazarus and Ni, used a mouse model of ITP that allowed the contributions of antibody- and CD8+ T-cell-mediated ITP to be studied separately.78 This novel approach revealed a role for B cells in maintaining CD8+ T-cell responses, improving understanding of the mechanism of ITP and helping to develop new strategies to treat this disorder. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 15 Many of the diseases in which IVIG is Normally, when you put white blood cells from two used, often off-label, are autoimmune different people in a test tube together, the cells will disorders. Research by Dr. Scott has led towards a potential novel therapy for proliferate like crazy, generating more immune cells auto-immune disorders, which could help in order to wipe out the other “foreign” cells. The ensure more appropriate utilization of immune reaction turns into a type of warfare. But in IVIG. To address the challenge of our study, when one “side” of white blood cells was alloimmunization, Dr. Scott developed PEGylated, this arms race and attack on one another an approach to fool the immune system did not occur. by camouflaging cellular antigens using polymer grafting with Dr. Mark Scott methoxypolyethylene glycol (mPEG). This approach has been shown to successfully camouflage red blood cell antigens and those on other cells such as leukocytes.79 This year, Dr. Scott’s work has shown that his immunocamouflage approach may lead down an unexpected path. He has found that using immunocamouflaged cells, either in vivo or in vitro leads to a "tolerogenic" state, that is, the immune system becomes more tolerant to foreign tissues or less prone to autoimmune diseases. This change in the immune system is mediated by soluble factors, and further analysis showed that the effect resides almost solely with microRNAs. These microRNAs are short (~22 nucleotides) single-stranded RNA molecules found in all eukaryotes that are key regulators of cellular processes including the immune response. Using a bioreactor approach, Dr. Scott and his group have reproducibly generated and purified this fraction and called it “tolerance agent 1” or TA1. Testing TA1 in a mouse model of diabetes, the researchers demonstrated a “reset” in the mouse’s immune system from a proinflammatory to a more tolerant state, preventing or delaying autoimmune diabetes.80 These findings demonstrate that miRNA-based therapeutics can effectively attenuate or arrest the autoimmune disease processes and may be of significant use in a broad range of autoimmune diseases or in the transplantation of foreign tissues. Hematopoietic stem cells Hematopoietic stem cells can renew themselves and differentiate into the various mature blood cells. They have been used since the 1960s to treat numerous malignant or nonmalignant blood disorders. Canadian Blood Services manages a registry of adult hematopoietic stem cell donors, the OneMatch Stem Cell and Marrow Network. Canadian Blood Services also provides autologous hematopoietic stem cell collection, manufacturing and storage services to a few hospitals. In 2013, Canadian Blood Services launched the Canadian Blood Services’ Cord Blood Bank, a national public cord blood bank. Stem cell transplantation from cord blood is associated with slow cell engraftment leading to long delays in the recovery of mature blood cells, such as platelets. As a result, patients transplanted with stem cells from cord blood require more blood transfusions and may have an extended hospital stay. Recent trials have shown that the expansion of stem cells from cord blood before transplantation could accelerate recovery of mature blood cells. However, recovery of platelets remains problematic. Dr. Nicolas Pineault, in collaboration with Héma-Québec, identified a new means to expand cord blood cells that raise their expansion and improved their capacity to produce platelet when transplanted. This strategy is based on the use of osteoblast conditioned medium (OCM). Initial results are promising, showing that Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 16 OCM induces greater expansion of progenitors that produce mature cells such as neutrophils and platelets compared to standard medium.81 Work is on-going to better understand the impact of OCM on the growth of cord blood hematopoietic stem and progenitors responsible for the production of blood cells and to elucidate the cellular mechanisms. We are trying to create larger numbers of cells through a cellular engineering approach where we place the cord blood cells in a culture to expand them before we transplant them in the patient. The hope is that this approach could help patients recover faster and reduce the need for further interventions. Dr. Nicolas Pineault In a big step forward for cord blood research and development at Canadian Blood Services, Dr. Pineault, together with his colleagues in the product and process development group Ken McTaggart, Craig Jenkins and Dr. Acker, established “NetCAD4Cord”. NetCAD4Cord is a replica of Canadian Blood Services’ cord blood hematopoietic stem cell production process and will allow the group to test, optimize, and develop new processes outside of the production environment. Over the past year, work to set up the laboratory space, replicate all of the operating procedures conducted at the Canadian Blood Services’ Cord Blood Bank, validate the equipment and train staff was completed and NetCAD4Cord has begun quality monitoring and development projects. The product and process development group have also supported the Canadian Blood Services’ Cord Blood Bank in optimizing a thawing protocol that can be used internally for the bank’s stability program as well as externally by stem cell transplant programs for transplantation into patients. There are many aspects to be considered in developing an appropriate protocol. Dr. Pineault tested a number of different thawing solutions, and the amount of thawing solution necessary, temperature and dilution steps were established. The impact of these on cell quality, viability, count and stability post-thaw were assessed, and a protocol that leads to superior post-thaw viability than the previous protocol was chosen. Canadian Blood Services was also invited to participate in a World Marrow Donor Association multicentre study with Héma-Québec. This study aims to standardize a flow cytometry method for thawed cord blood samples, by assessing the reproducibility of flow cytometry-based analyses of CD45+ and CD34 + cord blood cells among the Canadian cord blood banks and a number of European cord blood banks. This method will be used to assess the quality of the cord blood stem cells. Dr. Acker is a collaborator on a project funded by the Ontario Institute for Regenerative Medicine related to the Cellular Therapy for Septic Shock (CISS) clinical trials. The goal of the CISS trial program is to test the safety and efficacy of mesenchymal stem cells for the treatment of septic shock, a devastating critical illness. Led by Canadian Blood Services adjunct scientist Dr. Lauralyn Dr. McIntyre and her research team have the McIntyre and Dr. Duncan Stewart from The potential to deliver exciting new cellular therapy Ottawa Hospital, among other aims this project will determine whether cryopreserved with this project. We hope our expertise in the mesenchymal stem cells are comparable to preservation of cells and tissues at sub-zero fresh ones for multi-centre trials and to temperatures and our experience in biologics determine whether optimized manufacturing and distribution can ultimately cryopreservation strategies result in an help speed up the use of this technology. improved product. Dr. Acker will provide Dr. Dana Devine expertise and conduct experiments related to the development of mesenchymal stem cell cryopreservation protocols. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 17 Organ and tissue donation and transplantation The Centre for Innovation, in consultation with Canadian Blood Services’ organ and tissue donation and transplantation group, supports research that furthers our knowledge in the area of organ and tissue donation and transplantation. Through its James Kreppner Fellowship program, Canadian Blood Services supports Maeghan Toews from the University of Alberta to study legal and policy strategies to optimize organ donation in Alberta. This encompasses a variety of topics in organ donation and transplantation relating to the question of how our organ donation system can be improved in an ethically and legally acceptable manner. The work specifically relates to issues of consent for donation, mandatory referral of potential deceased donors, incentives for living and deceased donation, and donation after cardiocirculatory death. This interdisciplinary project has engaged a wide range of stakeholders including clinicians from the transplant and critical care communities, patient groups, organ donation organizations, and policymakers, as well as other academics in law, ethics, and policy, both within Canada and internationally. The work has contributed to Canadian National Transplant Research Program’s (CNTRP) Fast Policy Facts documents82 and engagement and dissemination has been high, with many speaking engagements as well as dissemination through the media in television, radio, newspaper, and magazine articles and interviews. Also through the James Kreppner fellowship, Prof. Vanessa Gruben from the University of Ottawa has been supported to investigate organ donation in Canada: Engaging with stakeholders and proposing solutions to current legal and ethical challenges. Her work focuses on organ donation after cardiac death (DCD), with the objective of establishing a better understanding of the factors that affect family decisionmaking and their experiences of DCD. Having better information regarding families’ experiences with DCD will subsequently inform the development of policy to increase the number of DCD donors in Canada in a legally and ethically appropriate manner. Prof. Gruben is also studying the legal and ethical aspects of allowing people who are competent and close to death to donate their organs once they are deceased. This is an issue in two populations in Canada: patients who have amyotrophic lateral sclerosis (ALS) and individuals who have requested physician-assisted dying. To date, there is little analysis of the legal and ethical principles that must be considered when an individual in these circumstances makes a request to donate his or her organs and this project seeks to fill this important gap. Canadian Blood Services also funds the Kenneth J. Fyke Award, which supports health services and policy research to promote the development of evidence-based practices and policies in blood transfusion, blood stem cell transplantation, and organ and tissue transplantation for the benefit of Canadian patients. Through this award, Dr. Maureen Meade and Dr. Frederick D’Aragon are conducting an observational study of clinical practices in organ donations. The goal is to observe the medical management of deceased organ donors in six centres in Ontario and Québec, including some specific medical management strategies that are perceived to improve transplant rates. Knowledge translation, quality assurance regarding the accuracy and completeness of collected organ donor data as well as a follow up of organ function in recipients will also be conducted. The study is designed to have immediate clinical relevance in this field and will pave the way for larger Canada-wide multicentre study. Building capacity in transfusion and transplantation science and medicine Salary support To attract and train professionals to the field of transfusion and transplantation sciences and medicine, the Centre for Innovation administers competitive programs designed to support professionals at various stages of their research careers. In the 2015-2016 fiscal year, the Centre supported 42 trainees (Table 1), all of whom are affiliated with a Canadian research academic institution, as undergraduate or graduate Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 18 students, postdoctoral fellows, or new investigators. While the majority of award recipients complete their training under the mentorship of a Canadian Blood Services’ principal investigator or adjunct scientist, nine are currently conducting their training with an external group. Through these award programs, two trainees completed an MSc or PhD during the year and received rigorous training that allow them to be competitive in the health science environment. For example, Dr. Lidice Bernardo Reyes, who received a post-doctoral fellowship to conduct research in Dr. Lazarus’ laboratory, recently secured a scientist position at Sanofi Pasteur in Toronto. Enhancements to the programs are also My Canadian Blood Services post-doctoral being implemented. In particular, over fellowship award, held in Dr. Lazarus laboratory, the last year, senior trainees have been engaged in the review of the training allowed me to develop rigorous research skills and programs and in the peer-review of the prepared me well for my scientist position at Sanofi summer and graduate fellowship Pasteur. applications. These unique experiences Dr. Lidice Bernardo Reyes will enhance their “soft skills”, which are essential in their professional development. In 2015-2016, with financial support from the Centre for Innovation and other partners, the Centre for Blood Research supported 36 postdoctoral fellows and undergraduate and graduate students from the University of British Columbia conducting research in 20 Centre for Blood Research laboratories (Table 1). This unique partnership between the Centre for Innovation and the Centre for Blood Research allows Canadian Blood Services to effectively promote the next generation of researchers in the areas of transfusion medicine and blood-related diseases. Table 1: Number of new, ongoing, and completed training awards in 2015-2016 Program New Ongoing (including renewals) Completed Centre for Innovation training programs Summer internship program 10 n/a 10 internships Graduate fellowship program 4 12 4 graduate fellowships Postdoctoral fellowship program 2 5 3 postdoctoral fellowships New investigator program 0 2 0 1 1 transfusion medicine fellowship Transfusion Medicine Diploma program Transfusion medicine residency fellowship 2 Centre for Blood Research training programs Summer studentship 21 n/a Not recorded by the Centre Graduate award program 7 5 Not recorded by the Centre Postdoctoral transition grant 2 1 Not recorded by the Centre The Centre for Innovation facilitates the training of transfusion medicine specialists by providing salary support to medical fellows enrolled in the Transfusion Medicine Areas of Focused Competency (AFC)Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 19 diploma program. In 2015-2016, two new Transfusion Medicine Residency Fellowships were awarded to fellows completing the diploma at McMaster University and University of British Columbia, and one fellowship for a fellow at McMaster University was renewed. These fellows have already completed their medical training as a clinical hematologist, anesthesiologist, and pediatric hematologist/oncologist, respectively, and are seeking additional transfusion medicine specialty training through the diploma program. Finally, one fellow completed her fellowship at McMaster University during the year and is now an assistant professor at McMaster University, a Canadian Blood Services medical consultant, and a Transfusion Medicine Specialist for the Hamilton Regional Laboratory Medicine Program (Table 1). Courses and diplomas Transfusion medicine camp In 2012, Drs. Yulia Lin and Jeannie Cullum from Sunnybrook Health The best transfusion is the most appropriate Sciences Centre established a transfusion and that’s what we’re teaching residents. “transfusion camp” for University of Toronto post-graduate medical residents Dr. Yulia Lin from critical care, hematology, hematopathology, obstetrics and pediatric hemato-oncology. This five-day-a-year camp ensures that non-transfusion medicine specialists have the knowledge they need to make appropriate decisions when it comes to transfusion. Drs. Robert Skeate, Margaret Fearon and Nadine Shehata from Canadian Blood Services’ medical group deliver lectures for the camp in addition to those taught by the medical faculty. The Centre for Innovation is also partnering with Drs. Lin and Callum, to expand the reach of the “transfusion camp”. In 2015-2016, with the leadership of Dr. Elianna Saidenberg from The Ottawa Hospital, the Centre facilitated the participation of post-graduate medical residents from the University of Ottawa. Seventeen hematopathology residents were able to remotely join the five day camp delivered for University of Toronto residents, and another 11 anesthesiology residents were able to view the recorded lectures. In addition to the lectures, “transfusion camp” shares materials to conduct problem-based learning seminars, as well as pre- and post-tests to evaluate knowledge gain. During the year, representatives from Dalhousie University and University of British Columbia attended lectures to evaluate the program. Several more universities have now confirmed their participation in the 2016-2017 camp that will begin on July 22, 2016, including universities in Hamilton, Ottawa, Kingston, London, Halifax, Vancouver, and Oxford (UK). The Centre for Innovation committed staff and technology (e.g., GoToWebinar and SharePoint software) to facilitate webcasting, lecture recording, and dissemination of materials, helping to make the expansion of the transfusion camp a success. This partnership is one way the Centre demonstrates its commitment to education and knowledge sharing to promote excellence in transfusion practice. Transfusion medicine diploma program The Transfusion Medicine diploma program is an Areas of Focused Competency (AFC)-Diploma Program in Transfusion Medicine accredited by the Royal College of Physicians and Surgeons of Canada. The program is delivered in partnership between five Canadian universities and Canadian Blood Services. Established in 2001, the program has been essential in establishing a strong physician community of transfusion medicine specialists in Canada. The Canadian Blood Services component of the diploma program is now led by Dr. Skeate, and several members of the Canadian Blood Services’ medical group are also course directors at their local medical schools (Dr. Tanya Petrazsko at University British Columbia, Dr. Arnold at McMaster University, Dr. Wendy Lau at University of Toronto). In 2015-2016, partnerships were established to further expand the program. A partnership was developed with the University of Alberta to enable the participation of one of their transfusion medicine fellows in Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 20 the Canadian Blood Services’ component of the diploma program. In addition, Canadian Blood Services has established a partnership with Héma-Québec and the University of Toronto to facilitate the completion of the diploma program by fellows from Québec. One Héma-Québec fellow completed her fellowship during the year and a