Transfusion Medicine Community Research Articles

Examining Injustices: Transfusion Medicine and Race

Race and ethnicity are sociopolitical and not biological constructs, and assertions that these population descriptors have scientific meaning has caused significant harm. A critical assessment of the transfusion medicine literature is an important aspect of promoting race-conscious as opposed to race-based medicine. Utilizing current definitions and health equity frameworks, this review will provide a critical appraisal of transfusion medicine studies at the intersection of race and healthcare disparities, with a focus on larger methodological challenges facing the transfusion medicine community. Moving forward, risk modelling accounting for upstream factors, patient input, as well as an expert consensus on how to critically conduct and evaluate this type of literature are needed. Further, when using race and ethnicity in research contexts, investigators must be aware of existing guidelines for such reporting.

Hepatitis E virus as a transfusion transmitted infection-current status

Objectives: Hepatitis E virus (HEV) infection is growing worldwide and presents a new threat to the blood transfusion services across the world. The present review tries to explore how the transfusion medicine community is responding to the threat. Materials and Methods: The major papers and important case reports were culled from PubMed, Science Direct, Embase related to this infection, and transfusion medicine since 2005 were explored and relevant articles were discussed with emphasis on epidemiology, infection, prevalence in donor population, susceptible recipients, prevention, and future development. Results: There are eight genotypes of this virus with different host, transmission biology, and clinical infection. Chronic infections are more common with Genotype 3 and Genotype 4 which are prevalent in Europe and transmitted by pig and meats cooked from this animal. Genotype 5 and 6 has not yet been linked to human transmission. Genotype 1 and Genotype 2 cause epidemic form of this infection and are common in developing countries. Immunosuppressed and chronic liver disease patients get chronic or severe infection. Pregnant ladies develop fulminant hepatitis with high mortality. The virus is transmitted by blood products but severe infection is uncommon. Many European countries, USA, Canada are using Nucleic Acid Testing (NAT) based technology to screen their donors as Individual Donor-NAT or Minipool NAT with varying efficiency. Large part of the world as yet has not taken any active measure to contain this infection through transfusion. A vaccine is available, effective but is not widely used as more studies are needed. Cross immunity does happen between genotypes and presence of immunoglobulin G antibody in blood protects against serious infection. Alanine transaminase level corresponds with viremia in asymptomatic but infected individuals. Conclusion: The HEV is an emerging but important threat to transfusion medicine service. Important information regarding this infection is still lacking. However, there is a need to develop robust safety algorithm to counter this threat and make transfusion safer.

From MPOX to the next epidemic: Words matter when talking about equity-deserving groups.

From MPOX to the next epidemic: Words matter when talking about equity-deserving groups.

Survey of blood centre readiness regarding removal of DEHP from blood bag sets: The BEST Collaborative Study.

Di(2-ethylhexyl) phthalate (DEHP) must be removed from blood bag sets in Europe by 27 May 2025. DEHP is known to interact with the red blood cell (RBC) membrane, resulting in reduced haemolysis and thus prolonging shelf-life. Current non-DEHP alternatives result in increased haemolysis requiring reconsideration of the RBC shelf-life. Although the immediate impact of eliminating DEHP is to the European community, the non-DEHP movement could affect blood bag set availability globally. The purpose of this survey is to understand blood centre readiness regarding the transition to non-DEHP blood collection and storage systems. A 24-question on-line survey was completed by members of the Biomedical Excellence for Safer Transfusion Collaborative research network. Responses were obtained from 16 blood collection or processing institutions. A majority of respondents (12/16) indicated that both shelf-life and haemolysis were equally important in selecting non-DEHP blood bag sets. Six respondents would accept a lower RBC product shelf-life compared to current practice. Respondents were not clear on the best non-DEHP vinyl material or RBC storage solution. Three European blood centres indicated they have developed non-DEHP transition plans. One challenge identified regarding the transition to non-DEHP is the extensive validation testing that will be required. Blood centres in Europe are concerned with meeting the sunset date for DEHP, considering that limited non-DEHP blood bag and RBC storage solutions are currently available. Banning DEHP in Europe, which may have global ramifications, represents a major challenge not yet fully understood by the transfusion medicine community.