second started her fellowship. These partnerships strengthen the national impact of the Transfusion Medicine diploma program and thus the Canadian transfusion community. Education events In 2015-2016, the Centre for Innovation delivered, on its own or in partnership, 72 education events, which attracted an estimated 7700 professionals (Table 2). Staff from the Centre for Innovation organize an annual international symposium. This year’s symposium focused on blood-borne pathogens, a theme that is pertinent to the ongoing discussion around the potential implementation of pathogen inactivation technology in North America. Co-chaired by Drs. Sheffield and Webert, the symposium updated physicians, medical laboratory technologies, and researchers on current knowledge and challenges in the field. The presentations, delivered by four international and four national experts, focused on three themes: defense against pathogens; detection of pathogens; and destruction of pathogens. The Continuing Medical Education-accredited event was wellreceived by attendees, and the majority (98%) agreed that the event enhanced their knowledge in a manner that was applicable to their work or practice. To further disseminate the knowledge shared at this one-day event, the presentation slides for seven of the presentations are available on www.transfusionmedicine.ca. In addition, a symposium report was published in Transfusion Medicine Reviews.83 Through the Program Support Award to the Centre for Blood Research and the activities of Canadian Blood Services scientists located at the Centre for Blood Research, the Centre for Innovation contributed to the Annual Norman Bethune Symposium, the Centre for Blood Research’s Research Day, and the Earl W. Davie Symposium. Attendance at these events reached almost 200 attendees. The events were also broadcasted live and archived on the Centre for Blood Research website. The Program Support Award also allows the Centre for Innovation to contribute to the Centre for Blood Research Seminar series, which have average attendance of 80-140 attendees and are also broadcasted live to increase the reach of the events. The Centre for Innovation, with the leadership of Canadian Blood Services’ Through these partnered educational events, medical directors, works in partnership Canadian Blood Services and ORBCoN promote best with provincial blood coordinating transfusion practices to over 800 health care offices to deliver educational events. professionals every year. These events are targeted primarily to health-care professionals working in Dr. Peter Lesley Canadian hospitals and involved in the transfusion of blood products and are essential for their continued learning. The events highlight new practices and guidelines and provide access to experts, who may not be available in smaller hospitals. Dr. Peter Lesley, with the Ontario Regional Blood Coordinating Network (ORBCoN), co-organized the 10th Annual Northern and Eastern Ontario Annual Transfusion Medicine Education Videoconference. The 2015 program focused on “Patient Blood Management: Optimizing Patient Outcomes”. To increase the reach of this videoconference, the Knowledge Mobilization group organized “Knowledge to Munch On: Focus on Clinical Education” to allow Canadian Blood Services’ staff from across Canada to attend the event. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 21 Table 2: Key education events organized by the Centre or delivered in partnership in 2015-2016 Event (Location) Primary Partner # of Attendees Audience 120 Health care professionals, researchers, industry representatives, Canadian Blood Services staff “Knowledge to Munch On” N/A Webinar series – five events (Webinar) 155, 147, 134, 146, 156 Canadian Blood Services staff and volunteers, American Red Cross staff, Health Canada staff Learn Transfusion Seminar Canadian Blood Series – 23 events Services medical (Webinar) directors 50 per event Health care professionals Events led by the Centre for Innovation Canadian Blood Services Annual International Symposium (Toronto) N/A Events delivered in partnership Norman Bethune symposium (Vancouver, broadcast) Centre for Blood Research 200 Researchers, health care professionals, basic science and clinical trainees, members of the public, industry representatives, Canadian Blood Services staff Earl W. Davie symposium (Vancouver, broadcast) Centre for Blood Research 190 Researchers, health care professionals, basic science and clinical trainees, members of the public, industry representatives, Canadian Blood Services staff CBR Research Day (Vancouver) Centre for Blood Research 180 Researchers, health care professionals, basic science and clinical trainees, members of the public, industry representatives, Canadian Blood Services staff Centre for Blood Research Centre for Blood weekly seminar series – 31 Research events (Vancouver, broadcast) 80-140 per event Researchers, health care professionals, basic science and clinical trainees, members of the public, industry representatives, Canadian Blood Services staff Centre for Blood Research Centre for Blood summer seminar series – Research eight events (Vancouver) 80-140 per event Researchers, health care professionals, basic science and clinical trainees, members of the public, industry representatives, Canadian Blood Services staff 10th Annual Transfusion Medicine Symposium (Ottawa, broadcast) Ontario Regional Blood 841 Coordinating Network Health care professionals primarily in northern and eastern Ontario, Canadian Blood Services staff Canadian Blood Services leverages national and international events to educate the community. The Centre for Innovation contributes financially to the Canadian Society for Transfusion Medicine Annual Meeting and, in collaboration with Héma-Québec and other key members of the transfusion community, Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 22 develops the scientific and workshop programs. In 2015, Dr. Debra Lane was a member of the scientific committee that identified topics of importance. The International Society on Thrombosis and Haemostasis 2015 Congress was held in Toronto. Dr. Arnold was the chair of the transfusion scientific program subcommittee and Drs. Ni and Pryzdial were on the platelets and coagulation factors and inhibitors scientific subcommittees, respectively. Through the BloodTechNet competition, the Centre for Innovation funds In addition to recruiting stem cell donors, our stem innovative projects aimed at delivering cell club equips medical students with leadership educational tools and resources that opportunities and skills to become health advocates support the development of skills, for patients in need. Our initiative empowers students knowledge, and expertise of health to become leaders in Canadian healthcare. professionals in the transfusion, cellular therapy, and transplantation communities Dr. Warren Fingrut in Canada. In 2015, Dr. Warren Fingrut received funding for “The Stem Cell Club: Educating Medical Students about Stem Cell Transplantation”. The Stem Cell Club, which equips medical students with skills to become health advocates for patients in need of stem cell transplants, is developing an evidence-based volunteer training program that can be expanded nationally. Internally, the Centre for Innovation provides educational opportunities to Canadian Blood Services’ staff across the organization through “lunch and learn” webinars. These events, organized by the Centre’s staff, showcase presentations by Canadian Blood Services’ research groups and highlight the impact of ongoing research projects on the blood system and operators. To expand the reach of these events, invitations are extended to colleagues from Health Canada and American Red Cross, as well as Canadian Blood Services volunteers. To further extend the reach of these events, recordings are available on the Canadian Blood Services intranet for Canadian Blood Services’ staff. Over the last year, five events were organized attracting a total of 738 attendees. Education materials Original articles and resources The Centre for Innovation manages www.transfusionmedicine.ca, an education website for health-care professionals involved in transfusion of blood products. The site provides original resources, as well as links to reliable resources developed by other organizations. The Centre for Innovation, with the editorial leadership of Canadian Blood Services Medical Associate Dr. Gwen Clarke, publishes regular updates to the “Clinical Guide to Transfusion”. This invaluable online resource for health-care professionals is written in collaboration with Canadian Blood Services’ medical group and Canadian experts. The 18-chapter guide provides a practical summary, in both English and French, of our current knowledge of blood components and transfusion medicine practices. During the last year, four chapters were updated.84-87 In 2015-2016, in addition to updates to the Clinical Guide to Transfusion, the following original resources were published. “Molecular immunohematology at Canadian Blood Services: red cell antigen genotyping” by Drs. Goldman, Kristin Hannaford, Judith Hannon, and Philip Berardi.88 Eight ResearchUnits, which provide clear summaries of the results and impacts of research conducted at Canadian Blood Services, were published.10, 20, 21, 30, 35, 44, 74, 89 Written by Canadian Blood Services’ researchers in collaboration with the Knowledge Mobilization group, these summaries help in the dissemination of research findings to facilitate informed decision-making.90 Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 23 Science communication This year the Centre for Innovation, in collaboration with Canadian Blood Services’ Public Affairs division, launched several new science communication initiatives. Compiled by science communications specialist Jenny Ryan, a monthly Research and Education Round Up was launched on Aug 31, 2015. This monthly electronic newsletter delivers information, including news, events, publications and resources about the activities of Canadian Blood Services’ Medical Services and Innovation research and education network. The initial distribution of this newsletter was predominantly internal: the Canadian Blood Services Medical Services and Innovation research and education network; the Executive Management Team, the Board of Director and Public Affairs. After an initial trial period, the newsletter was launched as a “Mail Chimp” version in October 2015. The newsletter currently has 196 subscribers, both internal and external, and an open rate of 40 per cent, which compares favorably to the industry average rate of 23 per cent. Total opens for each newsletter edition is around 300 or more, suggesting subscribers are sharing the newsletter with colleagues. Beginning in April 2016, the Research and Education Round Up was made available for the public to subscribe. Launched on Feb 10, 2016, RED – our research, education, and discovery blog can be found on the publicly accessible blood.ca website. The blog aims to tell Canadian Blood Services’ research, education and discovery stories, as well as to introduce the people and places behind our research in blood science and transfusion medicine and cellular therapies (in particular blood stem cells), as well as organ and tissue transplantation. This medium has proved highly impactful, particularly its integration with social media: the most-read post has been read over 600 times; five posts on Facebook reached about 42,000 people; six research-related tweets on Twitter received about 30,000 impressions. In addition to showcasing the work of the Centre for Innovation, the blog stories provide a new approach to educate the public in transfusion and transplantation science and medicine. Leveraging expertise through collaborations As demonstrated by the many research projects and education activities highlighted in this report, the Centre for Innovation leverages internal expertise and the expertise of external stakeholders through formal and informal arrangements. In the last year, 38 new formal partnerships were established or renewed. This collaborative approach allows the Centre to extend its reach while remaining within its financial and expertise constraints. In this section, large collaborative activities are highlighted. Clinical guidelines and leading practices Health-care systems around the world are experiencing rising health-care costs, fueled by increased demand for care, more expensive technologies, and an aging population. Clinical guidelines and leading practices, combined with effective knowledge translation and implementation strategies, help address this problem by improving patient care and outcomes while at the same time increasing efficiencies through reduction of inappropriate and unnecessary treatments. Research in donation and transfusion and transplantation medicine has evolved substantially in the past 20 years. As more studies and clinical trials are conducted, the body of evidence has grown and, with it, the ability to develop timely, evidence-based clinical guidelines and leading practices. As part of knowledge mobilization work led by Sylvia Torrance, Centre for Innovation Associate Director Policy Research and Leading Practices, the Centre is in the process of developing a standardized methodology for the development of systematic reviews, clinical practice guidelines, and leading practices. Bringing together Canadian Blood Services expertise in organs and tissues, stem cells, and transfusion, the methodology Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 24 being developed follows internationally recognized processes, such as those described by Cochrane, GRADE, and AGREE II. It is expected to improve the quality, credibility, relevance, and ease of implementation of guidelines and good practices developed at Canadian Blood Services. Globally, many organizations have recognized the opportunity to reduce the costs of developing clinical guidelines by eliminating duplication through collaboration and alignment of priorities. The Centre for Innovation has initiated discussions with various international partners to explore potential solutions. More specifically for transfusion practice, the Centre for Innovation continues to support the International Collaboration for Transfusion Medicine Guidelines (ICTMG) group, under the leadership of Dr. Nadine Shehata. The ICTMG consists of transfusion medicine experts from eight countries. In 2015, the group conducted three systematic reviews that are being used to develop evidence-based recommendations for two clinical practice guidelines: management of fetal and neonatal alloimmune thrombocytopenia and red cell specifications for patients with hemoglobinopathies. Both guidelines deal with conditions that can have serious health impacts on patients, and the goal is to decrease morbidity and mortality in these patient groups. The ultimate goal of the ICTMG is to influence clinical practice in order to improve patient care. Recognizing that digital technology and social media are effective ways of disseminating knowledge to health care professionals, the group is developing tools to support the implementation of its guidelines and a website to ensure effective access to those tools. Blood operations As a member of the Alliance of Blood Operators (ABO), Canadian Blood Services participates in international collaborative activities aimed at strengthening the operations of blood operators and the blood system in general. Over the last year, the Centre for Innovation internal network of medical and scientific experts contributed to the annual ABO horizon scan. This scan provides a view into global trends in the blood sector, such as the protracted decline in demand for red blood cells and fresh plasma, the potential impact of personalized medicine on transfusion practice, and the effect of social changes on blood donor recruitment and retention. The scan provides an opportunity for members to share views on the potential impact and alternative management approaches to some key common issues and to identify opportunities for a shared approach. Another key activity of the ABO is to facilitate knowledge exchange across its membership to identify and promote good practice and encourage performance improvement. The exchange of information under the ABO Confidentiality Agreement facilitates timely access to such information. Finally, over the last year, eight ABO members have developed a common framework to better understand the research and development programs led by their respective organizations. While in its infancy, the framework will facilitate the development of best practices to improve research and development program performance, and it may promote collaborative initiatives. Blood safety The Risk-Based Decision-Making (RBDM) Framework for Blood Safety, which was created under the auspices of the ABO with the leadership of Judie Leach-Bennett and Sheila Ward of the Centre for Innovation, was published online in September 2015, along with multiple tools. Access to this toolkit facilitates the application of RBDM to blood safety decisions Blood operators are currently using the RBDM toolkit for real-time blood safety decisions. For example, Canadian Blood Services has completed an assessment of the current and long-term risk of Babesia to the national blood supply91 and is now using the framework to undertake an analysis of Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 25 cytomegalovirus screening;92 Australia is assessing options for management of HTLV-1 screening; and the UK is considering options for changes to acupuncture deferral. The Centre for Innovation is also assisting the AABB in using the RBDM framework and tools to assess the risk of Babesia to the United States’ blood supply. Global collaboration will enable blood operators to share risk data and analyses in order to optimize the safety of the blood supply for patients, to allocate resources in proportion to the magnitude and seriousness of the risk, and to assess and incorporate the medical/scientific, social, economic, and ethical factors that may affect decisions about risk. The RBDM framework and tools can be found at https://riskframework.allianceofbloodoperators.org. Research services The Centre for Innovation continues to facilitate blood and cord blood research by providing unique research products to reseachers across Canada. Through Canadian Blood Services netCAD facility in Vancouver, researchers have access to the gamut of blood products. Those products are collected from deferred donors and thus contribute to the continued positive engagement of those donors with Canadian Blood Services. In 2015-2016, a total of 1974 research products (which include apheresis and pooled platelets, buffy coats, plasma, red cell units, whole blood units, specimen tubes and apheresis chambers) were distributed to 50 research projects (31 internal and 19 external to the Centre) across Canada. The Cord Blood for Research Program, established in 2014 by the Cente for Innovation in partnership with the Cord Blood Bank, continued to provide valuable research samples. In the last year, 236 cord blood samples were distributed to 11 projects across Canada. In addition, the group has developed processes to distributed frozen cord blood stem cell samples to researchers. This new research product will be made available to the research community in July 2016. Governance Canadian Blood Services continues to provide a sound governance structure for the Centre for Innovation research and education program. Oversight is provided by the external Scientific & Research Advisory Committee and by the Safety, Research & Ethics Committee of Canadian Blood Services’ Board of Directors. Specific research ethics oversight is provided by Canadian Blood Services’ Research Ethics Board (REB), in accordance with the provisions of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans -- TCPS 2 (2014). In 2015-2016, the REB reviewed 37 new research applications and renewed 62 applications, to ensure adherence to national ethics standards by all research projects supported by Canadian Blood Services. Complementing the work of the REB, a new element of bioethics oversight was introduced this year in order to address increasingly complex ethical challenges associated with emerging medical procedures and technologies as well as biological discoveries and biomedical advances. In response to emerging trends related to the biological products and services Canadian Blood Services offers, an external Bioethics Advisory Committee has been established, with the leadership of the Centre for Innovation, to inform policy development and education in the application of ethical principles to these system-level ethical challenges. In addition, there has been continued attention to good governance practices in the administration of Centre for Innovation programs. All competitive research and training funding programs (11 competitions) have been conducted by the Centre for Innovation with strictly observed peer-review processes and appropriate financial controls. In addition, a SharePoint platform was implemented to optimize efficiency in the peer-review process. These and all other Centre for Innovation programs are governed by a Performance Measurement Framework. The Centre for Innovation reports on performance and progress against stated objectives and an annual workplan, as well as on overall impact, to Canadian Blood Services’ Executive Management Team and Board of Directors, Health Canada, and to the Provincial/Territorial Blood Liaison Committee. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 26 References cited (see Appendix II for a full list of the Centre for Innovation’s publications for fiscal year 2015-2016) 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. O'Brien SF, Osmond L, Choquet K, Yi QL, Goldman M. Donor attention to reading materials. Vox Sang. 2015. Acker J, Howell A, Turner T, Yi Q. Evaluation of a point-of-care hemoglobinometer for measuring donor hemoglobin. Transfusion. 2015; 55: 98A. Howell A, Acker J. Compolab hemoglobinometer evaluation. Internal report submitted to Canadian Blood Services, Susan Shimla, Collections Process Management. 2015. Blake J. Methods for estimating donor deferrals with the CompoLab hemoglobin measurement system. Internal report submitted to Canadian Blood Services. 2015. O’Brien S, Osmond L, Goldman M. Impact of a 5-year deferral for men who have sex with men on donor compliance. Transfusion. 2015; 55: 21A. O'Brien SF, Osmond L, Fan W, Yi Q-L, Goldman M. Impact of a 5-year deferral from blood donation for men who have sex with men. Transfusion. 2015. O'Brien S, Osmond L, Goldman M, Fearon M. Donor travel survey. Canadian Society for Transfusion Medicine Website. 2015. Simon AY, Sutherland MR, Pryzdial ELG. Dengue virus binding and replication by platelets. Blood. 2015; 126: 378-85. Sutherland MR, Simon AY, Serrano K, Schubert P, Acker JP, Pryzdial ELG. Dengue virus persists and replicates during storage of platelet and red blood cell units. Transfusion. 2016. Pryzdial EL. ResearchUnit: Hijacked: The role of platelets in dengue virus infection revealed. transfusionmedicine.ca website. 2016. Fearon M, Skeate R, Bigham M, Cronin P, Biemans J, Guenette K, McIntyre L, Shimla S, Dunbar M. Ebola preparedness at Canadian Blood Services. Canadian Society for Transfusion Medicine Website. 2015. McCarthy SDS, Majchrzak-Kita B, Racine T, Kozlowski HN, Baker DP, Hoenen T, Kobinger GP, Fish EN, Branch DR. A rapid screening assay identifies monotherapy with interferon-ß and combination therapies with nucleoside analogs as effective inhibitors of Ebola virus. PLoS Negl Trop Dis. 2016; 10: e0004364. Fish EN, McCarthy SD, Hoenen T, Branch DR. Ifn-β treatment for Ebola virus disease: Bench to bedside. Cytokine. 2015; 76: 77. Veljkovic V, Goeijenbier M, Glisic S, Veljkovic N, Perovic VR, Sencanski M, Branch DR, Paessler S. In silico analysis suggests repurposing of ibuprofen for prevention and treatment of ebola virus disease. F1000Res. 2015; 4: 104. Gray N, Newbold KB, Lane SJ, Heddle NM, Webert K, Eyles J. Public perceptions of pathogen reduction technology in the Canadian donor blood supply. ISBT Sci Ser. 2015. Webert KE. Splitting versus lumping: Reconsidering the definition of transfusion-related acute lung injury. Transfusion. 2015; 55: 927-9. Kapur R, Kim M, Shanmugabhavananthan S, Liu J, Li Y, Semple JW. C-reactive protein enhances murine antibody–mediated transfusion-related acute lung injury. Blood. 2015; 126: 2747-51. Tabuchi A, Nickles HT, Kim M, Semple JW, Koch E, Brochard L, Slutsky AS, Pries AR, Kuebler WM. Acute lung injury causes asynchronous alveolar ventilation that can be corrected by individual sighs. Am J Respir Crit Care Med. 2015; 193: 396-406. Goldman M, Lane D, Webert K, Fallis R. The prevalence of anti-K in canadian prenatal patients. Transfusion. 2015; 55: 1486-91. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 27 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. Goldman M. ResearchUnit: ABO...K? Investigating if young females need more than ABOcompatible blood. Transfusionmedicine.ca website. 2015. Heddle NM, Acker JP. ResearchUnit: Data mining: Digging for deeper understanding of blood components and transfusion outcomes. Transfusionmedicine.ca website. 2016. Heddle NM, Arnold DM, Acker JP, Liu Y, Barty RL, Eikelboom JW, Webert KE, Hsia CC, O'Brien SF, Cook RJ. Red blood cell processing methods and in-hospital mortality: A transfusion registry cohort study. Lancet Haematol. 2016. Chassé M, A T, English S, McIntyre L, Knoll G, Wolfe D, Wilson K, Shehata N, Forster A, van Walraven C, Fergusson DA. Effect of blood donor characteristics on transfusion outcomes: A systematic review and meta-analysis. Transfusion. 2015; 55: 123A. Chasse M, McIntyre L, Tinmouth A, English S, Acker J, Knoll G, Forster A, Shehata N, Wilson K, Ducharme R, van Walraven C, Fergusson D. Clinical effects of blood donor characteristics in transfusion recipients: A framework to study the blood donor-recipient continuum. Transfusion. 2015; 55: 42A. Lacroix J, Hébert PC, Fergusson DA, Tinmouth A, Walsh T, Stanworth S, Campbell H, Boyd J, Burrows H, Hemmatapour S, on behalf of the Canadian Critical Care Trials Group. A randomized controlled trial comparing the outcome of critically ill adults who received fresher vs. Older red cells units. ISBT Sci Ser. 2016; 11: 332-6. Spinella PC, Acker J. Storage duration and other measures of quality of red blood cells for transfusion. JAMA. 2015; 314: 2509-10. Jordan A, Chen D, Devine D, Acker J. Using blood bank quality control data to analyze manufacturing and donor variability. Transfusion. 2014; 54: 42A. Bicalho B, Pereira AS, Acker JP. Buffy coat (top/bottom)- and whole-blood filtration (top/top)produced red cell concentrates differ in size of extracellular vesicles. Vox Sang. 2015; 109: 21420. Bakkour S, Acker J, Turner T, Chafets D, Lee T, Busch M. Processing method affects release of mitochondrial DNA damage-associated molecular patterns (DAMPs) in stored red blood cells. Transfusion. 2015; 55: 80A. Serrano K. ResearchUnit: Making the cut: Protein breakdown in platelets during storage. Transfusionmedicineca website. 2015. 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 paediatricsized polyvinylchloride bags plasticized with alternatives to di-2-ethylhexyl phthalate (DEHP). Vox Sang. 2015. Bicalho B, Serrano K, dos Santos Pereira A, Devine D, Acker J. Blood bag plasticizers influence red blood cell vesiculation rate without altering the lipid composition of the vesicles. Transfus Med Hemother. 2015. Briard JG, Poisson JS, Turner TR, Capicciotti CJ, Acker JP, Ben RN. Small molecule ice recrystallization inhibitors mitigate red blood cell lysis during freezing, transient warming and thawing. Sci Rep. 2016; 6: 23619. Capicciotti CJ, Kurach JDR, Turner TR, Mancini RS, Acker JP, Ben RN. Small molecule ice recrystallization inhibitors enable freezing of human red blood cells with reduced glycerol concentrations. Sci Rep. 2015; 5. Acker JP. ResearchUnit: Bath time for blood cells: Improving the red blood cell washing process. Transfusionmedicineca website. 2015. Hansen A, Yi QL, Acker JP. Quality of red blood cells washed using the ACP 215 cell processor: Assessment of optimal pre- and postwash storage times and conditions. Transfusion. 2013; 53: 1772-9. Hansen AL, Turner TR, Yi QL, Acker JP. Quality of red blood cells washed using an automated cell processor with and without irradiation. Transfusion. 2014; 54: 1585-94. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 28 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. 54. 55. Hansen AL, Turner TR, Kurach JDR, Acker JP. Quality of red blood cells washed using a second wash sequence on an automated cell processor. Transfusion. 2015. Acker JP, Hansen AL, Yi Q-L, Sondi N, Cserti-Gazdewich C, Pendergrast J, Hannach B. Introduction of a closed-system cell processor for red blood cell washing: Postimplementation monitoring of safety and efficacy. Transfusion. 2016; 56: 49-57. Atkins CG, Buckley K, Chen D, Schulze HG, Devine DV, Blades MW, Turner RFB. Raman spectroscopy of stored red blood cells: Evaluating clinically-relevant biochemical markers in donated blood. Clinical and Biomedical Spectroscopy and Imaging IV. 2015; 9537: 95370X. Buckley K, Atkins CG, Chen D, Schulze HG, Devine DV, Blades MW, Turner RFB. Noninvasive spectroscopy of transfusable red blood cells stored inside sealed plastic blood-bags. Analyst. 2016; 141: 1678-85. Matthews K, Myrand-Lapierre M-E, Ang RR, Duffy SP, Scott MD, Ma H. Microfluidic deformability analysis of the red cell storage lesion. J Biomech. 2015; 48: 4065-72. Kwan DH, Constantinescu I, Chapanian R, Higgins MA, Kotzler MP, Samain E, Boraston AB, Kizhakkedathu JN, Withers SG. Toward efficient enzymes for the generation of universal blood through structure-guided directed evolution. J Am Chem Soc. 2015; 137: 5695-705. Withers SG, Kizhakkedathu J. ResearchUnit: Breakthrough brings universal blood a step closer to reality. Transfusionmedicineca website. 2015. Wen J, Weinhart M, Lai B, Kizhakkedathu J, Brooks DE. Reversible hemostatic properties of sulfabetaine/quaternary ammonium modified hyperbranched polyglycerol. Biomaterials. 2016; 86: 42-55. Singh S, Dubinsky-Davidchik IS, Yang Y, Kluger R. Subunit-directed click coupling via doubly cross-linked hemoglobin efficiently produces readily purified functional bis-tetrameric oxygen carriers. Org Biomol Chem. 2015; 13: 11118-28. Siren EM, Singh S, Kluger R. Bioorthogonal phase-directed copper-catalyzed azide–alkyne cycloaddition (pdcuaac) coupling of selectively cross-linked superoxide dismutase dimers produces a fully active bis-dimer. Org Biomol Chem. 2015; 13: 10244-9. Chang TMS. Red blood cell replacement, or nanobiotherapeutics with enhanced red blood cell functions? Artif Cells Nanomed Biotechnol. 2015; 43: 145-7. Bian Y, Guo C, Chang T. Temperature stability of poly-[hemoglobin-superoxide dismutasecatalase-carbonic anhydrase] in the form of a solution or in the lyophilized form during storage at −80°C, 4°C, 25°C and 37°C or pasteurization at 70°C. Artif Cells Nanomed Biotechnol. 2016; 44: 41-7. Guo C, Gynn M, Chang T. Extraction of superoxide dismutase, catalase, and carbonic anhydrase from stroma-free red blood cell hemolysate for the preparation of the nanobiotechnological complex of polyhemoglobin–superoxide dismutase–catalase–carbonic anhydrase. Artif Cells Nanomed Biotechnol. 2015; 43: 157-62. Ramirez-Arcos S. Ten years of platelet screening for bacterial contamination at canadian blood services. Internal report submitted to Canadian Blood Services. 2015. Ramirez-Arcos S, Kou Y, Taha M, Goldman M. Evaluation of alternative skin disinfection methods for donors allergic to chlorhexidine. Canadian Society for Transfusion Medicine Website. 2015. Ramirez-Arcos S, Kou Y, Taha M, Goldman M. Selecting an alternative skin disinfection method for donors allergic to chlorhexidine at canadian blood services. Vox Sang. 2015; 109: 74. Loza-Correa M, Perkins H, Kumaran D, Kou Y, Qaisar R, Geelhood S, Ramirez-Arcos S. Noninvasive pH monitoring for bacterial detection in platelet concentrates. Transfusion. 2016. 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. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 29 56. 57. 58. 59. 60. 61. 62. 63. 64. 65. 66. 67. 68. 69. 70. Corduan A, Ple H, Laffont B, Wallon T, Plante I, Landry P, Provost P. Dissociation of serpine1 mRNA from the translational repressor proteins ago2 and tia-1 upon platelet activation. Thromb Haemost. 2015; 113: 1046-59. Laffont B, Corduan A, Rousseau M, Duchez AC, Lee CH, Boilard E, Provost P. Platelet microparticles reprogram macrophage gene expression and function. Thromb Haemost. 2016; 115: 311-23. Duchez AC, Boudreau LH, Naika GS, Bollinger J, Belleannee C, Cloutier N, Laffont B, Mendoza-Villarroel RE, Levesque T, Rollet-Labelle E, Rousseau M, Allaeys I, Tremblay JJ, Poubelle PE, Lambeau G, Pouliot M, Provost P, Soulet D, Gelb MH, Boilard E. Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase a2-iia. Proc Natl Acad Sci U S A. 2015; 112: E3564-73. Rowley JW, Chappaz S, Corduan A, Chong MM, Campbell R, Khoury A, Manne BK, Wurtzel JG, Michael JV, Goldfinger LE, Mumaw MM, Nieman MT, Kile BT, Provost P, Weyrich AS. Dicer1 mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood. 2016; 127: 1743-51. Osman A, Hitzler WE, Ameur A, Provost P. Differential expression analysis by RNA-seq reveals perturbations in the platelet mRNA transcriptome triggered by pathogen reduction systems. PLoS One. 2015; 10: e0133070. Osman A, Hitzler WE, Meyer CU, Landry P, Corduan A, Laffont B, Boilard E, Hellstern P, Vamvakas EC, Provost P. Effects of pathogen reduction systems on platelet microRNAs, mRNAs, activation, and function. Platelets. 2015; 26: 154-63. Ypma PF, van der Meer PF, Heddle NM, van Hilten JA, Stijnen T, Middelburg RA, Hervig T, van der Bom JG, Brand A, Kerkhoffs JL. A study protocol for a randomised controlled trial evaluating clinical effects of platelet transfusion products: The pathogen reduction evaluation and predictive analytical rating score (prepares) trial. BMJ Open. 2016; 6: e010156. Ivetic N, Nazi I, Karim N, Clare R, Smith JW, Moore JC, Hope KJ, Kelton JG, Arnold DM. Producing megakaryocytes from a human peripheral blood source. Transfusion. 2016. Zeller MP, Heddle NM, Kelton JG, Hamilton K, Wang G, Sholapur N, Carruthers J, Hsia C, Blais N, Toltl L, Hamm C, Pearson M-A, Arnold DM. Effect of a thrombopoietin receptor agonist on use of intravenous immune globulin in patients with immune thrombocytopenia. Transfusion. 2015. Xu M, Ma L, Carrim N, Yougbare I, Li J, Chen P, Zhu G, Ni H. Platelet GPIba is important for thrombopoietin production and thrombopoietin-induced platelet generation. Blood. 2015; 126: 12. Sheffield WP, Bhakta V, Jenkins C. Stability of coagulation protein activities in single units or pools of cryoprecipitate during storage at 20–24°C for up to 24 h. Vox Sang. 2016; 110: 12-9. Li J, van der Wal DE, Zhu G, Xu M, Yougbare I, Ma L, Vadasz B, Carrim N, Grozovsky R, Ruan M, Zhu L, Zeng Q, Tao L, Zhai Z-m, Peng J, Hou M, Leytin V, Freedman J, Hoffmeister KM, Ni H. Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia. Nat Commun. 2015; 6: 7737. Ma L, Simpson E, Li J, Xuan M, Xu M, Baker L, Shi Y, Yougbaré I, Wang X, Zhu G, Chen P, Prud’homme GJ, Lazarus AH, Freedman J, Ni H. CD8+ t cells are predominantly protective and required for effective steroid therapy in murine models of immune thrombocytopenia. Blood. 2015; 126: 247-56. Jansen AJG, Peng J, Zhao H-G, Hou M, Ni H. Sialidase inhibition to increase platelet counts: A new treatment option for thrombocytopenia. Am J Hematol. 2015; 90: E94-E5. Yougbaré I, Lang S, Yang H, Chen P, Zhao X, Tai W-S, Zdravic D, Vadasz B, Li C, Piran S, Marshall A, Zhu G, Tiller H, Killie MK, Boyd S, Leong-Poi H, Wen X-Y, Skogen B, Adamson SL, Freedman J, Ni H. Maternal anti-platelet β3 integrins impair angiogenesis and cause intracranial hemorrhage. J Clin Invest. 2015; 125: 1545-56. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 30 71. 72. 73. 74. 75. 76. 77. 78. 79. 80. 81. 82. 83. 84. 85. 86. 87. 88. 89. Ni H. ResearchUnit: Platelets vs. Blood vessels: What causes bleeding fetuses and newborns with fnait? Transfusionmedicineca website. 2015. Bernardo L, Yu H, Amash A, Zimring JC, Lazarus AH. IgG-mediated immune suppression to erythrocytes by polyclonal antibodies can occur in the absence of activating or inhibitory Fcγ receptors in a full mouse model. J Immunol. 2015; 195: 2224-30. Yu X, Menard M, Seabright G, Crispin M, Lazarus AH. A monoclonal antibody with anti-D– like activity in murine immune thrombocytopenia requires Fc domain function for immune thrombocytopenia ameliorative effects. Transfusion. 2015; 55: 1501-11. Lazarus A. ResearchUnit: Single site solution: Engineering novel antibodies for the treatment of ITP. Transfusionmedicineca website. 2015. Yu X, Menard M, Prechl J, Bhakta V, Sheffield WP, Lazarus AH. Monovalent Fc receptor blockade by an anti–Fcγ receptor/albumin fusion protein ameliorates murine ITP with abrogated toxicity. Blood. 2016; 127: 132-8. Amash A, Wang L, Wang Y, Bhakta V, Fairn GD, Hou M, Peng J, Sheffield WP, Lazarus AH. CD44 antibody inhibition of macrophage phagocytosis targets Fcγ receptor– and complement receptor 3–dependent mechanisms. J Immunol. 2016; 196: 3331-40. Pendergrast J, Willie-Ramharack K, Sampson L, Laroche V, Branch DR. The role of inflammation in intravenous immune globulin–mediated hemolysis. Transfusion. 2015; 55: S65S73. Guo L, Kapur R, Aslam R, Speck ER, Zufferey A, Zhao Y, Kim M, Lazarus AH, Ni H, Semple JW. CD20+ b-cell depletion therapy suppresses murine CD8+ t-cell-mediated immune thrombocytopenia. Blood. 2016; 127: 735-8. Kyluik-Price DL, Scott MD. Effects of methoxypoly (ethylene glycol) mediated immunocamouflage on leukocyte surface marker detection, cell conjugation, activation and alloproliferation. Biomaterials. 2016; 74: 167-77. Wang D, Shanina I, Toyofuku WM, Horwitz MS, Scott MD. Inhibition of autoimmune diabetes in nod mice by miRNA therapy. PLoS One. 2015; 10: e0145179. Abu-Khader A, Bugnot G, Alsheikh M, Pasha R, Pineault N. Conditioned medium represents a useful solution to increase the expansion of multipotent progenitors with strong platelet engraftment activity. Blood. 