Low prevalence red blood cell antigens: transfusions, babies, and changing demographics

See article on page 870–874, in this issue

Transfusion in limited infrastructure locations – where to go decades after safe blood initiative by World Health Organization?

Transfusion demand in sub‐Saharan Africa is increasing. Establishment of large national blood services seems to be challenging. Hospital blood services maintain the basic supply. However, they lack effective communication networks. Cell phones/internet provides the infrastructure for establishing such networks and could help in establishing haemovigilance systems. Voluntary non‐remunerated donors are the minority of donors (<20%). It seems more appropriate to develop strategies to increase the safety of replacement donor blood instead of insisting on copying Western‐world models. Red cell serology is usually restricted to ABO/Rh‐D and at best Coombs crossmatch. Introduction of antibody differentiation and additional typing for C,c,E,e and K would prevent 60–70% of delayed haemolytic transfusion reactions. One of the most frequent indications for blood transfusion is major haemorrhage. Why is component therapy still recommended for resource‐limited regions, while whole blood is reintroduced in Europe/US for exactly the same indications? Plasma thawed due to electricity failures is usually discarded anyway. Leuco‐depleted products would be beneficial (multitransfused sickle‐cell patients/neonates/AIDS). An ideal blood product could be whole blood, in‐line leuco reduced by gravity filtration, treated by user‐friendly pathogen‐reduction not requiring irradiation/illumination. The transfusion medicine community should form an alliance to develop an affordable, pathogen‐reduced blood product, to train regional auditors and to bring in external expertise to aid knowledge transfer. However, standards to be reached should be defined by the respective national experts who understand the culture and needs of their country. In respectful collaboration, we could learn from each other to finally improve transfusion in resource‐limited regions.

In Memoriam: Kenji Tadokoro, MD, PhD: 1947 - 2018

Kenji Tadokoro was born on 14 April 1947 in Sapporo, Japan. He graduated from Tokyo University School of Medicine in 1973. He worked as a senior resident and subsequently a research associate in the Department of Medicine and Physical Therapy of Tokyo University Hospital from 1973 to 1981, focusing his research on the mechanisms of allergic reactions. From 1981 to 1984, Kenji was a Research Fellow, Institute of Clinical Immunology at the University of Bern, Switzerland. He returned to Japan in 1984 as a Research Associate in the post-graduate Division of the School of Medicine at the University of Tokyo and Tokyo University Hospital where he earned his PhD degree in 1992. In 1992, he joined the Japanese Red Cross (JRC) Central Blood Center in Tokyo as the Director of Research. Since then he worked diligently on improving donor screening systems for infectious diseases within the JRC and internationally including establishing the hemovigilance department in 1993. He served as an Executive Officer since 2004 and was appointed Chief Executive Officer for Blood Services in 2014, which he retained until early 2017. Although he made many other contributions in the areas of blood services management, transfusion-related GVHD and hemovigilance, Kenji's career was highlighted by his leadership in the rational introduction of new donor screening assays, focusing on the introduction of nucleic acid testing (NAT). Step by step, based on modelled projections, pilot studies and observed yield, he advanced on-going implementation and demonstrated the efficacy of NAT, which successfully decreased the risk of transfusion-related HIV, HBV and HCV in Japan. The hemovigilance department he established, includes a large specimen repository, likely the largest in the world, enabling unique look-back studies confirming transfusion transmission, documenting their rates and establishing correlates and linkage to disease outcomes. The programme has shown the importance of a comprehensive blood testing and patient outcome system in improving blood safety. He has published over 100 peer-reviewed articles informing the global transfusion medicine community of the implications of the JRC research findings. Kenji enthusiastically nurtured warm relationships with international colleagues engaged in blood programmes. He invited staff from many Asian countries to JRC for training and was instrumental in convening Red Cross and Red Crescent symposia in the Asian region every three years. He chaired the Asia Pacific Blood Network for four years until 2017 and also held the position of Zone Coordinator of the Global Advisory Panel of Blood Services in Red Cross and Red Crescent Societies. He was a very active member of the AABB and ISBT and other related societies (IPFA/PEI), attending many Congresses and participating in numerous working parties and committees. Through these activities, he continued to express the opinions of an Asian country both scientifically and related to policy. Kenji resigned as CEO of JRC in 2017 due to health reasons and assumed a special senior advisor role for the JRC blood programme. Kenji passed away on 20 October 2018. Those who knew him will cherish his memory as a man of integrity, earnestness and kindness, and a great leader of the JRC and international community. He was a friend and cherished colleague; his wisdom and fellowship will be sorely missed.