2015; 126: 4276. Toews M, Caulfield T, Nelson E, Ogbogu U, Hartell D. Rights and interests in human bodies and biological materials. Canadian National Transplant Research Program Fast Policy Facts: Human Bodies and Biological Materials. 2015. Walsh GM, Shih AW, Solh Z, Golder M, Schubert P, Fearon M, Sheffield WP. Blood-borne pathogens: A Canadian Blood Services centre for innovation symposium. Transfus Med Rev. 2016; 30: 53-68. Goldman M, Scalia V, Devine D. Donor selection, transmissible disease testing and pathogen reduction. In Clinical Guide to Transfusion. Edited by Clarke G, Chargé S. Published in transfusionmedicine.ca by Canadian Blood Services, 2015. Nahirniak S. Albumin. In Clinical Guide to Transfusion. Edited by Clarke G, Chargé S. Published in transfusionmedicine.ca by Canadian Blood Services, 2015. Poon MC, Goodyear MD, Lee A. Hemostatic disorders. In Clinical Guide to Transfusion. Edited by Clarke G, Chargé S. Published in transfusionmedicine.ca by Canadian Blood Services, 2015. Poon MC, Goodyear MD, Lee A. Coagulation factor concentrates. In Clinical Guide to Transfusion. Edited by Clarke G, Chargé S. Published in transfusionmedicine.ca by Canadian Blood Services, 2015. Goldman M, Hannaford K, Hannon J, Berardi P. Molecular immunohematology at canadian blood services: Red cell antigen genotyping. Transfusionmedicine.ca website. 2016. Ni H. ResearchUnit: Novel discovery reveals new diagnostic markers and treatment targets for bleeding disorder. Transfusionmedicine.ca website. 2015. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 31 90. 91. 92. Walsh G, Chargé S. Researchunits: Development and evaluation of a knowledge mobilization tool for transfusion medicine research. Canadian Society for Transfusion Medicine Website. 2015. O'Brien SF, Delage G, Scalia V, Lindsay R, Bernier F, Dubuc S, Germain M, Pilot G, Yi Q-L, Fearon MA. Seroprevalence of Babesia microti infection in Canadian blood donors. Transfusion. 2016; 56: 237-43. O'Brien S, Fearon M, Nahirniak S, Scalia V, Preiksaitis J. Prevalence and incidence of cytomegalovirus in blood donors and transplant patients. Canadian Society for Transfusion Medicine Website. 2015. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 32 Appendix I: Funded projects Summary of funded research project by program Projects receiving funding in fiscal year 2015-2016 Total: 160 Research program 55 Canadian Blood Services/CIHR partnership operating grants Blood utilization and conservation (20) Transfusion-related acute lung injury (3) Blood supply risk (3) 26 Canadian Blood Services/CIHR partnership new investigator awards 2 Intramural operating grants 9 Small projects funding 7 James Kreppner fellowships 2 Kenneth J. Fyke award 1 CIHR partnership: Transplantation research 1 Supplementary funding 7 Product and Process Development program Deepening the understanding of our products and the processes used to manufacture them 54 17 Developing new or next generation products and the processes used to develop them 12 Improving current generation products and the processes used to manufacture them 15 Enabling the product and process development group 4 Other 6 National training program 48 Transfusion medicine fellowships 3 Post-doctoral fellowships 10 Graduate fellowships 20 Summer internships 10 BloodTechNet awards 5 Program Support Award for Canadian Transfusion Medicine and Science Research Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 3 i Titles of projects funded by Research program Note: Projects that are italicized are those for which funding was initiated in fiscal year 2015–2016. Canadian Blood Services/CIHR Partnership National Operating Grant Program Purpose: Blood utilization and conservation The use of antibody-mediated immune suppression as a model in the development of a replacement for RhD prophylaxis in haemolytic disease of the fetus and newborn Improving the cryostorage of blood products using novel small molecule cryoprotectants Small molecule inhibitors of phagocytosis as replacement therapy for IVIg Development of novel blood vessel and organ sealants for blood conservation in surgical practice Platelet microRNAs during storage under blood bank conditions Transfusion of red cells in hematopoietic stem cell transplantation: the TRIST study Tranexamic acid versus placebo to reduce perioperative blood transfusion in patients undergoing major liver resection: a pilot randomized controlled trial Understanding host mechanisms responsible for immune platelet destruction and thrombocytopenia Polyhemoglobin catalase superoxide dismutase carbonic anhydrase: a novel soluble biotherapeutic with no cardiac toxicity for hemorrhagic shock and other uses Characterization of the hematopoietic reconstitution enhancing activity of osteoblasts derived from human mesenchymal stromal cells Design and implementation of circulatory oxygen therapeutics derived from human hemoglobin by improved systematic chemical coupling and cross-linking Release, delivery and cell programming effects of platelet microparticles and microRNAs Microfluidic devices to measure the deformability of stored red blood cells Understanding transcriptional and epigenetic control by Gfi1b towards the development of a therapy for sickle cell disease Pathogenesis and treatment of immune thrombocytopenia: are there fundamental differences between antiGPIba- and anti-GPllbllla-mediated thrombocytopenia? Defining disease mechanisms in immune thrombocytopenia (ITP) and their association with clinical outcomes Examining the relationship between repeated blood donations in female donors on maternal/neonatal outcomes: a cohort study Polymer-based manufacturing tolerogenic miRNA-based therapeutics Aneurysmal subarachnoid hemorrhage - red blood cell transfusion and outcome (SAHaRA): a pilot randomized controlled trial Myocardial ischemia and transfusion. The MINT rollover trial Purpose: Transfusion-related acute lung injury Mechanisms of antibody-independent transfusion-related acute lung injury (TRALI) Identification of host cellular immune mechanisms responsible for the initiation and/or modulation of transfusion related acute lung injury (TRALI) Transfusion-related acute lung injury and delayed TRALI: a prospective study in critically ill children Purpose: Blood supply risk Transfusion-related Epstein-Barr virus (EBV) infection among allogeneic stem cell transplant pediatric recipients: a multicenter prospective cohort study Short and long-term clinical effects of blood donor characteristics in transfusion recipients Exploratory analyses to determine if method of donor blood processing affects outcome in transfused recipients Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 ii Canadian Blood Services/CIHR Partnership New Investigator Program Transfusion requirements in cardiac surgery II (TRICS II) Code sepsis: defining and translating optimal resuscitation and care for children with septic shock Intramural Operating Grant Program Quality of transfusable plasma: mouse models and clinical samples Stealth erythrocytes: from bench to bedside Mechanism of action of intravenous immunoglobulin (IVIg): role of dendritic cells in stimulating T regulatory cells Antibodies to CD44 as a potential replacement for IVIg in ITP Residual risk of transfusion-transmitted cytomegalovirus infection: incidence and pathogenesis Defining the components of transfusable plasma that reduce bleeding Elucidation of the mechanism of IVIg-associated hemolysis Role of blood component manufacturing on microvesicle-induced transfusion-related immune modulation Monoclonal antibodies with anti-D-like activity in the amelioration of murine immune thrombocytopenia (ITP) Small Projects Funding Program Use of platelet transfusions in medical-surgical critically ill patients Understanding brain death: a multipurpose educational video aimed to a diverse public and professional audience Retrospective analysis of clinical outcomes in neonatal alloimmune thrombocytopenia (NAIT) related to antiHPA-1a Incidence of intracranial hemorrhage in pediatric oncology patients Red cell genotyping using buccal swab DNA Pre-transfusion furosemide for TACO ROTEM-guided transfusion protocols – impact on the manufacturer James Kreppner Fellowship in Blood System Studies Legal and policy strategies to optimize organ donation in Alberta Organ donation in Canada: engaging with stakeholders and proposing solutions to current legal and ethical challenges Kenneth J. Fyke Award Program Prospective observational study of organ deceased donor management in three ICUs – a pilot study (the DONATE pilot study) Supplementary Funding Program Purpose: External grant top-up CIHR: Polymer-grafted allogenic leukocytes and systemic immune modulation Heart & Stroke Foundation: Auxiliary cofactors in fibrinolysis Burroughs Wellcome Fund: Innovation in regulatory science CIHR: Pathogenesis of fetal and neonatal alloimmune thrombocytopenia and IVIg anti-FcRn therapies Purpose: Bridge funding Small molecule inhibitors of phagocytosis as replacement therapy for IVIg Impact of cord blood processing delay on the loss of engraftment activity and on the release of microparticles Understanding the physiological mechanisms responsible for the predominance of staphylococcus epidermidis as a platelet contaminant — a genomic approach Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 iii Titles of projects conducted by Product and Process Development program Deepening the understanding of our products and the processes used to manufacture them Bacterial growth in red blood cells prepared in different additive solutions (derived from the 30-minute rule) BEST 74 – irradiation study BEST 83 – hemolysis standardization Comparison of bacterial attachment between apheresis and buffy coat platelet bags Cryopreservation of Gerbich/Leach donor Exploratory analyses to determine if method of donor blood processing affects outcome in transfused recipients Frozen red blood cell products international standardization Impact of cord blood to anticoagulant ratios on hematopoietic stem cells Impact of donor sex, age and hemoglobin status on hemolysis Impact of donor variation on platelet quality Platelet aggregate issue Product characterization – quality monitoring program for 2015-16 Product characterization – quality monitoring program for cord blood derived hematopoietic stem cells Quality assessment of cryopreserved/irradiated CPD/SAGM red blood cell units Short and long-term clinical effects of blood donor characteristics in transfusion recipients The effects of room temperature exposure on plasma (30 minute rule) The effects of room temperature exposure on red blood cell units (30 minute rule) Developing new or next generation products and the processes used to manufacture them ACP-215 cell processor implementation (washed red blood cells) ACP-215 closed system cryopreservation White paper: current state of 7-day platelets Development of cord blood unit thawing protocol Environmental scan: freeze dried (lyophilized) plasma Environmental scan: platelet additive solutions Evaluation of the efficacy of the Mirasol® pathogen reduction technology system to eradicate biofilmforming bacteria Evaluation of the efficacy of the Mirasol® pathogen reduction technology system to eradicate low bacteria titres in buffy coat platelet pools at different irradiation times Haemonetics Solx/ Fenwal ESol ACP-215 study INTERCEPT (Cerus) pathogen inactivation system MIRASOL (Terumo) pathogen inactivation system THERAFLEX (Macopharma) pathogen inactivation system Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 iv Improving current generation products and the processes used to manufacture them Bacterial growth during storage of thawed cryoprecipitate at 20-24°C for 24 hours Cold versus warm evaluation Contingency 'blood bags' - B2 production Data review for future use of one pack type with no cooling trays Elimination of cooling trays Evaluation of alternative skin disinfection kits for donors allergic to chlorhexidine Evaluation of the ADAM instrument for residual white blood cell testing Exploration of options to test cord blood units that contain antibiotics for bacterial contamination Investigation of leukoreduction effectiveness in b2 whole blood with incomplete filtration Modeling unit volumes after non-destructive testing Non-destructive quality control testing for platelet products Non-destructive quality control testing for red blood cell products Production equipment process cycle time optimization: CompoMat Rinse modification to the platelet pooling process Support validation of CompoLab instrument Enabling the product and process development group Increasing netCAD testing capabilities NetCAD4cord Product and process development (PPD) test method validation: standardization and qualification of test assays in centre for innovation labs supporting PPD group projects Product characterization – quality monitoring program database Other Alberta inventory and logistics Canadian Blood Services clinic simulator Evaluating the efficacy of skin disinfectants when combined with natural oils Holiday platelet planner Hospital ordering behaviour and management of O-negative inventory Modeling and simulation education and training Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 v Titles of projects funded by National Training Program Note: Projects that are italicized are those for which funding was initiated in fiscal year 2015–2016. Post-Doctoral Fellowship Program Pathogenesis of fetal and neonatal alloimmune thrombocytopenia and mechanisms of IVIg therapy Study of the apoptosis mechanism in blood processing and platelet storage in order to improve stored platelet quality after pathogen inactivation treatment CD8+CD25+ regulatory T cells: unveiling new mechanisms and treatment of ITP Role of Fc receptors in antibody-mediated immune suppression Transfusion options in coagulopathy: efficacy in controlling bleeding Understanding IVIg mechanism(s) of action in alleviating immune platelet destruction and thrombocytopenia Understanding the factors that influence bacterial proliferation and biofilm formation in platelet concentrates Mechanism of anti-D-like antibody-mediated amelioration of immune thrombocytopenia (ITP) Novel mechanism of phagocytosis and cytopenia: exploring the role of integrin thiol isomerase activity in immunosynapse formation and alternative therapy for ITP DNA aptamers for detection of red blood cells destined for rapid post-transfusion clearance Graduate Fellowship Program The in vivo effects of liposome treatment on minimizing membrane injury in rat red blood cells during hypothermic storage Identification of protein biomarkers for red cell quality MRI-guided focused ultrasound facilitated IVIg immunotherapy as a therapeutic approach for Alzheimer's disease Application of microfluidic technology to blood group genotyping for non-invasive prenatal diagnosis of fetal RhD status Relationship of warm autoimmune hemolytic anemia to normal red cell senescence Assessment of fluorinated ice crystallization inhibitors; cryopreservation of hematopoietic stem cells and red blood cells Characterization of the role of Msi2 in human hematopoietic stem cell self-renewal Role of skin disinfection and buffy coat platelet production on residual bacterial contamination in platelet concentrates and cord blood stem cells Novel mechanisms of plasma fibronectin in hemostasis, cryoprecipitate therapy and platelet storage: potential applications in transfusion medicine Mechanism of transplacental transport of IgGs, and IVIg and anti-FcRn therapies in the treatment of fetal and neonatal alloimmune thrombocytopenia Study of the role of platelet microRNAs Studies on the development of biocompatible antimicrobial platelet storage devices Towards the impact of protein synthesis in human platelets to transfusion medicine Investigation of pathophysiology, prevention and treatment of murine transfusion related acute lung injury (TRALI) Cellular therapy to improve CD4+ T-cell responses in humanized mice infected with HIV-1: adoptive transfer of CD4+ T-cells lacking s-Src activity Impact of storage on the function of cord blood hematopoietic stem and progenitor cells Small molecule inhibitors of phagocytosis to replace intravenous immunoglobulin (IVIg) Dengue virus replication by anucleate cells: impact on pathogen reduction efficacy Recombinant Fc multimers to replace IVIg Study of the mechanisms implicated in platelet microparticle internalization by blood cells Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 vi Summer Internship Program Investigation of apheresis platelet concentrates from donors with repeat low pH measurements The role of mononuclear cells in modulating neutrophil activation in antibody-mediated TRALI Investigation of the mean of action of osteoblasts on hematopoietic stem and progenitor cells expansion Improving the cryopreservation of a cord red blood cell product by controlling ice growth with small molecule ice recrystallization inhibitors Donor selection and optimal source of cells for allogeneic hematopoietic transplantation: a network metaanalysis Strengthening the quality and quantity of membership on Canada’s stem cell donor-database PCC, aPCC, and rFVIIa for novel oral anticoagulant associated major bleeding Setting the benchmark metric for red blood cell transfusion: a quality project Characteristics of the biofilm matrix and its role in the survival and growth of Staphylococcus epidermidis during platelet storage Exploration of an IVIG utilization oversight model from existing frameworks BloodTechNet Award Program Better blood transfusion: neonatal and pediatric patients Blood Matters 2014 Transfusion confusion: an interprofessional online learning module Snippets at the time of need: transfusion medicine ePerformance support tools The Stem Cell Club: educating medical students about stem cell transplantation Titles of projects funded by Program Support Award for Canadian Transfusion Medicine and Science Research McMaster Transfusion Research Program University of Ottawa Centre for Transfusion Research Centre for Blood Research Infrastructure Support for Transfusion Research Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 vii Appendix II: Publications Summary of peer-reviewed and non-peer-reviewed publications from fiscal year 2015-2016 # of peer-reviewed and non-peer-reviewed publications in fiscal year 2015-16 355 Peer-Reviewed Publications 317 Journal Articles 122 Review Articles 22 Comments/Letters/Editorials 11 Books/Book Sections 1 Published Abstracts 157 Canadian Blood Services Circular of Information 4 38 Non-Peer-Reviewed Publications CBS Website Publications 13 Fast policy facts 1 Technical Reports 23 Theses 1 Summary of h-index factor analysis 50 H-Index 40 30 H-Index 20 H-Index (past 5 years) 10 Mean H-Index Mean H-Index (past 5 years) 0 A B C D F G H I J K L M N O Investigator P Notes: i) H‐Index factors measured using GoogleScholar on April 5 2016. ii) Mean H‐ index calculated using H‐Index factors from the 15 core investigators. Core investigators include (Jason Acker, John Blake, Donald Branch, Dana Devine, Margaret Fearon, Mindy Goldman, Alan Lazarus, Heyu Ni, Sheila O’Brien, Nicolas Pineault, Ed Pryzdial, Sandra Ramirez-Arcos, Mark Scott, William Sheffield, and Kathryn Webert). iii) H‐Index is a single bibliometric indicator that is a measure of both the productivity and impact of published work. H‐Index is an indicator of research users being aware of and valuing published research evidence. Average H-index for Canadian university professors in the biological sciences is 10.6. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 viii Publications’ Details Author Legend: Bold – Centre for Innovation investigators and senior staff; Canadian Blood Services medical directors; Directors of transfusion medicine research programs receiving funding via the Program Support Award for Transfusion Medicine and Science Research. Underlined – Non-Canadian Blood Services investigators funded in part by Canadian Blood Services. Journal Articles 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. Abdelbaset-Ismail A, Borkowska S, Janowska-Wieczorek A, Tonn T, Rodriguez C, Moniuszko M, Bolkun L, Koloczko J, Eljaszewicz A, Ratajczak J, Ratajczak MZ, Kucia M. Novel evidence that pituitary gonadotropins directly stimulate human leukemic cells-studies of myeloid cell lines and primary patient AML and CML cells. Oncotarget. 2015; 7: 3033-3046. Acker JP, Hansen AL, Yi Q-L, Sondi N, Cserti-Gazdewich C, Pendergrast J, Hannach B. Introduction of a closed-system cell processor for red blood cell washing: Postimplementation monitoring of safety and efficacy. Transfusion. 2016; 56: 49-57. Alexander PE, Barty R, Fei Y, Vandvik PO, Pai M, Siemieniuk RA, Heddle NM, Blumberg N, McLeod SL, Liu J, Eikelboom JW, Guyatt GH. Transfusion of fresher vs older red blood cells in hospitalized patients: A systematic review and meta-analysis. Blood. 2016; 127: 400-410. Allan DS, Scrivens N, Lawless T, Mostert K, Oppenheimer L, Walker M, Petraszko T, Elmoazzen H. Delayed clamping of the umbilical cord after delivery and implications for public cord blood banking. Transfusion. 2015. Alwasaidi TA, Hamadah A, Altouri S, Tay J, McDiarmid S, Faught C, Allan D, Huebsch L, Bredeson C, Bence-Bruckler I. Outcomes of both abbreviated hyper-CVAD induction followed by autologous hematopoietic cell transplantation and conventional chemotherapy for mantle cell lymphoma: A 10-year single-centre experience with literature review. Cancer Med. 2015; 4: 18171827. Amash A, Wang L, Wang Y, Bhakta V, Fairn GD, Hou M, Peng J, Sheffield WP, Lazarus AH. CD44 antibody inhibition of macrophage phagocytosis targets Fcγ receptor– and complement receptor 3–dependent mechanisms. J Immunol. 2016; 196: 3331-3340. Atkins CG, Buckley K, Chen D, Schulze HG, Devine DV, Blades MW, Turner RFB. Raman spectroscopy of stored red blood cells: Evaluating clinically-relevant biochemical markers in donated blood. Clinical and Biomedical Spectroscopy and Imaging IV. 2015; 9537: 95370X. Bakkour S, Acker JP, Chafets DM, Inglis HC, Norris PJ, Lee TH, Busch MP. Manufacturing method affects mitochondrial DNA release and extracellular vesicle composition in stored red blood cells. Vox Sang. 2016. Bernardo L, Yu H, Amash A, Zimring JC, Lazarus AH. IgG-mediated immune suppression to erythrocytes by polyclonal antibodies can occur in the absence of activating or inhibitory Fcγ receptors in a full mouse model. J Immunol. 2015; 195: 2224-2230. Bian Y, Guo C, Chang T. Temperature stability of poly-[hemoglobin-superoxide dismutase-catalasecarbonic anhydrase] in the form of a solution or in the lyophilized form during storage at −80°C, 4°C, 25°C and 37°C or pasteurization at 70°C. Artif Cells Nanomed Biotechnol. 2016; 44: 41-47. Bicalho B, Pereira AS, Acker JP. Buffy coat (top/bottom)- and whole-blood filtration (top/top)produced red cell concentrates differ in size of extracellular vesicles. Vox Sang. 2015; 109: 214-220. Bicalho B, Serrano K, dos Santos Pereira A, Devine D, Acker J. Blood bag plasticizers influence red blood cell vesiculation rate without altering the lipid composition of the vesicles. Transfus Med Hemother. 2015. Branch DR. Anti-A and anti-B: What are they and where do they come from? Transfusion. 2015; 55: S74-S79. Briard JG, Poisson JS, Turner TR, Capicciotti CJ, Acker JP, Ben RN. Small molecule ice recrystallization inhibitors mitigate red blood cell lysis during freezing, transient warming and thawing. Sci Rep. 2016; 6: 23619. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 ix 15. Buckley K, Atkins CG, Chen D, Schulze HG, Devine DV, Blades MW, Turner RFB. Non-invasive spectroscopy of transfusable red blood cells stored inside sealed plastic blood-bags. Analyst. 2016; 141: 1678-1685. 16. Burger D, Viñas JL, Akbari S, Dehak H, Knoll W, Gutsol A, Carter A, Touyz RM, Allan DS, Burns KD. Human endothelial colony-forming cells protect against acute kidney injury: Role of exosomes. Am J Pathol. 2015; 185: 2309-2323. 17. Byrnes JR, Duval C, Wang Y, Hansen CE, Ahn B, Mooberry MJ, Clark MA, Johnsen JM, Lord ST, Lam WA, Meijers JCM, Ni H, Ariëns RAS, Wolberg AS. Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking. Blood. 2015; 126: 1940-1948. 18. Cameron-Vendrig A, Reheman A, Siraj MA, Xu XR, Wang Y, Lei X, Afroze T, Shikatani E, ElMounayri O, Noyan H, Weissleder R, Ni H, Husain M. Glucagon-like peptide-1 receptor activation attenuates platelet aggregation and thrombosis. Diabetes. 2016. 19. Capicciotti CJ, Kurach JDR, Turner TR, Mancini RS, Acker JP, Ben RN. Small molecule ice recrystallization inhibitors enable freezing of human red blood cells with reduced glycerol concentrations. Sci Rep. 2015; 5. 20. Cembrowski G, Topping K, Versluys K, Tran D, Malick M, Holmes D, Clarke G. The use of serial outpatient complete blood count (CBC) results to derive biologic variation: A new tool to gauge the acceptability of hematology testing. Int J Lab Hematol. 2015. 21. Chai-Adisaksopha C, Hillis C, Isayama T, Lim W, Iorio A, Crowther M. Mortality outcomes in patients receiving direct oral anticoagulants: A systematic review and meta-analysis of randomized controlled trials. J Thromb Haemost. 2015; 13: 2012-2020. 22. Chai-Adisaksopha C, Hillis C, Lim W, Boonyawat K, Moffat K, Crowther M. Hemodialysis for the treatment of dabigatran-associated bleeding: A case report and systematic review. J Thromb Haemost. 2015; 13: 1790-1798. 23. Chai-Adisaksopha C, Hillis C, Monreal M, Witt DM, Crowther M. Thromboembolic events, recurrent bleeding and mortality after resuming anticoagulant following gastrointestinal bleeding. A meta-analysis. Thromb Haemost. 2015; 114: 819-825. 24. Chai-Adisaksopha C, Hillis C, Thabane L, Iorio A. A systematic review of definitions and reporting of bleeding outcome measures in haemophilia. Haemophilia. 2015; 21: 731-735. 25. Chai-Adisaksopha C, Lam W, Hillis C. Major arterial events in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors: A meta-analysis. Leuk Lymphoma. 2015: 1-11. 26. Chen Y, Ge J, Ruan M, Zhu L-Y, Zeng Q-S, Xia R-X, Ni H. [Influence of anticoagulants on detection of ITP platelet-specific autoantibodies and relationship of autoantibody types with glucocorticoid efficacy]. Zhongguo shi yan xue ye xue za zhi. 2015; 23: 1380-1385. 27. Ching JC, Lau W, Hannach B, Upton JE. Peanut and fish allergy due to platelet transfusion in a child. CMAJ. 2015; 187: 905-907. 28. Clark WF, Rock G, Barth D, Arnold DM, Webert KE, Yenson PR, Kelton JG, Li L, Foley SR, members of the Canadian Apheresis G. A phase-II sequential case-series study of all patients presenting to four plasma exchange centres with presumed relapsed/refractory thrombotic thrombocytopenic purpura treated with rituximab. Br J Haematol. 2015; 170: 208-217. 29. Deng X, Duffy SP, Myrand-Lapierre M-E, Matthews K, Santoso AT, Du Y-L, Ryan KS, Ma H. Reduced deformability of parasitized red blood cells as a biomarker for anti-malarial drug efficacy. Malar J. 2015; 14: 428. 30. Duchez AC, Boudreau LH, Naika GS, Bollinger J, Belleannee C, Cloutier N, Laffont B, MendozaVillarroel RE, Levesque T, Rollet-Labelle E, Rousseau M, Allaeys I, Tremblay JJ, Poubelle PE, Lambeau G, Pouliot M, Provost P, Soulet D, Gelb MH, Boilard E. Platelet microparticles are internalized in neutrophils via the concerted activity of 12-lipoxygenase and secreted phospholipase A2-IIA. Proc Natl Acad Sci U S A. 2015; 112: E3564-3573. 31. Dzandzi JPK, Beckford Vera DR, Genady AR, Albu SA, Eltringham-Smith LJ, Capretta A, Sheffield WP, Valliant JF. Fluorous analogue of chloramine-T: Preparation, x-ray structure Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 x 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. determination, and use as an oxidant for radioiodination and s-tetrazine synthesis. J Org Chem. 2015; 80: 7117-7125. Elboraee MS, Clarke G, Belletrutti MJ, Escoredo S. HbM methaemoglobinaemia as a rare case of early neonatal benign cyanosis. BMJ Case Reports. 2015; 2015. Elgheznawy A, Shi L, Hu J, Wittig I, Laban H, Pircher J, Mann A, Provost P, Randriamboavonjy V, Fleming I. Dicer cleavage by calpain determines platelet microRNA levels and function in diabetes. Circ Res. 2015; 117: 157-165. English SW, Chassé M, Turgeon AF, Tinmouth A, Boutin A, Pagliarello G, Fergusson D, McIntyre L. Red blood cell transfusion and mortality effect in aneurysmal subarachnoid hemorrhage: A systematic review and meta-analysis protocol. Syst Rev. 2015; 4: 41. Fedorov K, Jankowski A, Sheikh S, Blaszykowski C, Reheman A, Romaschin A, Ni H, Thompson M. Prevention of surface-induced thrombogenesis on poly(vinyl chloride). J Mater Chem B Mater Biol Med. 2015. Gierczak RF, Bhakta V, Xie M, Sheffield WP. Comparison of mammalian and bacterial expression library screening to detect recombinant alpha-1 proteinase inhibitor variants with enhanced thrombin inhibitory capacity☆. J Biotechnol. 2015; 208: 54-62. Goldman M, Cemborain A, Cote J, El Hamss R, Flower RL, Garaizar A, Garcia-Sanchez F, Hyland CA, Kalvelage M, Londero D, Lopez GH, Revelli N, Rodriguez-Wilhelmi P, Villa A, Ochoa-Garay G. Identification of six new RHCE variant alleles in individuals of diverse racial origin. Transfusion. 2016; 56: 244-248. Goldman M, Land K, Robillard P, Wiersum-Osselton J. Development of standard definitions for surveillance of complications related to blood donation. Vox Sang. 2016; 110: 185-188. Goldman M, Lane D, Webert K, Fallis R. The prevalence of anti-K in Canadian prenatal patients. Transfusion. 2015; 55: 1486-1491. Gray N, Newbold KB, Lane SJ, Heddle NM, Webert K, Eyles J. Public perceptions of pathogen reduction technology in the Canadian donor blood supply. ISBT Sci Ser. 2015. Guo C, Gynn M, Chang T. Extraction of superoxide dismutase, catalase, and carbonic anhydrase from stroma-free red blood cell hemolysate for the preparation of the nanobiotechnological complex of polyhemoglobin–superoxide dismutase–catalase–carbonic anhydrase. Artif Cells Nanomed Biotechnol. 2015; 43: 157-162. Guo L, Kapur R, Aslam R, Speck ER, Zufferey A, Zhao Y, Kim M, Lazarus AH, Ni H, Semple JW. CD20+ B-cell depletion therapy suppresses murine CD8+ T-cell-mediated immune thrombocytopenia. Blood. 2016; 127: 735-738. Guo Q, Duffy SP, Matthews K, Deng X, Santoso AT, Islamzada E, Ma H. Deformability based sorting of red blood cells improves diagnostic sensitivity for malaria caused by plasmodium falciparum. Lab Chip. 2016; 16: 645-654. Hansen AL, Turner TR, Kurach JDR, Acker JP. Quality of red blood cells washed using a second wash sequence on an automated cell processor. Transfusion. 2015. Heddle NM, Arnold DM, Acker JP, Liu Y, Barty RL, Eikelboom JW, Webert KE, Hsia CC, O'Brien SF, Cook RJ. Red blood cell processing methods and in-hospital mortality: A transfusion registry cohort study. Lancet Haematol. 2016. Hubert A, Subra C, Jenabian MA, Tremblay Labrecque PF, Tremblay C, Laffont B, Provost P, Routy JP, Gilbert C. Elevated abundance, size, and MicroRNA content of plasma extracellular vesicles in viremic HIV-1+ patients: Correlations with known markers of disease progression. J Acquir Immune Defic Syndr. 2015; 70: 219-227. Hun Yeon J, Chan KYT, Wong T-C, Chan K, Sutherland MR, Ismagilov RF, Pryzdial ELG, Kastrup CJ. A biochemical network can control formation of a synthetic material by sensing numerous specific stimuli. Sci Rep. 2015; 5: 10274. Ivetic N, Nazi I, Karim N, Clare R, Smith JW, Moore JC, Hope KJ, Kelton JG, Arnold DM. Producing megakaryocytes from a human peripheral blood source. Transfusion. 2016. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xi 49. Jaffer AM, Wang G, Barty RL, Shih AW. Evaluation of CONSORT compliance in transfusion. Transfusion. 2015. 50. 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. 51. Jordan A, Acker J. Determining the volume of additive solution and residual plasma in whole blood filtered and buffy coat processed red cell concentrates. Transfus Med Hemother. 2015. 52. Jordan A, Chen D, Yi QL, Kanias T, Gladwin MT, Acker JP. Assessing the influence of component processing and donor characteristics on quality of red cell concentrates using quality control data. Vox Sang. 2016. 53. Kapur R, Kim M, Shanmugabhavananthan S, Liu J, Li Y, Semple JW. C-reactive protein enhances murine antibody–mediated transfusion-related acute lung injury. Blood. 2015; 126: 2747-2751. 54. Kou Y, Pagotto F, Hannach B, Ramirez-Arcos S. Fatal false-negative transfusion infection involving a buffy coat platelet pool contaminated with biofilm-positive staphylococcus epidermidis: A case report. Transfusion. 2015. 55. Kwan DH, Constantinescu I, Chapanian R, Higgins MA, Kotzler MP, Samain E, Boraston AB, Kizhakkedathu JN, Withers SG. Toward efficient enzymes for the generation of universal blood through structure-guided directed evolution. J Am Chem Soc. 2015; 137: 5695-5705. 56. Kwan DH, Ernst S, Kotzler MP, Withers SG. Chemoenzymatic synthesis of a type 2 blood group a tetrasaccharide and development of high-throughput assays enables a platform for screening blood group antigen-cleaving enzymes. Glycobiology. 2015; 25: 806-811. 57. Kyluik-Price DL, Scott MD. Effects of methoxypoly (ethylene glycol) mediated immunocamouflage on leukocyte surface marker detection, cell conjugation, activation and alloproliferation. Biomaterials. 2016; 74: 167-177. 58. Lacroix J, Hébert PC, Fergusson DA, Tinmouth A, Walsh T, Stanworth S, Campbell H, Boyd J, Burrows H, Hemmatapour S, on behalf of the Canadian Critical Care Trials Group. A randomized controlled trial comparing the outcome of critically ill adults who received fresher vs. older red cells units. ISBT Sci Ser. 2016; 11: 332-336. 59. Laffont B, Corduan A, Rousseau M, Duchez AC, Lee CH, Boilard E, Provost P. Platelet microparticles reprogram macrophage gene expression and function. Thromb Haemost. 2016; 115: 311-323. 60. Lang E, Bissinger R, Fajol A, Salker MS, Singh Y, Zelenak C, Ghashghaeinia M, Gu S, Jilani K, Lupescu A, Reyskens KM, Ackermann TF, Foller M, Schleicher E, Sheffield WP, Arthur JS, Lang F, Qadri SM. Accelerated apoptotic death and in vivo turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2. Sci Rep. 2015; 5: 17316. 61. Leung VL, Kizhakkedathu JN. The mechanism and modulation of complement activation on polymer grafted cells. Acta Biomater. 2016; 31: 252-263. 62. Lewis JK, Bischof JC, Braslavsky I, Brockbank KGM, Fahy GM, Fuller BJ, Rabin Y, Tocchio A, Woods EJ, Wowk BG, Acker JP, Giwa S. The grand challenges of organ banking: Proceedings from the first global summit on complex tissue cryopreservation. Cryobiology. 2015. 63. Li J, van der Wal DE, Zhu G, Xu M, Yougbare I, Ma L, Vadasz B, Carrim N, Grozovsky R, Ruan M, Zhu L, Zeng Q, Tao L, Zhai Z-m, Peng J, Hou M, Leytin V, Freedman J, Hoffmeister KM, Ni H. Desialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia. Nat Commun. 2015; 6: 7737. 64. Li L, Noumsi GT, Kwok YYE, Moulds JM, Scott MD. Inhibition of phagocytic recognition of antiD opsonized Rh D+ RBC by polymer-mediated immunocamouflage. Am J Hematol. 2015; 90: 11651170. 65. Lin HX, Sjaarda J, Dyck J, Stringer R, Hillis C, Harvey M, Carter R, Ainsworth P, Leber B, Pare G, Sadikovic B. Gender and BCR-ABL transcript type are correlated with molecular response to imatinib treatment in patients with chronic myeloid leukemia. Eur J Haematol. 2016; 96: 360-366. 66. Lin Y, Tinmouth A, Mallick R, Haspel RL, for the BEST-TEST2 Investigators. BEST-TEST2: Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xii Assessment of hematology trainee knowledge of transfusion medicine. Transfusion. 2015. 67. Linkins LA, Bates SM, Lee AY, Heddle NM, Wang G, Warkentin TE. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: Prospective cohort study. Blood. 2015; 126: 597-603. 68. Loza-Correa M, Perkins H, Kumaran D, Kou Y, Qaisar R, Geelhood S, Ramirez-Arcos S. Noninvasive pH monitoring for bacterial detection in platelet concentrates. Transfusion. 2016. 69. Ma L, Simpson E, Li J, Xuan M, Xu M, Baker L, Shi Y, Yougbaré I, Wang X, Zhu G, Chen P, Prud’homme GJ, Lazarus AH, Freedman J, Ni H. CD8+ T cells are predominantly protective and required for effective steroid therapy in murine models of immune thrombocytopenia. Blood. 2015; 126: 247-256. 70. Malinowski AK, Shehata N, D’Souza R, Kuo KHM, Ward R, Shah PS, Murphy K. Prophylactic transfusion for pregnant women with sickle cell disease: A systematic review and meta-analysis. Blood. 2015; 126: 2424-2435. 71. Matthews K, Myrand-Lapierre M-E, Ang RR, Duffy SP, Scott MD, Ma H. Microfluidic deformability analysis of the red cell storage lesion. J Biomech. 2015; 48: 4065-4072. 72. McCarthy SDS, Majchrzak-Kita B, Racine T, Kozlowski HN, Baker DP, Hoenen T, Kobinger GP, Fish EN, Branch DR. A rapid screening assay identifies monotherapy with interferon-ß and combination therapies with nucleoside analogs as effective inhibitors of Ebola virus. PLoS Negl Trop Dis. 2016; 10: e0004364. 73. McCarthy SDS, Sakac D, Neschadim A, Branch DR. C-SRC protein tyrosine kinase regulates early HIV-1 infection post-entry. AIDS. 2016; 30: 849-858. 74. McVey MJ, Spring C, Semple JW, Maishan M, Kuebler WM. Microparticles as biomarkers of lung disease - enumeration in biological fluids using lipid bilayer microspheres. Am J Physiol Lung Cell Mol Physiol. 2016. 75. Molnar AO, Fergusson D, Tsampalieros AK, Bennett A, Fergusson N, Ramsay T, Knoll GA. Generic immunosuppression in solid organ transplantation: Systematic review and meta-analysis. BMJ. 2015; 350: h3163. 76. Morrison LJ, Gent LM, Lang E, Nunnally ME, Parker MJ, Callaway CW, Nadkarni VM, Fernandez AR, Billi JE, Egan JR, Griffin RE, Shuster M, Hazinski MF. Part 2: Evidence evaluation and management of conflicts of interest: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015; 132: S368382. 77. Nazi I, Arnold DM, Warkentin TE, Smith JW, Staibano P, Kelton JG. Distinguishing between anti– platelet factor 4/heparin antibodies that can and cannot cause heparin-induced thrombocytopenia. J Thromb Haemost. 2015; 13: 1900-1907. 78. O'Brien SF, Delage G, Scalia V, Lindsay R, Bernier F, Dubuc S, Germain M, Pilot G, Yi Q-L, Fearon MA. Seroprevalence of Babesia microti infection in Canadian blood donors. Transfusion. 2016; 56: 237-243. 79. O'Brien SF, Delage G, Seed CR, Pillonel J, Fabra CC, Davison K, Kitchen A, Steele WR, Leiby DA. The epidemiology of imported malaria and transfusion policy in five non-endemic countries. Transfus Med Rev. 2015; 29: 162-171. 80. O'Brien SF, Osmond L, Choquet K, Yi QL, Goldman M. Donor attention to reading materials. Vox Sang. 2015. 