Systems biology as an emerging paradigm in transfusion medicine

Blood transfusions are an important part of modern medicine, delivering approximately 85 million blood units to patients annually. Recently, the field of transfusion medicine has started to benefit from the “omic” data revolution and corresponding systems biology analytics. The red blood cell is the simplest human cell, making it an accessible starting point for the application of systems biology approaches.In this review, we discuss how the use of systems biology has led to significant contributions in transfusion medicine, including the identification of three distinct metabolic states that define the baseline decay process of red blood cells during storage. We then describe how a series of perturbations to the standard storage conditions characterized the underlying metabolic phenotypes. Finally, we show how the analysis of high-dimensional data led to the identification of predictive biomarkers.The transfusion medicine community is in the early stages of a paradigm shift, moving away from the measurement of a handful of chosen variables to embracing systems biology and a cell-scale point of view.

Blood-Borne Pathogens: A Canadian Blood Services Centre for Innovation Symposium.

Testing donations for pathogens and deferring selected blood donors have reduced the risk of transmission of known pathogens by transfusion to extremely low levels in most developed countries. Protecting the blood supply from emerging infectious threats remains a serious concern in the transfusion medicine community. Transfusion services can employ indirect measures such as surveillance, hemovigilance, and donor questioning (defense), protein-, or nucleic acid based direct testing (detection), or pathogen inactivation of blood products (destruction) as strategies to mitigate the risk of transmission-transmitted infection. In the North American context, emerging threats currently include dengue, chikungunya, and hepatitis E viruses, and Babesia protozoan parasites. The 2003 SARS and 2014 Ebola outbreaks illustrate the potential of epidemics unlikely to be transmitted by blood transfusion but disruptive to blood systems. Donor-free blood products such as ex vivo generated red blood cells offer a theoretical way to avoid transmission-transmitted infection risk, although biological, engineering, and manufacturing challenges must be overcome before this approach becomes practical. Similarly, next generation sequencing of all nucleic acid in a blood sample is currently possible but impractical for generalized screening. Pathogen inactivation systems are in use in different jurisdictions around the world, and are starting to gain regulatory approval in North America. Cost concerns make it likely that pathogen inactivation will be contemplated by blood operators through the lens of health economics and risk-based decision making, rather than in zero-risk paradigms previously embraced for transfusable products. Defense of the blood supply from infectious disease risk will continue to require innovative combinations of surveillance, detection, and pathogen avoidance or inactivation.

Zika virus and the never-ending story of emerging pathogens and transfusion medicine.

In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine.

The transfusion‐related acute lung injury controversy: lessons from heparin‐induced thrombocytopenia

The transfusion‐related acute lung injury controversy: lessons from heparin‐induced thrombocytopenia

Emerging and imported infections in the region – what's bothering us today?

An emerging infection is defined as one that has appeared in a population for the first time, or that may have existed previously but is rapidly increasing in incidence or geographic range. The Asia Pacific region, with 30% of global population, has a reputation as a hot spot for emerging infections. The emergence of severe acute respiratory syndrome exactly 10 years ago dramatically transformed individual and national awareness and capabilities for identifying and responding to regional emerging infectious threats. The impact of emerging infections on the blood supply may be direct through the potential for transmission through transfusion, the effect on blood donor attendance and eligibility and the effect on blood demand. There is a need for constant surveillance and the capacity to identify, assess and manage risks to the blood supply. In recent years, the strengthening of regional and international partnerships and the development of new risk assessment tools has improved our ability to respond to infectious threats. Nonetheless, the volatile and ever‐changing nature of emerging infections will remain a constant challenge to the vigilance and response capabilities of the transfusion medicine community.

Tranexamic acid: more evidence for its use in joint replacement surgery

Tranexamic acid: more evidence for its use in joint replacement surgery

Costs and benefits of PAS platelets: A mix of science, quality, and value

Costs and benefits of <scp>PAS</scp> platelets: A mix of science, quality, and value

Predominance of HBsAg (+ve) and Anti-HCV Positivity among Blood Donors: Experience in a Private Hospital of Dhaka, Bangladesh

Background: Hepatitis B and C virus infection in Bangladesh continues to be a public health problem for the last few decades. Transfusion related hepatitis is a major concern among the transfusion medicine community in Bangladesh. Objectives: This study was conceded out to characterize the security profile of Bangladeshi healthy blood donors and to point out the importance of screenings programs that must be applied, and also patterns of virus positivity among different age & sex groups were determined. Patients and methods: Through out this study we reviewed the testing records of 3048 healthy blood donors (Male-2680 and Female-368) who presented by random at blood bank’s records from January 1st, 2010 to December 31st, 2010 at a private Hospital in Dhaka, Bangladesh. All the samples were examined using 3rd generation enzyme linked immunosorbant assays for Anti-HCV and HBsAg (+ve) detection. Statistical Analysis was done using standard procedure. Results: The study found the overall predominance of HBsAg (+ve) was 1.24% and Anti-HCV was 0.17%. Predominance of co-infection with HBV and HCV was 0.00%. Conclusions: Impact of this paper will help to provide information on the current risks of blood transfusion in Bangladesh thus to advice of alternatives to transfusion can mitigate some of those concerns now and near future.

How do I provide leukapheresis products? Blood center experience and evidence for process improvement

The past few decades have seen a resurgence of interest in leukapheresis products to improve the survival of infected patients with neutropenia. These products have a short shelf life and require donor stimulation with dexamethasone before collection. Additionally, a system with good communications and logistical support is essential. A recent survey of blood centers in North America revealed that the majority of centers collecting leukapheresis products use steroid-stimulated donors. The survey results suggested that an analysis of the process and potential process improvement would be of interest to the transfusion medicine community. Data from 2008 to 2011 regarding donor selection, donor dexamethasone stimulation, leukapheresis collection, and correlations between potentially pertinent variables for process improvement were analyzed. Results from an analysis of cost are also included. We evaluate 432 leukapheresis donations and demonstrate correlations between 1) pre- and poststimulation white blood cell (WBC) count (p<0.0001), 2) interval (donor stimulation to collection) and poststimulation WBC count (p<0.0001), and 3) poststimulation WBC count and leukapheresis product granulocyte yield (p<0.0001). Significant improvement in granulocyte quality and yield can be accomplished in dexamethasone-stimulated donors, by selecting eligible donors with relatively high normal prestimulation WBC counts and/or previously good responses to dexamethasone, increasing the duration between dexamethasone stimulation and granulocyte collection, and maintaining optimal hematocrit (5%-10%) in granulocyte collections. Because the majority of surveyed blood centers collecting stimulated granulocytes use steroids alone, modifications presented here may prove useful. Further assessment of correlation between granulocyte yield and clinical outcome will await results of additional studies.