81. O'Brien SF, Osmond L, Fan W, Yi Q-L, Goldman M. Impact of a 5-year deferral from blood donation for men who have sex with men. Transfusion. 2015. 82. O'Brien SF, Osmond L, Yi Q-L. How do I interpret a p value? Transfusion. 2015; 55: 2778-2782. 83. Osman A, Hitzler WE, Ameur A, Provost P. Differential expression analysis by RNA-seq reveals perturbations in the platelet mRNA transcriptome triggered by pathogen reduction systems. PLoS One. 2015; 10: e0133070. 84. Pai M, Cook R, Barty R, Eikelboom J, Lee KA, Heddle N. Exposure to ABO-nonidentical blood Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xiii associated with increased in-hospital mortality in patients with group A blood. Transfusion. 2016; 56: 550-557. 85. Pendergrast J, Willie-Ramharack K, Sampson L, Laroche V, Branch DR. The role of inflammation in intravenous immune globulin–mediated hemolysis. Transfusion. 2015; 55: S65-S73. 86. Pereira Beak C, Chargé SB, Isasi R, Knoppers BM. Developing educational resources to advance umbilical cord blood banking and research: A Canadian perspective. J Obstet Gynaecol Can. 2015; 37: 443-450. 87. Petrik J, Lozano M, Seed CR, Faddy HM, Keller AJ, Prado Scuracchio PS, Wendel S, Andonov A, Fearon M, Delage G, Zhang J, Shih JWK, Gallian P, Djoudi R, Tiberghien P, Izopet J, Dreier J, Vollmer T, Knabbe C, Aggarwal R, Goel A, Ciccaglione AR, Matsubayashi K, Satake M, Tadokoro K, Jeong S-H, Zaaijer HL, Zhiburt E, Chay J, Teo D, Chua SS, Piron M, Sauleda S, Echevarría J-M, Dalton H, Stramer SL. Hepatitis E. Vox Sang. 2015. 88. Qadri SM, Donkor DA, Bhakta V, Eltringham-Smith LJ, Dwivedi DJ, Moore JC, Pepler L, Ivetic N, Nazi I, Fox-Robichaud AE, Liaw PC, Sheffield WP. Phosphatidylserine externalization and procoagulant activation of erythrocytes induced by Pseudomonas aeruginosa virulence factor pyocyanin. J Cell Mol Med. 2016; 20: 710-720. 89. Ramirez-Arcos S, Alport T, Goldman M. Intermittent bacteremia detected in an asymptomatic apheresis platelet donor with repeat positive culture for Escherichia coli: A case report. Transfusion. 2015; 55: 2606-2608. 90. Ratajczak MZ, Borkowska S, Mierzejewska K, Kucia M, Mendek-Czajkowska E, Suszynska M, Sharma VA, Deptala A, Song W, Platzbecker U, Larratt L, Janowska-Wieczorek A, Maciejewski J, Ratajczak J. Further evidence that paroxysmal nocturnal haemoglobinuria is a disorder of defective cell membrane lipid rafts. J Cell Mol Med. 2015; 19: 2193-2201. 91. Rowley JW, Chappaz S, Corduan A, Chong MM, Campbell R, Khoury A, Manne BK, Wurtzel JG, Michael JV, Goldfinger LE, Mumaw MM, Nieman MT, Kile BT, Provost P, Weyrich AS. Dicer1 mediated miRNA processing shapes the mRNA profile and function of murine platelets. Blood. 2016; 127: 1743-1751. 92. Santoso AT, Deng X, Lee J-H, Matthews K, Duffy SP, Islamzada E, McFaul SM, Myrand-Lapierre M-E, Ma H. Microfluidic cell-phoresis enabling high-throughput analysis of red blood cell deformability and biophysical screening of antimalarial drugs. Lab Chip. 2015; 15: 4451-4460. 93. Sarhangian V, Abouee-Mehrizi H, Baron O, Berman O, Heddle NM, Barty R. Reducing the age of transfused red blood cells in hospitals: Ordering and allocation policies. Vox Sang. 2016. 94. Schubert P, Coupland D, Nombalais M, Walsh G, Devine DV. RhoA/ROCK signaling contributes to sex differences in the activation of human platelets. Thrombosis Res. 2016; 139: 50-55. 95. Schulman S, Carrier M, Lee AY, Shivakumar S, Blostein M, Spencer FA, Solymoss S, Barty R, Wang G, Heddle N, Douketis JD. Perioperative management of dabigatran: A prospective cohort study. Circulation. 2015; 132: 167-173. 96. 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. 2015. 97. Sheffield WP, Bhakta V. The M358R variant of α1-proteinase inhibitor inhibits coagulation factor VIIa. Biochem Biophys Res Commun. 2016; 470: 710-713. 98. Sheffield WP, Bhakta V, Jenkins C. Stability of coagulation protein activities in single units or pools of cryoprecipitate during storage at 20–24°C for up to 24 h. Vox Sang. 2016; 110: 12-19. 99. Shehata N, Forster AJ, Lawrence N, Ducharme R, Fergusson DA, Chassé M, Rothwell DM, Hébert PC, Tinmouth AT, Wilson K. Transfusion patterns in all patients admitted to the intensive care unit and in those who die in hospital: A descriptive analysis. PLoS One. 2015; 10: e0138427. 100. Sheppard D, Tay J, Palmer D, Xenocostas A, Doulaverakis C, Huebsch L, McDiarmid S, Tinmouth A, Mallick R, Martin L, Birch P, Hamelin L, Allan D, Bredeson C. Improved prediction of CD34+ Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xiv cell yield before peripheral blood hematopoietic progenitor cell collection using a modified target value–tailored approach. Biol Blood Marrow Transplant. 2015. 101. Sholzberg M, Pavenski K, Shehata N, Cserti-Gazdewich C, Lin Y. Bleeding complications from the direct oral anticoagulants. BMC Hematol. 2015; 15: 1-5. 102. Simon AY, Sutherland MR, Pryzdial ELG. Dengue virus binding and replication by platelets. Blood. 2015; 126: 378-385. 103. Singh S, Dubinsky-Davidchik IS, Yang Y, Kluger R. Subunit-directed click coupling via doubly cross-linked hemoglobin efficiently produces readily purified functional bis-tetrameric oxygen carriers. Org Biomol Chem. 2015; 13: 11118-11128. 104. Siren EM, Singh S, Kluger R. Bioorthogonal phase-directed copper-catalyzed azide–alkyne cycloaddition (PCDuAAC) coupling of selectively cross-linked superoxide dismutase dimers produces a fully active bis-dimer. Org Biomol Chem. 2015; 13: 10244-10249. 105. Solh Z, Breakey V, Murthy P, Smith JW, Arnold DM. Triplets with neonatal alloimmune thrombocytopenia due to antibodies against human platelet antigen 1a. Transfusion. 2016. 106. Spitalnik SL, Triulzi D, Devine DV, Dzik WH, Eder AF, Gernsheimer T, Josephson CD, Kor DJ, Luban NLC, Roubinian NH, Mondoro T, Welniak LA, Zou S, Glynn S, for the State of the Science in Transfusion Medicine Working Group. 2015 proceedings of the National Heart, Lung, and Blood Institute's state of the science in transfusion medicine symposium. Transfusion. 2015; 55: 2282-2290. 107. Sutherland MR, Simon AY, Serrano K, Schubert P, Acker JP, Pryzdial ELG. Dengue virus persists and replicates during storage of platelet and red blood cell units. Transfusion. 2016. 108. Szkotak AJ, Lunty B, Nahirniak S, Clarke G. Interpretation of pretransfusion testing in obstetrical patients who have received antepartum Rh immunoglobulin prophylaxis. Vox Sang. 2016; 110: 5159. 109. Tabuchi A, Nickles HT, Kim M, Semple JW, Koch E, Brochard L, Slutsky AS, Pries AR, Kuebler WM. Acute lung injury causes asynchronous alveolar ventilation that can be corrected by individual sighs. Am J Respir Crit Care Med. 2015; 193: 396-406. 110. Tone K, Lalu M, Kilty SJ, Rosenberg E, Tinmouth A. Airway compromise and perioperative management of a patient with acquired factor XIII inhibitor. A&A Case Reports. 2015; 4: 120-124. 111. Tseng E, Crowther MA, Hillis CM. Bridging anticoagulation for interruption of warfarin in a patient with atrial fibrillation. CMAJ. 2016; 188: 361-362. 112. Vassallo R, Goldman M, Germain M, Lozano M, For the BEST Collaborative. Preoperative autologous blood donation: Waning indications in an era of improved blood safety. Transfus Med Rev. 2015; 29: 268-275. 113. Veljkovic V, Goeijenbier M, Glisic S, Veljkovic N, Perovic VR, Sencanski M, Branch DR, Paessler S. In silico analysis suggests repurposing of ibuprofen for prevention and treatment of Ebola virus disease. F1000Res. 2015; 4: 104. 114. Wang D, Shanina I, Toyofuku WM, Horwitz MS, Scott MD. Inhibition of autoimmune diabetes in NOD mice by miRNA therapy. PLoS One. 2015; 10: e0145179. 115. Wen J, Weinhart M, Lai B, Kizhakkedathu J, Brooks DE. Reversible hemostatic properties of sulfabetaine/quaternary ammonium modified hyperbranched polyglycerol. Biomaterials. 2016; 86: 42-55. 116. Ypma PF, van der Meer PF, Heddle NM, van Hilten JA, Stijnen T, Middelburg RA, Hervig T, van der Bom JG, Brand A, Kerkhoffs JL. A study protocol for a randomised controlled trial evaluating clinical effects of platelet transfusion products: The pathogen reduction evaluation and predictive analytical rating score (PREPAReS) trial. BMJ Open. 2016; 6: e010156. 117. Yu X, Menard M, Prechl J, Bhakta V, Sheffield WP, Lazarus AH. Monovalent Fc receptor blockade by an anti–Fcγ receptor/albumin fusion protein ameliorates murine ITP with abrogated toxicity. Blood. 2016; 127: 132-138. 118. Zeller M, Cristancho S, Mangel J, Goldszmidt M. Back to anatomy: Improving landmarking accuracy of clinical procedures using a novel approach to procedural teaching. South Med J. 2015; Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xv 108: 310-317. 119. Zeller MP, Goldszmidt M, Cristancho S, Johnson M, Creces D, Mangel J. Bare bones: A return to anatomy for teaching bone marrow biopsy and aspirate procedures. MedEdPORTAL Publications. 2015; 10091. 120. Zeller MP, Heddle NM, Kelton JG, Hamilton K, Wang G, Sholapur N, Carruthers J, Hsia C, Blais N, Toltl L, Hamm C, Pearson M-A, Arnold DM. Effect of a thrombopoietin receptor agonist on use of intravenous immune globulin in patients with immune thrombocytopenia. Transfusion. 2015. 121. Zeller MP, Sherbino J, Whitman L, Skeate R, Arnold DM. Design and implementation of a competency-based transfusion medicine training program in Canada. Transfus Med Rev. 2016; 30: 30-36. 122. Zwingerman R, Jain V, Hannon J, Zwingerman N, Clarke G. Alloimmune red blood cell antibodies: Prevalence and pathogenicity in a Canadian prenatal population. J Obstet Gynaecol Can. 2015; 37: 784-790. Review Articles 1. AABB Clinical Transfusion Medicine Committee, Heddle NM, Boeckh M, Grossman B, Jacobson J, Kleinman S, Tobian AAR, Webert K, Wong ECC, Roback JD. AABB committee report: Reducing transfusion-transmitted cytomegalovirus infections. Transfusion. 2016. 2. Arnold DM. Bleeding complications in immune thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2015; 2015: 237-242. 3. Chen D, Serrano K, Devine DV. Introducing the red cell storage lesion. ISBT Sci Ser. 2016; 11: 2633. 4. Damien P, Allan DS. Regenerative therapy and immune modulation using umbilical cord blood– derived cells. Biol Blood Marrow Transplant. 2015; 21: 1545-1554. 5. Eikelboom JW, Cook RJ, Barty R, Liu Y, Arnold DM, Crowther MA, Devereaux PJ, Ellis M, Figueroa P, Gallus A, Hirsh J, Kurz A, Roxby D, Sessler DI, Sharon Y, Sobieraj-Teague M, Warkentin TE, Webert KE, Heddle NM. Rationale and design of the informing fresh versus old red cell management (INFORM) trial: An international pragmatic randomized trial. Transfus Med Rev. 2016; 30: 25-29. 6. Flegel WA, De Castilho SL, Keller MA, Klapper EB, Moulds JM, Noizat-Pirenne F, Shehata N, Stack G, St-Louis M, Tormey CA, Waxman DA, Weinstock C, Wendel S, Denomme GA. Molecular immunohaematology round table discussions at the AABB annual meeting, Philadelphia 2014. Blood Transfus. 2015: 1-9. 7. Goldman M. Iron depletion and routine ferritin measurement in blood donors. ISBT Sci Ser. 2015; 10: 124-128. 8. Heddle N, Hillis C, Shih A. Best practices in the differential diagnosis and reporting of acute transfusion reactions. International Journal of Clinical Transfusion Medicine. 2016; 4: 1-14. 9. Hillis C, Crowther MA. Acute phase treatment of VTE: Anticoagulation, including non-vitamin K antagonist oral anticoagulants. Thromb Haemost. 2015; 113: 1193-1202. 10. Hou Y, Carrim N, Wang Y, Gallant RC, Marshall A, Ni H. Platelets in hemostasis and thrombosis: Novel mechanisms of fibrinogen-independent platelet aggregation and fibronectin-mediated protein wave of hemostasis. J Biomed Res. 2015; 29: 437-444. 11. Kapur R, Zufferey A, Boilard E, Semple JW. Nouvelle cuisine: Platelets served with inflammation. J Immunol. 2015; 194: 5579-5587. 12. Landry B, Valencia-Serna J, Gul-Uludag H, Jiang X, Janowska-Wieczorek A, Brandwein J, Uludag H. Progress in RNAi-mediated molecular therapy of acute and chronic myeloid leukemia. Mol Ther Nucleic Acids. 2015; 4: e240. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xvi 13. Marquez-Curtis LA, Janowska-Wieczorek A, McGann LE, Elliott JAW. Mesenchymal stromal cells derived from various tissues: Biological, clinical and cryopreservation aspects. Cryobiology. 2015; 71: 181-197. 14. Pineault N, Abu-Khader A. Advances in umbilical cord blood stem cell expansion and clinical translation. Exp Hematol. 2015; 43: 498-513. 15. Pineault N, Boisjoli GJ. Megakaryopoiesis and ex vivo differentiation of stem cells into megakaryocytes and platelets. ISBT Sci Ser. 2015; 10: 154-162. 16. Solh Z, Taccone MS, Marin S, Athale U, Breakey VR. Neurological PRESentations in sickle cell patients are not always stroke: A review of posterior reversible encephalopathy syndrome in sickle cell disease. Pediatr Blood Cancer. 2016. 17. Tsampalieros A, Knoll GA. Evaluation and management of proteinuria after kidney transplantation. Transplantation. 2015; 99: 2049-2060. 18. Walsh GM, Shih AW, Solh Z, Golder M, Schubert P, Fearon M, Sheffield WP. Blood-borne pathogens: A Canadian Blood Services centre for innovation symposium. Transfus Med Rev. 2016; 30: 53-68. 19. Wang Y, Gallant RC, Ni H. Extracellular matrix proteins in the regulation of thrombus formation. Curr Opin Hematol. 2016; 23: 280-287. 20. Yan M, Malinowski AK, Shehata N. Thrombocytopenic syndromes in pregnancy. Obstet Med. 2016; 9: 15-20. 21. Yu X, Lazarus AH. Targeting Fcγrs to treat antibody-dependent autoimmunity. Autoimmun Rev. 2016. 22. Zdravic D, Yougbare I, Vadasz B, Li C, Marshall AH, Chen P, Kjeldsen-Kragh J, Ni H. Fetal and neonatal alloimmune thrombocytopenia. Semin Fetal Neonatal Med. 2016; 21: 19-27. Comments/Letters/Editorials 1. Aslam R, Segel GB, Burack R, Spence SA, Speck ER, Guo L, Semple JW. Splenic lymphocyte subtypes in immune thrombocytopenia: Increased presence of a subtype of B-regulatory cells. Br J Haematol. 2016; 173: 159-160. 2. Chang TMS. Red blood cell replacement, or nanobiotherapeutics with enhanced red blood cell functions? Artif Cells Nanomed Biotechnol. 2015; 43: 145-147. 3. Hannon JL, Clarke G. Transfusion management of patients receiving daratumumab therapy for advanced plasma cell myeloma. Transfusion. 2015; 55: 2770-2770. 4. Hebert PC, Tinmouth A. Does age of blood matter? It depends. Am J Respir Crit Care Med. 2015; 192: 1150-1151. 5. Leach Bennett J. Making good policy decisions: A discipline we cannot afford to ignore. Transfusion. 2015; 55: 2775-2777. 6. Murti M, Louie K, Bigham M, Hoang LMN. Outbreak of shigellosis in a homeless shelter with healthcare worker transmission - British Columbia, April 2015. Infect Control Hosp Epidemiol. 2015; 36: 1372-1373. 7. Spinella PC, Acker J. Storage duration and other measures of quality of red blood cells for transfusion. JAMA. 2015; 314: 2509-2510. 8. Wang Y, Carrim N, Ni H. Fibronectin orchestrates thrombosis and hemostasis. Oncotarget. 2015; 6: 19350-19351. 9. Wang Y, Ni H. Fibronectin: Extra domain brings extra risk? Blood. 2015; 125: 3043-3044. 10. Webert KE. Splitting versus lumping: Reconsidering the definition of transfusion-related acute lung injury. Transfusion. 2015; 55: 927-929. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xvii 11. Yougbare I, Zdravic D, Ni H. Angiogenesis and bleeding disorders in FNAIT. Oncotarget. 2015; 6: 15724-15725. Book Sections 1. Roy R, Vidal S, Briard J, Shiao TC, Ben RN. Chapter 33: Synthesis of n-(4-methoxybenzyl)-2(α-dglucopyranosyl) acetamide. In Carbohydrate chemistry: Proven synthetic methods, volume 3. Published by CRC Press, 2015. Published Abstracts 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. Abu-Khader A, Bugnot G, Alsheikh M, Boisjoli G, Pasha R, Pineault N. The growth modulatory activities of osteoblast conditioned media on cord blood progenitors are mediated by soluble and cellular elements. Transfusion. 2015; 55: 12A. Abu-Khader A, Bugnot G, Alsheikh M, Pasha R, Pineault N. Conditioned medium represents a useful solution to increase the expansion of multipotent progenitors with strong platelet engraftment activity. Blood. 2015; 126: 4276. Abu-Khader A, Pasha R, Pineault N. Characterizing the impact of osteoblast conditioned media on the expansion and chemotaxis of hematopoietic stem and progenitor cell compartment. Canadian Society for Transfusion Medicine Website. 2015. Acker J. The complexity of tissue and organ cryopreservation: A call for interdisciplinary research. Cryobiology. 2015; 71: 170. Acker J. Innocuous intracellular ice formation: Ice growth in complex systems. Cryobiology. 2015; 71: 171. Acker J, Capicciotti C, Kurach J, Turner T, Mancini R, Ben R. Small molecule ice recrystallization inhibitors enable freezing of human red blood cells with reduced glycerol concentrations. Canadian Society for Transfusion Medicine Website. 2015. Acker J, Hansen A, Yi Q, Sondi N, Cserti-Gazdewich C, Pendergrast J, Hannach B. Introduction of a closed-system cell processor for red blood cell washing: Post-implementation monitoring of safety and efficacy. Canadian Society for Transfusion Medicine Website. 2015. Acker J, Howell A, Turner T, Yi Q. Evaluation of a point-of-care hemoglobinometer for measuring donor hemoglobin. Transfusion. 2015; 55: 98A. Acker JP, Alshalani A. Evaluation of stopped flow spectrophotometry to assess the effect of cell heterogeneity on cell permeability. Cryobiology. 2015; 71: 557-558. Acker JP, Capicciotti CJ, Kurach JD, Turner TR, Mancini RS, Ben RN. Small molecule ice recrystallization inhibitors enable freezing of human red blood cells with reduced glycerol concentrations. Transfus Med Rev. 2015; 29: 277. Ahlin J, Coroneos M, Cserti-Gazdewich C, Pavenski K, Lin Y, Barrett J, Malinowski A, Shehata N. The effect of red cell autoantibodies on pregnancy outcomes. Transfusion. 2015; 55: 173A. Al Habsi K, Liu Y, Heddle N, Carruthers J, Kelton J, McLeod A, MacEachern J, Mangel J, Anderson D, Vickars L, Tinmouth A, Arnold D. Prolonged responses to rituximab in patients with immune thrombocytopenia: Extended follow up of a randomized trial. Canadian Society for Transfusion Medicine Website. 2015. Al-Habsi KS, Shih AW, Barty R, Wang G, Elahie A, Azzam M, Siddiqui R, Parvizian M, Heddle NM, Athale UH, Goldman MR, Verhovsek MM. Red cell antigen genotyping compared to standard serological phenotyping in sickle cell disease patients in Canada: Potential for reducing alloimmunization. Blood. 2015; 126: 3404-3404. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xviii 14. Almizraq R, Yi Q, Acker J, On behalf of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Impact of technical and assay variation on reporting of hemolysis in stored red blood cell products. Transfusion. 2015; 55: 79A. 15. Amash A, Wang Y, Wang L, Lazarus AH. CD44 antibodies can directly inhibit murine macrophage Fc-gamma receptor and complement receptor 3-mediated phagocytosis. J Thromb Haemost. 2015; 13: 619. 16. Arbaeen A, Levin E, Serrano K, Devine D. Platelet concentrate functionality assessed by thromboelastography or rotational thromboelastometry: Platelet microvesicle contribution. Transfusion. 2015; 55: 75A. 17. Bakkour S, Acker J, Turner T, Chafets D, Lee T, Busch M. Processing method affects release of mitochondrial DNA damage-associated molecular patterns (DAMPs) in stored red blood cells. Transfusion. 2015; 55: 80A. 18. Barty R, Cook R, Liu Y, Acker J, Eikelboom J, Heddle N. Exploratory analysis of the association between donor sex and in-hospital mortality in transfusion recipients. Transfusion. 