Chagas disease: a threat to safe blood transfusion

Chagas disease affects approximately 8 million infected people in Mexico and Central and South America and causes 12 500 deaths annually; 41 200 new cases are reported annually (2006). Coordinated multicenter programmes have decreased about 70% of new infections in South America due to the interruption of vectorial and decreased blood transfusion transmissions. Migration of the infected population from rural areas to urban centres in endemic and non‐endemic countries led to the urbanization and globalization of Chagas disease. Chagas disease is now an emerging disease in non‐endemic areas, where congenital, blood and organ transplant transmissions are associated with reactivation of chronic Chagas disease in patients under immunosuppression or HIV infection. Recent initiatives in non‐endemic countries have been implemented to control its transmission by blood transfusion and transplants of organs. Most of the infected people were asymptomatic individuals in the chronic phase of the disease, characterized by and low and intermittent parasitemia and diagnosed by serological tests. In endemic countries, universal mandatory screening tests for detection of Trypanosoma cruzi antibodies dramatically reduced blood transfusion transmission. In non‐endemic countries, where transfusion represents the most important way of transmission, different strategies have been registered: (1) blood donor selection and deferral; (2) blood donation testing; (3) blood donation testing in people who lived in endemic areas. Questionnaires containing well‐defined questions help to identify patients from endemic areas and their epidemiological data but are of limited value since they depend on donor information. High‐performance serologic tests were reported for the detection of anti‐T. cruzi antibodies like ELISA with epimastigotes or trypomastigotes or recombinant antigens, chemiluminescent, immunoblot and radioimmunoprecipitation assays. Almost 100% of sensitivity and specificity were registered when tested in samples of well‐defined chronic chagasic patients but gold standards are not validated in circumstances of low prevalence of the disease. Additionally, their value in cases of inconclusive results (one positive test and other negative or doubtful results) was not known. Unfortunately, molecular methods are less sensitive than serology for the chronic phase of the disease (45–100% sensitivity) and were not reliable for screening tests in blood banks. Perspectives of the reduction of parasites by photochemical treatment and ultraviolet (crystal violet, methylene blue, amotosalen, riboflavin, thiopirilium) were reported sometimes with slight changes in the blood products. However, the main challenge is to demonstrate their value for prevention of a broad spectrum of agents transmitted by blood transfusion (including príon disease) and inactivation of low parasite load. In summary, questionnaires including specific questions about donor epidemiology and high‐performance serologic tests have been useful for blood bank screening. The cost–benefit–effectiveness analyses of universal serologic screening vs. serologic screening of selected donors depend on the prevalence of positive donors and should be evaluated in different regions. Finally, as pathogen inactivation methods may represent remarkable improvement in blood bank transfusion, efforts from the academia are necessary to prove their safety and effectiveness, and from blood banking–transfusion medicine community and public regulators to their implementation aiming to increase the safety of blood transfusion for patients around the world.

Treatment of whole blood with riboflavin plus ultraviolet light, an alternative to gamma irradiation in the prevention of transfusion‐associated graft‐versus‐host disease?

Exposure of blood products to gamma irradiation is currently the standard of care in the prevention of transfusion-associated graft-versus-host disease (TA-GVHD). Regulatory, technical, and clinical challenges associated with the use of gamma irradiators are driving efforts to develop alternatives. Pathogen reduction methods were initially developed to reduce the risk of microbial transmission by blood components. Through modifications of nucleic acids, these technologies interfere with the replication of both pathogens and white blood cells (WBCs). To date, systems for pathogen and WBC inactivation of products containing red blood cells are less well established than those for platelets and plasma. In this study, the in vitro and in vivo function of WBCs present in whole blood after exposure to riboflavin plus ultraviolet light (Rb-UV) was examined and compared to responses of WBCs obtained from untreated or gamma-irradiated blood by measuring proliferation, cytokine production, activation, and antigen presentation and xenogeneic (X-)GVHD responses in an in vivo mouse model. In vitro studies demonstrated that treatment of whole blood with Rb-UV was as effective as gamma irradiation in preventing WBC proliferation, but was more effective in preventing antigen presentation, cytokine production, and T-cell activation. Consistent with in vitro findings, treatment with Rb-UV was as effective as gamma irradiation in preventing X-GVHD, a mouse model for TA-GVHD. The ability to effectively inactivate WBCs in fresh whole blood using Rb-UV, prior to separation into components, provides the transfusion medicine community with a potential alternative to gamma irradiation.

How Can the Blood Transfusion Medicine Community Contribute to Public Health in Tough Economic Times?

the major source of the residual risk of transfusion-transmitted infections. The rates and characteristics of these infections inform decisions about further safety interventions. These data can also validate and supplement public health surveillance; for example, the real-time tracking of largely asymptomatic donor West Nile virus infections, with coverage of the entire country, often provides the earliest evidence of human activity in a region. In this issue of the Journal of Infectious Diseases, 2 articles add to the body of information generated through analysis of sample repositories from blood donors. These studies suggest that we may be underusing the resource that donors represent for the study of infectious diseases in the United States and globally. Even before the recent H1N1 pan

The journal in PubMed and the lessons of the SciELO/Fapesp seminar on journal performance

The third seminar, coordinated by SciELO and Fapesp, on the evaluation of the performance of Brazilian journals took place in September in Sao Paulo. With the editors of most of the Brazilian journals linked to SciELO and Fapesp attending, the contribution of these two institutions was demonstrated in the event, as was the promising results observed since the first meeting held three years ago. It was reported that there has been an increase in the number of journals published in English. In the SciELO database, for example, the proportion increased from 33% to 66% over three years and the progress of Brazil in the indexation of journals in the JCR/ISI/Thomson Reuters has been very expressive. The increase in Brazilian scientific production with indexation of journals in the World of Science (WOS) of Thomson Reuters since 2005 is shown in Figures 1 & 2(1). Figure 1 2005-2010: Countries that added over 40 titles to Web of Science Figure 2 2005-2010: Clinical medicine - countries with greatest increase in coverage For the first time in the area of health sciences, Brazilian journals have an Impact Factor (IF) higher than two and there is an increasing number of journals with IFs higher than one or that are close to this value. In the event, the Editor-in-Chief of the journal Frontiers in Ecology and the Environment, Sue Silver gave a speech on the theme Scientific journals: raising profiles, prospects and Impact Factors. With her experience with the implantation of the journal The Lancet Oncology, Sue Silver listed the different measures that enabled her as editor of Frontiers in Ecology and the Environment to index the journal in the WOS in 2003 and to attain an IF of 3.32 by 2005; the current IF is 9.113. This IF is very high for medical journals. The magic formula to achieve this, as described by the Editor-in-Chief, is simply based on a professional organization of the journal, work and dedication at all levels of the editorial process and attaining a high-level of consultancy in the editorial, internal and marketing boards with the goal of deploying a judicious evaluation of the high-level scientific contributions that will be published. Sue Silver cited strategies on how to attract good authors and thus good papers for publication in the Frontiers in Ecology and the Environment. With this, the articles started to be cited and as a result there was an exponential increase in the IF as previously mentioned. This apparently trivial measure (that is difficult for some scientific institutions to understand) put Frontiers in Ecology and the Environment in second place of all journals in the area of environmental sciences worldwide. The Ecology Society of American that publishes the pleasant modern looking 'Frontiers in Ecology and the Environment' also publishes several other journals available both in print and on electronic media including with the use of new tools to access issues such as iPad. Subsequently, in the SciELO/Fapesp meeting, several editors commented on their experiences and it became perfectly clear that indexation by JCR/ISI/Thomson Reuters and obtaining an IF is the Holy Grail of publishing, of scientific production and of the evaluation of researchers, especially in Brazil(2). However, several publications have shown that the IF is not a good instrument to evaluate researchers and even the editor of Science has shown strong doubts in relation to this bibliometric index(2-5). With all the hype mixed with the excessive patriotism of a large country and of an emerging country expressed in the event, the Revista Brasileira de Hematologia e Hemoterapia has learned and followed the strategies of specialty journals that are less favored by funding agencies and by CAPES(7). Even with the difficulties of a scientific journal that relies on its own finances, it is necessary to learn from the lessons of this and previous events: to overcome barriers, organize the journal's structure, to prepare a fearless and dedicated editorial staff, to expand the editorial board with international members, to start to publish in English and after two years in Lilacs, ExtraMed Scopus and SciELO become indexed in PubMed thereby giving definitive and international visibility to articles(8-11). We consider this moment in the history of the journal to be an extremely special, but emblematic, one as achieving indexation in PubMed should just be considered another step in the evolution of the journal, a step that gives a greater degree of responsibility to the hematology and transfusion medicine community as a whole. We have an obligation to maintain the scientific journal and modernize it in order to adapt it for the culture shock that has already arrived with developments in electronic media and new manners to access and divulge journals. We are only at the start.