2015; 55: 23A. 19. Barty R, Liu Y, Pai M, Cook R, Arnold D, Heddle N. Group O red blood cells: Where is universal donor blood being used? Transfusion. 2015; 55: 153A. 20. Ben R, Briard JG, Poisson JS, Turner TR, Kurach JDR, Acker JP. Ice recrystallization inhibitors – mitigating cellular damage during freezing, transient warming and thawing. Cryobiology. 2015; 71: 171. 21. Bernardo L, Yu H, Lazarus A. Monoclonal antibodies can suppress the immune response to foreign erythrocytes independent of Fcγ receptor mediated red blood cell clearance and B-cell inhibition. Canadian Society for Transfusion Medicine Website. 2015. 22. Bhakta V, Sheffield W. Identification of alpha-1 proteinase inhibitor variants with enhanced specificity for activated factor XI over thrombin via combined phage display and bacterial lysate screening. J Thromb Haemost. 2015; 13: 258. 23. Bigham M, Skeate R, Hannach B, Young D, Swanson J, Fearon M. Canadian Blood Services’ response to four recent public health advisories of potential hepatitis A virus exposure. Canadian Society for Transfusion Medicine Website. 2015. 24. Bodnar M, Blain H, Onell R, Gerges H, Bolster L, Clarke G, Nahirniak S. Where is all the plasma going? A prospective audit of plasma usage. Canadian Society for Transfusion Medicine Website. 2015. 25. Bolte L, Oldfield L, Ison T, Lau W. An unexpected antibody: Apparent anti‐D in a D negative patient who had only received D negative blood. Canadian Society for Transfusion Medicine Website. 2015. 26. Briard J, Poisson J, Turner T, Chandran P, Acker J, Allan D, Ben R. Carbohydrate-based small molecule ice recrystallization inhibitors as cryopreservatives for red blood cells. Cryobiology. 2015; 71: 554. 27. Briard JG, Poisson JS, Turner TR, Kurach JD, Acker JP, Ben RN. Small molecule ice recrystallization inhibitors–a novel class of cryoprotectants. Cryobiology. 2015; 71: 540-541. 28. Bugnot G, Abu-Khader A, Pasha R, Pineault N. Characterization of the hematopoietic enhancing activity of medium conditioned with osteoblast. Cytotherapy. 2015; 17: S58. 29. Byrnes J, Duval C, Wang Y, Mooberry MJ, Lord S, Meijers J, Ni H, Ariens R, Wolberg A. Factor XIIIa crosslinking of fibrin a-chain mediates red blood cell retention in clots. J Thromb Haemost. 2015; 13: 55. 30. Carrim N, Zhu G, Reddy EC, Xu M, Xu X, Wang Y, Hou Y, L. M, Lavalle C, Li Y, Rui M, Petruzziello T, Lei X, Reheman A, Chen P, Wilkins JA, Hynes RO, Freedman J, Ni H. Integrin PSI Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xix 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. domain has endogenous thiol isomerase function and is a novel target for anti-thrombotic therapy. J Thromb Haemost. 2015; 13: 60-61. Carter RL, Talbot K, Smith T, Lee AY, Pryzdial EL. Oral factor Xa anticoagulants, rivaroxaban and apixaban, enhance clot dissolution in plasma. J Thromb Haemost. 2015; 13: 673. Celebi-Saltik B, Pineault N, Mantovani D. Expansion of hematopoietic progenitor cells in a new dynamic co-culture system. Tissue Eng Part A. 2015; 21: S182-183. Chai-Adisaksopha C, Calvin D, Hillis CM. Pulmonary complications in patients treated with tyrosine kinase inhibitors, a systematic review and meta-analysis. Blood. 2015; 126: 4030-4030. Chai-Adisaksopha C, Hillis CM, Lam W. Cardiovascular events in patients with chronic myelogenous leukemia treated with tyrosine kinase inhibitors: A systematic review and metaanalysis. J Clin Oncol. 2015; 33: 7056. Chargé S, Mastronardi C, Allan D, Elmoazzen H, Golder M. Facilitating cord blood research in Canada. Canadian Society for Transfusion Medicine Website. 2015. Chassé M, A T, English S, McIntyre L, Knoll G, Wolfe D, Wilson K, Shehata N, Forster A, van Walraven C, Fergusson DA. Effect of blood donor characteristics on transfusion outcomes: A systematic review and meta-analysis. Transfusion. 2015; 55: 123A. Chasse M, McIntyre L, Tinmouth A, English S, Acker J, Knoll G, Forster A, Shehata N, Wilson K, Ducharme R, van Walraven C, Fergusson D. Clinical effects of blood donor characteristics in transfusion recipients: A framework to study the blood donor-recipient continuum. Transfusion. 2015; 55: 42A. Chen D, Serrano K, Levin E, Devine D. Minimizing product wastage: Assessing the quality of a general red cell concentrate inventory compared to an RBC-sparing quality control testing strategy. Transfusion. 2015; 55: 234A. Chen Z, Schubert P, Culibrk B, Devine D. The effect of riboflavin/ultraviolet (UV) light treatment on mitochondrial function in platelet concentrates during storage. Transfusion. 2015; 55: 8A. Ciurcovich L, Stephens V, Petraszko T, Clarke G, Roland K. Investigation of anti-‐d in a patient following multiple Rh negative blood transfusions. Canadian Society for Transfusion Medicine Website. 2015. Clarke G, Hannon J, Lane D, Petraszko T, Alport E, Dolnik T, Eurich B, Grabner L. Prevalence of clinically significant red cell alloantibodies in a western Canadian prenatal population. Canadian Society for Transfusion Medicine Website. 2015. Cordi D, Dines I, Scalia V, Pilot G, Lalonde C, Fearon M. Donor re-entry at Canadian Blood Services. Canadian Society for Transfusion Medicine Website. 2015. Cote J, Morden J, Goldman M. Identification of RHCE variants in our patient & donor population. Canadian Society for Transfusion Medicine Website. 2015. Cserti-Gazdewich C, Lin Y, Lieberman L, Callum J, Pendergrast J, Pavenski K, Lau W, Skeate R, Latour C, Shehata N. Blood use and kell seroconversion-mitigation practices in females in five hospitals. Transfusion. 2015; 55: 172A. da Silveira Cavalcante L, Acker J, Holovati J. Effect of liposome treatment on rat red blood cell membrane microvesiculation during hypothermic storage. Canadian Society for Transfusion Medicine Website. 2015. da Silveira Cavalcante L, Feng Q, Chin-Yee I, Acker JP, Holovati JL. Safety of transfusing liposome-treated rat RBCs in an anemic rat model. Cryobiology. 2015; 71: 553. de Korte D, Fitzpatrick A, Morrison A, Thibault L, Marks D, Seldsam A, Acker J. In vitro evaluation of the effects of timing of irradiation on stored red cell concentrates. Vox Sang. 2015; 109: 154. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xx 48. de Korte D, Thibault L, Morrison A, Fitzpatrick A, Marks D, Seltsam A, Acker J, On behalf of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Timing of gamma irradiation and sex of blood donor influences in vitro characteristics of red cell concentrates. Transfusion. 2015; 55: 38A. 49. Delaney M, Taune-Wikman A, van de Watering L, Verdoes J, Emery S, Murphy M, Flach S, Staves J, Arnold D, Kaufman R, Ziman A, Harm S, Fung M, Dunbar N, Buser A, Meyer E, Savoia H, Abeysinghe P, Heddle N, Tinmouth A, Traore A, Yazer H, On behalf of the BEST Collaborative. Red blood cell transfusion antigen matching influence on gestational outcomes (AMIGO) study. Transfusion. 2015; 55: 25A. 50. Devine D. Introducing the red cell storage lesion. Vox Sang. 2015; 109: 3. 51. Doncaster C, Webert K. Contingency planning requires hospital participation. Canadian Society for Transfusion Medicine Website. 2015. 52. Duncan J, Nahirniak S, Onell R, Clarke G. Two cases of the variant dau5 RHD allele associated with anti d mediated hemolytic disease of the newborn. Canadian Society for Transfusion Medicine Website. 2015. 53. Elmoazzen H, Halpenny M, Martin L, Mostert K, Allan D, Petraszko T, Dibdin N, Campbell T, Letcher B, Yang L. Numeration of colony‐forming unit granulocyte‐macrophage (CFU-GM) colonies in cord blood using an automated instrument: STEMvisionTM. Canadian Society for Transfusion Medicine Website. 2015. 54. Elmoazzen H, Halpenny M, Martin L, Mostert K, Allan D, Petraszko T, Dibdin N, Campbell T, Letcher B, Yang L. Umbilical cord blood processing: First year operations at the Canadian Blood Services, National Public Cord Blood Bank. Canadian Society for Transfusion Medicine Website. 2015. 55. Elmoazzen H, Halpenny M, Martin L, Mostert K, Lawless T, Quinlan E, Allan D, Petraszko T, Dibdin N, Campbell T, Yang L. Umbilical cord blood collection: First year operations at the Canadian Blood Services, National Public Cord Blood Bank. Canadian Society for Transfusion Medicine Website. 2015. 56. Estey M, Nahirniak S, Bruce A, Clarke G. Acquired hemoglobinopathy following exchange transfusion for sickle cell anemia. Canadian Society for Transfusion Medicine Website. 2015. 57. Fearon M, O’Brien S, Delage G, Scalia V, Bernier F, Dubuc S, Germain M, Pilot G, Yi Q, Lindsay R. Human babesiosis and tick distribution in Canada. Canadian Society for Transfusion Medicine Website. 2015. 58. Fearon M, Skeate R, Bigham M, Cronin P, Biemans J, Guenette K, McIntyre L, Shimla S, Dunbar M. Ebola preparedness at Canadian Blood Services. Canadian Society for Transfusion Medicine Website. 2015. 59. Fish EN, McCarthy SD, Hoenen T, Branch DR. IFN-β treatment for Ebola virus disease: Bench to bedside. Cytokine. 2015; 76: 77. 60. Goldman M, Coté J, Hannon J, Clarke G, Ochoa-Garay G, Pambrun C. RHD genotyping for prenatal patients with a serologic weak D phenotype. Canadian Society for Transfusion Medicine Website. 2015. 61. Goldman M, Coté J, Hannon J, Clarke G, Ochoa-Garay G, Pambrun C. RHD genotyping for prenatal patients with a serologic weak D phenotype. Transfus Med Rev. 2015; 29: 276-277. 62. Goldman M, Land K, Robillard P, Tomasulo P, Wiersum-Osselton J. Development of standard definitions for surveillance of complications related to blood donation. Vox Sang. 2015; 109: 36. 63. Goldman M, Uzicanin S, O’Brien S, Scalia J, Scalia V. Iron deficient blood donors - degree of understanding and actions taken after notification. Vox Sang. 2015; 109: 146. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxi 64. Goldman M, Uzicanin S, Scalia V, O’Brien S. Ferritin testing in Canadian blood donors. Transfusion. 2015; 55: 22A. 65. Guo L, Speck E, Aslam R, Kapur R, Ni H, Semple J. Suppression of cell-mediated immune thrombocytopenia (ITP) by B cell depletion therapy in a murine model. J Thromb Haemost. 2015; 13: 146-147. 66. Halpenny M, Elmoazzen H, Martin L, Mostert K, Allan D, Petraszko T, Dibdin N, Campbell T, Letcher B, Murphy K, den Admirant M, Acker J, Yang L. Numeration of colony-forming unitgranulocyte-macrophage (CFU-GM) colonies in cord blood by using an automated instrument: STEMvision. Transfusion. 2015; 55: 52A. 67. Halpenny M, Elmoazzen H, Martin L, Mostert K, Allan D, Petraszko T, Dibdin N, Campbell T, Letcher B, Yang L. Cord blood processing: First-year operations at the Canadian Blood Services’ National Public Cord Blood Bank. Transfusion. 2015; 55: 49A. 68. Hammond D, Saidenberg E, Tinmouth A. Single-center experience with rituximab in the treatment of inhibitor-associated hemostatic disorders. J Thromb Haemost. 2015; 13: 762. 69. Hannon J, Clarke G, Berardi P, Barr G, Cote J, Fallis R, Alport T, Lane D, Petraszko T, Ochoa G, Goldman M. Resolving variable maternal D typing by using serology and genotyping in selected prenatal patients. Transfusion. 2015; 55: 149A. 70. Hannon J, Senft N, Clarke G. Resolution of "possible D" phenotype reported following genotyping using Immucor BioArray RHD BeadChip™ kit. Canadian Society for Transfusion Medicine Website. 2015. 71. Heddle N, Liu Y, Acker J, Barty R, Eikelboom J, Arnold D, Hsia C, O’Brien S, Webert K, Cook RJ. Exploratory analysis of a blood processing method and in-hospital mortality. Transfusion. 2015; 55: 23A. 72. Howell A, Turner T, Hansen A, Acker J. Pre-processing length of storage and method of glycerolization affect the outdate of RCCs cryopreserved by using a closed-system cell processor. Transfusion. 2015; 55: 78A. 73. Hume A, Ddungu H, Kajumbula H, Kyeyune-Byabazaire D, Jackson O, Ramirez-Arcos S, Tobian A. Patient characteristics and rate of acute transfusion reactions to platelet transfusions in Uganda. Vox Sang. 2015; 109: 364. 74. Hume A, Ddungu H, Kajumbula H, Kyeyune-Byabazaire D, Jackson O, Ramirez-Arcos S, Tobian A. Rate of platelet bacterial contamination in Uganda. Vox Sang. 2015; 109: 171. 75. Jordan A, Yi Q, Acker J. Age matters: How donor characteristics influence red cell product quality. Transfusion. 2015; 55: 77A. 76. Kapur R, Kim M, Shanmugabhavananthan S, Speck ER, Aslam R, Guo L, Zufferey A, Semple JW. C-reactive protein (CRP) enhances murine antibody-mediated transfusion related acute lung injury (TRALI). Blood. 2015; 126: 3561. 77. Kapur R, Kim M, Shanmugabhavananthan S, Speck ER, Aslam R, Zufferey A, Semple JW. CD4+ CD25+ Foxp3+ T regulatory cells protect against murine antibody-mediated transfusion-related acute lung injury (TRALI). Blood. 2015; 126: 2342. 78. Klein-Bosgoed C, Schubert P, Devine D. Pathogen inactivation treatment affects platelet messenger RNA transcripts differently. Transfusion. 2015; 55: 39A. 79. Kozlowski H, Lai E, McCarthy S, Branch D. Extracellular histones: Identifying a new host factor to regulate HIV-1 infection. Canadian Association for HIV/AIDS Research Website. 2015. 80. Lau W, Bolte L, Oldfield L. ABO discrepancy in a paediatric patient. Canadian Society for Transfusion Medicine Website. 2015. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxii 81. Lauzon D, Owens W, Tremblay D, Coovadia A. On the brink - testing Ontario’s plan for blood shortages Canadian Society for Transfusion Medicine Website. 2015. 82. Lusianti RE, Lahmann JM, Dickinson A, Benson JD, Acker JP, Higgins AZ. Accelerating post-thaw erythrocyte washing using microfluidics. Cryobiology. 2015; 71: 538-539. 83. Manning N, Heddle N, Arnold D, Crowther M, Siegal D. Interventions to reduce blood loss from laboratory testing in critically ill patients and impact on transfusion: A systematic review. Canadian Society for Transfusion Medicine Website. 2015. 84. Manning N, Heddle NM, Arnold D, Crowther MA, Siegal D. Interventions to reduce blood loss from laboratory testing in critically ill patients and impact on transfusion: A systematic review. J Thromb Haemost. 2015; 13: 974. 85. McCarthy S, Kozlowski H, Branch D. HIV-1 nucleoside analogues inhibit ebola virus replication: New application of cART. Canadian Association for HIV/AIDS Research Website. 2015. 86. McVey M, Spring CM, Kuebler WM. Optimizing procedures for transport and processing of clinical cerebrospinal fluids to preserve extracellular vesicular (EVs) miRNAs. J Extracell Vesicles. 2015; 4: 163. 87. Menard M, Jen C, Lazarus A. Anti-erythrocyte antibody mediated phagocytosis in vitro is linked to its therapeutic role in murine immune thrombocytopenia (ITP). Canadian Society for Transfusion Medicine Website. 2015. 88. Mithoowani S, Gregory-Miller K, Goy J, Miller MC, Moroozi N, Arnold DM. Higher or lower dose corticosteroids for primary immune thrombocytopenia: Systematic review and meta-analysis. J Thromb Haemost. 2015; 13: 40. 89. Mundil D, Cameron-Vendrig A, Shikatani EA, Reheman A, Siraj MA, Momen A, Afroze T, Backx P, Ni H, Husain M. Targeting molecular pathways in diabetes associated cardiovascular disease. Cardiology. 2015; 131(suppl 2): 171. 90. Nahirniak S, Lunty B, Winchester D, Malone P, Hamacher K, Gaal H, Miller S, Onell R, Clarke G. Changing antibody investigation process to save time, money, and, hopefully, patients. Transfusion. 2015; 55: 137A. 91. Nahirniak S, Schmitt K, Prokopchuk-Gauk O, Blain H, Onell R, Clarke G. Where do all the red cells go – 2004 versus 2014? Transfusion. 2015; 55: 33A. 92. Nahirniak S, Yue T, Engels P, Widder S, Clarke G. Intraosseous specimens: Suitable for pretransfusion testing in trauma? Transfusion. 2015; 55: 168A. 93. O’Brien S, Delage G, Seed C, Pillonel J, Fabra C, Davison K, Kitchen A, Steele W, Leiby D. Comparison of policies to address imported malaria in five non-endemic countries. Vox Sang. 2015; 109: 238. 94. O’Brien S, Goldman M, Vassallo R, Steele W, Di Angelantonio E, Van den Hurk K, Custer B, Dubuc S, Germain M. Comparison of donor and general population demographics in Canada, the Netherlands, England and the United States: A BEST collaborative group study Vox Sang. 2015; 109. 95. O’Brien S, Osmond L, Goldman M. Impact of a 5-year deferral for men who have sex with men on donor compliance. Transfusion. 2015; 55: 21A. 96. O’Brien S, Osmond L, Goldman M. Transmissible disease risk factors among men who have sex with men - comparison of blood donors vs. community men. Vox Sang. 2015; 109: 202. 97. O'Brien S, Fearon M, Nahirniak S, Scalia V, Preiksaitis J. Prevalence and incidence of cytomegalovirus in blood donors and transplant patients. Canadian Society for Transfusion Medicine Website. 2015. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxiii 98. O'Brien S, Osmond L, Goldman M, Fearon M. Donor travel survey. Canadian Society for Transfusion Medicine Website. 2015. 99. O'Brien S, Uzicanin S, Scalia V, Goldman M. Iron deficiency in apheresis donors. Canadian Society for Transfusion Medicine Website. 2015. 100. Pigeau S, Cote J, Gill B, Goldman M. The identification of U- and U+ var donor RBC units. Canadian Society for Transfusion Medicine Website. 2015. 101. Pineault N, Bugnot G, Pasha R, Abu-Khader A. Characterization of the hematopoietic enhancing activity of medium conditioned with osteoblasts. Canadian Society for Transfusion Medicine Website. 2015. 102. Porter S, Lew K, Clarke G, Nahirniak S. Red blood cell usage and iron overload trends in chronically transfused patients. Canadian Society for Transfusion Medicine Website. 2015. 103. Poseluzny D, Lagerquist O, Werstiuk G, Ourdev I, Slomp J, Nahirniak S, Clarke G. What is the true cost of a unit of red blood cells in Canada? A costing model for hospital use. Canadian Society for Transfusion Medicine Website. 2015. 104. Prokopchuk-Gauk O, Schmitt K, Blain H, Clarke G, Nahirniak S. Hemoglobin level as a trigger for red cell transfusion: An analysis of local practice. Transfusion. 2015; 55: 177A. 105. Pryzdial E. Hemostasis-pathogen interplay: The virus envelope. J Thromb Haemost. 2015; 13: 40. 106. Pryzdial E, Sutherland M, Simon A. Production of infectious dengue virus by platelets. Canadian Society for Transfusion Medicine Website. 2015. 107. Pryzdial EL, Sutherland MR, Simon AY. Production of infectious dengue virus by platelets. Transfus Med Rev. 2015; 29: 276. 108. Ramirez-Arcos S, Kou Y, Pagotto F, Hannach B. Fatal false‐negative transfusion infection with a buffy coat platelet pool contaminated with staphylococcus epidermidis: A case report. Canadian Society for Transfusion Medicine Website. 2015. 109. Ramirez-Arcos S, Kou Y, Pagotto F, Hannach B. Fatal transfusion-transmitted staphylococcus epidermidis: A case report. Vox Sang. 2015; 109: 62. 110. Ramirez-Arcos S, Kou Y, Perkins H, Halpenny M, Elmoazzen H, Toye B. Validation of microbial testing in hematopoietic progenitor cell – apheresis product at Canadian Blood Services. Canadian Society for Transfusion Medicine Website. 2015. 111. Ramirez-Arcos S, Kou Y, Taha M, Goldman M. Evaluation of alternative skin disinfection methods for donors allergic to chlorhexidine. Canadian Society for Transfusion Medicine Website. 2015. 112. Ramirez-Arcos S, Kou Y, Taha M, Goldman M. Selecting an alternative skin disinfection method for donors allergic to chlorhexidine at Canadian Blood Services. Vox Sang. 2015; 109: 74. 113. Ramirez-Arcos S, McDonald C, Benjamin R. Survey for bacterial testing in platelet concentrates in Latin America. Vox Sang. 2015; 109: 236. 114. Ramirez-Arcos S, Taha M, Schubert P, Maurer E, Jenkins C, NetCAD. Insights into bacterial survival and distribution during buffy coat platelet production. Vox Sang. 2015; 109: 231. 115. Rebulla P, Vaglio S, Aprili G, Beccaria F, Coluzzi S, Girelli G, Graf M, Isernia P, Marconi M, Olivero B, Rinaldi M, Salvaneschi L, Scarpato N, Strada P, McCullough J, Heddle N, Grazzini G. Clinical efficacy and safety of platelets in additive solution treated with two commercial pathogen reduction technologies. Transfusion. 2015; 55: 3A. 116. Rentas S, Holzapfel N, Belew M, Voisin V, Pratt G, Bader G, Yeo G, Hope K. Musashi-2 postranscriptionally attenuates aryl hydrocarbon receptor signaling to expand human hematopoietic stem cells. Exp Hematol. 2015; 43: S90. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxiv 117. Schubert P, Culibrk B, Devine D. p38MAP kinase regulates protein synthesis in platelets via eIF4E phosphorylation. Transfusion. 2015; 55: 118A. 118. Schubert P, Culibrk B, Fang T, Karwal S, Devine D. Inhibition of Wnt signaling in platelets reduces storage lesion. Transfusion. 2015; 55: 80A. 119. Schubert P, Culibrk B, Karwal S, Goodrich R, Devine D. Protein synthesis in platelets despite pathogen inactivation with riboflavin and UV light. Transfusion. 2015; 55: 80A. 120. Schubert P, Kelly A, Lau T, Smethurst P, Jansen S, Cardigan R, Devine D. Proteomic analysis of platelets from donors of different levels of responsiveness. Vox Sang. 2015; 109: 166. 121. Schulman S, Carrier M, Lee AY, Shivakumar S, Blostein M, Spencer FA, Solymoss S, Barty R, Wang G, Heddle N, Douketis JD. Perioperative management of dabigatran: A prospective cohort study. J Thromb Haemost. 2015; 13: 203. 122. Semple J, Tabuchi A, Kim M, McKenzie C, Kleuser B, Rotstein O, Arenz C, Kuebler W, McVey M. Aged allogeneic platelets trigger antibody-independent transfusion related acute lung injury via a sphingolipid-dependent mechanism. Am J Respir Crit Care Med. 2015; 191: A2382. 123. Semple JW, Speck ER, Aslam R, Kim M, Zufferey A, Ni H, Catalina M, Francovitch R. Successful treatment of thrombocytopenia with staphylococcal protein a (PRTX-100) in a murine model of immune thrombocytopenia (ITP). Blood. 2015; 126: 1045. 124. Serrano K, Pambrun C, Levin E, Devine D. Supernatant reduction of gamma-irradiated red cell concentrates minimizes potentially harmful substances present in transfusion aliquots for neonates. Transfusion. 2015; 55: 77A. 125. Sheffield W, Eltringham-Smith L, Ni H, Pryzdial E. Identical bleeding reduction in coagulopathic mice transfused with four coagulation factors or plasma. Canadian Society for Transfusion Medicine Website. 2015. 126. Shehata N, Chasse M, Colas J, Ducharme R, Malinowsk A, Forster A, Fergusson D, Tinmouth A, Lawrence N, Wilson K. Risk factors for red cell transfusion in obstetric patients. Transfusion. 2015; 55: 174A. 127. Sheppard D, Tay J, Palmer D, Xenocostas A, Doulaverakis C, Huebsch L, McDiarmid S, Mallick R, Martin L, Birch P, Hamelin L, Allan D, Bredeson C. Improved prediction of CD34+ cell yield prior to peripheral blood hematopoietic progenitor cell collection using a modified target value-tailored approach. Canadian Society for Transfusion Medicine Website. 2015. 128. Shih A, Bhagirath V, Liaw P, Acker J, Eikelboom J, Heddle N. Quantification of cell free DNA in red blood cell concentrates produced via whole blood or buffy coat methods. Canadian Society for Transfusion Medicine Website. 2015. 129. Shih A, Bhagirath V, Liaw P, Acker J, Eikelboom J, Heddle N. Quantification of cell-free DNA in red blood cell concentrates produced via buffy coat or whole blood-filtered methods. Transfusion. 2015; 55: 9A. 130. Shih A, Bhagirath VC, Liaw PC, Acker J, Eikelboom J, Heddle N. Quantification of cell free DNA in red blood cell concentrates produced via buffy coat (B1) or whole blood (B2) methods. J Thromb Haemost. 2015; 13: 468. 131. Sholapur NS, Hillis CM, Crowther MA, Leber B, Khokhar F, Cook R, Barr R, Heddle NM. Assessing disease stability of patients with myelodysplastic syndrome for an age of blood randomized controlled trial: A chart review. Blood. 2015; 126: 5252-5252. 132. Sholapur NS, Lane S, Hillis CM, Crowther MA, Leber B, Cook R, Barr R, Heddle NM. A qualitative research study to understand post-transfusion well-being in patients with myelodysplastic syndromes. Blood. 2015; 126: 4446-4446. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxv 133. Singh S, Kluger R. Bioorthogonal CuAAC-based hemoglobin-hemoglobin coupling optimized by regioselective serial cross-linking. Pacifichem 2015. 2015: 221. 134. Sowemimo-Coker S, Acker J, Narla M, Popovsky M, Turner T, Hansen A, Romero V, Ceniza M, Herschel L, Herzog E, Dumont L. Development of a statistical model for predicting in vivo viability of red blood cells: Importance of red cell membrane changes. Transfusion. 2015; 55: 56A. 135. Spindler-Raffel E, McDonald C, Benjamin R, Aplin K, Gabriel C, Hourfar K, Jacobs M, Keil S, de Korte D, Mukhtar Z, Niekerk T, Ramirez-Arcos S, Rojo J, Satake M, Seltsam A, Stoermer M, Wagner S. Platelet transfusion relevant bacteria reference strains - suitability test of different candidate strains. Vox Sang. 2015; 109: 230. 136. Spindler-Raffel E, McDonald C, Benjamin R, Aplin K, Gabriel C, Jacobs M, Ramirez-Arcos S, Satake M, Seltsam A, Wagner S. Platelet transfusion transmitted relevant bacteria - growth ability of different Morganella morganii strains in platelets. Vox Sang. 2015; 109: 235. 137. Sutherland MR, Simon AY, Pryzdial ELG. The direct dengue virus-platelet interaction: Generation of infectious progeny. J Thromb Haemost. 2015; 13: 199. 138. Szkotak A, Clarke G, Vandergouwe L, Stang L. Province wide implementation of the thrombin time for qualitative assessment of dabigatran clearance. J Thromb Haemost. 2015; 13: 539. 139. Thompson T, Tinmouth A, Pinkerton P, Callum J, Hsia C, Shepherd L, Webert K. A repeat provincial audit of frozen plasma (FP) and prothrombin complex concentrates (PCCs). Transfusion. 2015; 55: 162A. 140. Traore A, Chan A, Iorio A, Heddle N, Walker I, on behalf of Association of Hemophilia Clinic Directors of Canada. Utilization of anti-inhibitors products and inhibitors status of severe hemophilia patients: 5 years national data from the Canadian hemophilia assessment and resource management system. J Thromb Haemost. 2015; 13: 362. 141. Turley E, Delisle M, Lalji S, Skoll A, Nelson T, Goldman M, Clarke G, Au N. Del phenotype with anti-D formation and severe HDFN due to a novel RHD mutation: A case report. Canadian Society for Transfusion Medicine Website. 2015. 142. Vadasz B, Zdravic D, Chen P, Yougbare I, Zhu G, Frampton J, Poncz M, Freedman J, Ni H. Pathogenesis of anti-integrin αIIb-mediated fetal and neonatal alloimmune thrombocytopenia: Establishment of novel murine models in αIIb deficient and human αIIb transgenic mice. J Thromb Haemost. 2015; 13: 871. 143. Walsh G, Chargé S. ResearchUnits: Development and evaluation of a knowledge mobilization tool for transfusion medicine research. Canadian Society for Transfusion Medicine Website. 2015. 144. Ward S, Kelly A. Risk-based decision-making for blood safety. Vox Sang. 2015; 109: 82. 145. Xu M, Carrim N, Zhu G, Chen P, Ni H. Anti-GPIbalpha antibodies induce immune thrombocytopenia in distinct pathways: Fc-dependent vs. Fc-independent. J Thromb Haemost. 2015; 13: 870-871. 146. Xu M, Ma L, Carrim N, Yougbare I, Li J, Chen P, Zhu G, Ni H. Platelet GPIba is important for thrombopoietin production and thrombopoietin-induced platelet generation. Blood. 2015; 126: 12. 147. Yanitski K, Gaal H, Clarke G, Nahirniak S. Rh (D) alloimmunization in Rh negative patients receiving Rh positive red cells. Canadian Society for Transfusion Medicine Website. 2015. 148. Yau J, Hou Y, Lei X, Teoh H, Quan A, Singh K, Ramadan A, Ni H, Verma S. Endothelial autophagy regulates arterial thrombus formation in mice. Can J Cardiol. 2015; 31: S196-S197. 149. Yau JW, Hou Y, Lei X, Ramadan A, Teoh H, Quan A, Singh KK, Al-Omran M, Ni H, Verma S. A novel role of endothelial autophagy in the regulation of thrombosis in vivo. Circulation. 2015; 132: A10824. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxvi 150. Yougbare I, Tai WS, Zdravic D, Vadasz B, Marshall AH, Chen P, Zhu G, Leong-Poi H, Adamson SL, Freedman J, Ni H. Pathology of placenta in fetal and neonatal immune thrombocytopenia: Roles of TH17 immune responses, uterine natural killers cells and angiogenic factors. Am J Reprod Immunol. 2015; 73: 60. 151. Yougbare I, Tai W-S, Zdravic D, Vadasz B, Marshall AH, Chen P, Zhu G, Leong-Poi H, Qu D, Yu LX, Adamson LS, Sled J, Freedman J, Ni H. Pathology of placenta in fetal and neonatal immune thrombocytopenia: Roles of TH17 immune responses, anti-platelet antibodies and angiogenic factors. J Thromb Haemost. 2015; 13: 105. 152. Yougbare I, Wei-she T, Zdravic D, Chen P, Zhu G, Leong-Poi H, Dawei Q, Yu XL, Lee SA, Sled J, Freedman J, Ni H. Natural killer cells contribute to pathophysiology of placenta leading to miscarriage in fetal and neonatal alloimmune thrombocytopenia. Blood. 2015; 126: 2254-2254. 153. Zeller M, Arnold D, Al Habsi K, Cserti‐Gazdewich C, Delage G, Lebrun A, Heddle N. An overview of Donath Landsteiner testing in Canada: Implications for testing. Canadian Society for Transfusion Medicine Website. 2015. 154. Zeller M, Heddle N, Kelton J, Hamilton K, Wang G, Sholapur N, Carruthers J, Hsia C, Pearson M, Arnold D. Patterns of practice and cost of therapy of immune thrombocytopenia since the introduction of thrombopoietin receptor agonists. Canadian Society for Transfusion Medicine Website. 2015. 155. Zeller M, van de Watering L, Heddle N, Yazer M, On behalf of the BEST Collaborative. Group O and RhD negative utilization patterns and associated hospital policies: A multicenter, international study. Transfusion. 2015; 55: 154A. 156. Zufferey A, Speck ER, Guo L, Aslam R, Kapur R, Semple JW. MHC class I antigen presentation by megakaryocytes. J Thromb Haemost. 2015; 13: 617. 157. Zufferey A, Speck ER, Guo L, Aslam R, Kapur R, Semple JW. Murine bone marrow-derived megakaryocytes are capable of antigen cross-presentation on major histocompatibility class (MHC) I molecules. Blood. 2015; 126: 3465. Canadian Blood Services Circular of Information 1. Jenkins C. Circular of information for the use of human blood components: Hematopoietic progenitor cells (HPC), cord blood. Blood.ca website. 2015. 2. Jenkins C. Circular of information for the use of human blood components: Plasma components. Blood.ca website. 2015. 3. Jenkins C. Circular of information for the use of human blood components: Platelets. Blood.ca website. 2015. 4. Jenkins C. Circular of information for the use of human blood components: Red blood cells, leukocytes reduced (LR). Blood.ca website. 2015. Canadian Blood Services Website Publications 1. Acker JP. ResearchUnit: Bath time for blood cells: Improving the red blood cell washing process. Transfusionmedicine.ca website. 2015. 2. Goldman M. ResearchUnit: ABO...K? Investigating if young females need more than ABOcompatible blood. Transfusionmedicine.ca website. 2015. 3. Goldman M, Hannaford K, Hannon J, Berardi P. Molecular immunohematology at Canadian Blood Services: Red cell antigen genotyping. Transfusionmedicine.ca website. 2016. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxvii 4. Goldman M, Scalia V, Devine D. Donor selection, transmissible disease testing and pathogen reduction. In Clinical Guide to Transfusion. Edited by Clarke G, Chargé S. Published in transfusionmedicine.ca by Canadian Blood Services, 2015. 5. Heddle NM, Acker JP. ResearchUnit: Datamining: Digging for deeper understanding of blood components and transfusion outcomes. Transfusionmedicine.ca website. 2016. 6. Lazarus A. ResearchUnit: Single site solution: Engineering novel antibodies for the treatment of ITP. Transfusionmedicine.ca website. 2015. 7. Nahirniak S. Albumin. In Clinical Guide to Transfusion. Edited by Clarke G, Chargé S. Published in transfusionmedicine.ca by Canadian Blood Services, 2015. 8. Ni H. ResearchUnit: Novel discovery reveals new diagnostic markers and treatment targets for bleeding disorder. Transfusionmedicine.ca website. 2015. 9. Poon MC, Goodyear MD, Lee A. Coagulation factor concentrates. In Clinical Guide to Transfusion. Edited by Clarke G, Chargé S. Published in transfusionmedicine.ca by Canadian Blood Services, 2015. 10. Poon MC, Goodyear MD, Lee A. Hemostatic disorders. In Clinical Guide to Transfusion. Edited by Clarke G, Chargé S. Published in transfusionmedicine.ca by Canadian Blood Services, 2015. 11. Pryzdial EL. ResearchUnit: Hijacked: The role of platelets in dengue virus infection revealed. Transfusionmedicine.ca website. 2016. 12. Serrano K. ResearchUnit: Making the cut: Protein breakdown in platelets during storage. Transfusionmedicine.ca website. 2015. 13. Withers SG, Kizhakkedathu J. ResearchUnit: Breakthrough brings universal blood a step closer to reality. Transfusionmedicine.ca website. 2015. Fast Policy Facts 1. Toews M, Caulfield T, Nelson E, Ogbogu U, Hartell D. Rights and interests in human bodies and biological materials. Canadian National Transplant Research Program Fast Policy Facts: Human Bodies and Biological Materials. 2015. Technical Reports 1. Acker JP, Yi QL. CompoLab evaluation - summary of statistical analysis. Internal report submitted to Canadian Blood Services. 2015. 2. Blake J. Methods for estimating donor deferrals with the CompoLab hemoglobin measurement system. Internal report submitted to Canadian Blood Services. 2015. 3. Chargé SB. Opportunities for Canadian Blood Services in delivering cellular therapies. Part one: Understanding the field of cellular therapy. Internal report submitted to Canadian Blood Services, Executive Management Team. 2015. 4. Hillis C, Shih A, Jamula E, Shah N, Lin Y, Heddle NM. Final report to MOHLTC - audit of intravenous immune globulin (IVIG) indications and effectiveness in Ontario tertiary care centres. External report submitted to Ontario Regional Blood Coordination Network. 2015. 5. Howell A, Acker J. Hematocrit adjustment pilot: Glycerolization and deglycerolization of red blood cell products using the ACP-215. Internal report submitted to Canadian Blood Services. 2015. 6. Howell A, Acker J. Volume reduction pilot: Glycerolization and deglycerolization of red blood cell products using the ACP-215. Internal report submitted to Canadian Blood Services. 2015. 7. Howell A, Acker JP. Phase 1: Glycerolization and deglycerolization of red blood cell products using the ACP-215. Internal report submitted to Canadian Blood Services. 2015. 8. Howell A, Acker JP, Jenkins C. Protocol for preparing a whole blood sample with a hemoglobin concentration of 120-130 g/L. Internal report submitted to Canadian Blood Services. 2015. 9. Howell A, Turner TR, Acker JP. Unit investigation: Possible high K+ in irradiated RCC unit. Internal report submitted to Canadian Blood Services. 2015. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxviii 10. Lazarus A, Ni H. Environmental scan: Are platelet additive solutions ready for prime time in Canada? Internal report submitted to Canadian Blood Services, Product Innovation Operating Committee. 2015. 11. Mastronardi C, Jenkins C. Elimination of CompoCool elements development study. Internal report submitted to Canadian Blood Services, Supply Chain - Production Process Management. 2015. 12. Mastronardi C, Jenkins C. Rinse modification - platelet pooling process development study. Internal report submitted to Canadian Blood Services, Supply Chain - Production Process Management. 2015. 13. Ramirez-Arcos S. Antibiotic neutralization in cord blood by-products plasma and RBCs used for sterility testing. Internal report submitted to Canadian Blood Services, Cord Blood Bank & Stem Cell Manufacturing. 2016. 14. Ramirez-Arcos S. Bacterial detection testing - proficiency test kits and proficiency testing results reports. Internal report submitted to Canadian Blood Services, Wanda Lefresne, Associate Director, Production Process Management. 2015. 15. Ramirez-Arcos S. Bacterial growth during storage of thawed cryoprecipitate at 20-24C for 24 hours. Internal report submitted to Canadian Blood Services. 2016. 16. Ramirez-Arcos S. Bacterial growth in culture bottles used for sterility testing of cord blood units. Internal report submitted to Canadian Blood Services, Manager, Stem Cell Manufacturing and Hospital Services. 2015. 17. Ramirez-Arcos S. Certificate of conformance - BPA and BPN lots. Internal report submitted to Canadian Blood Services, Quality Assurance. 2015-2016. 18. Ramirez-Arcos S. Ten years of platelet screening for bacterial contamination at Canadian Blood Services. Internal report submitted to Canadian Blood Services. 2015. 19. Sheffield W, Pryzdial E. Environmental scan: Freeze-dried (lyophilized) plasma. Internal report submitted to Canadian Blood Services, Product Innovation Operating Committee. 2015. 20. Sheffield WP, Bhakta V, Ramirez-Arcos S, Kou Y. Investigation of FP unit returned by hospital customer on 2015-11-12. Internal report submitted to Canadian Blood Services, Craig Jenkins, Senior Manager, Quality Monitoring Program. 2015. 21. Turner T, Acker J. Red thawed frozen plasma investigation. Internal report submitted to Canadian Blood Services, Edmonton. 2015. 22. Turner TR, Acker JP. Quality assessment of cryopreserved/irradiated SAGM/RBC units. Internal report submitted to Canadian Blood Services. 2015. 23. Turner TR, Acker JP. Unit investigation: O negative, Gerbich negative donor. Internal report submitted to Canadian Blood Services. 2015. Theses 1. Vadasz B. Pathogenesis of anti-integrin αIIb-mediated fetal and neonatal alloimmune thrombocytopenia: Establishment of novel murine models in αIIb deficient and Human αIIb transgenic mice. Department of Laboratory Medicine and Pathobiology. MSc. Supervisor: Ni H. University of Toronto; 2015. Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxix Appendix III: Health Canada Financial Contribution Summary of Expenditures – April 1 2015 to March 31 2016 Schedule 1: Overview Operating funds (Schedule 2) 989,251 Funding programs (Schedule 3) 5,303,212 Total $6,292,464 Schedule 2: Operating funds Centre for Innovation program administration 573,719 NetCAD operations 130,751 Intellectual property protection and other legal activities 284,782 Total $989,251 Schedule 3: Funding programs Canadian Blood Services/CIHR partnership operating grants 2,588,517 Canadian Blood Services/CIHR new investigator program 60,000 Canadian Blood Services intramural operating grants 759,076 James Kreppner fellowship in blood system studies 75,000 Small projects funding 14,296 Graduate fellowship program 415,177 Postdoctoral fellowship program 378,916 Summer internship program 84,532 Program Support Award for Canadian transfusion medicine and science research CIHR partnership: Transplantation research 691,594 50,000 Additional funding for research projects 186,104 Total $5,303,212 Notes: • Funding programs include capital expenditures under $10,000 Canadian Blood Services’ Centre for Innovation – Progress Report 2015-2016 xxx
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