Reducing the risk of Cytomegalovirus through leukocyte reduction
Guest contributor; Dr. Nadine Shehata, medical director, Mount Sinai Hospital, Toronto.
Cytomegalovirus (CMV) is a herpes family virus transmitted by direct contact early in life as well as by transfusion of cellular products. About half of Canadians have been infected by CMV by early adulthood. Primary CMV infection is followed by life-long, latent infection, often with periodic, subclinical episodes of reactivation of infection.
The most important approach to reduce the risk of CMV transmission by cellular products has been leukocyte reduction (e.g., buffy coat production method) and the administration of blood from donors who are seronegative for CMV. The need for both CMV seronegative blood in addition to leukocyte reduction is widely debated with many blood agencies offering both interventions as CMV in immune compromised individuals results in significant morbidity. A trial to determine whether leukocyte reduction and providing CMV seronegative cellular product are additive in reducing the risk to CMV transmission in comparison to only providing leukocyte reduced products would be prohibitive as there is minimal residual risk from leukocyte reduction and sample sizes to demonstrate a difference would be unattainable. This residual risk from leukoreduced products has been estimated to be comparable to the residual risk of transmission of hepatitis viruses. Seed and colleagues developed a model estimating residual risk of leukodepleted only red cell and platelet units in Australia and described a residual risk of 1 in 13.6 million, 1 in 7.8 million (95%CI: 1 in 7.7–1 in 9.9) for red cells and zero risk (95%CI: 0–1 in 1.1 million) for platelets,1 comparable to the residual risk of hepatitis C virus transmission of 1 in 12.6 million donations and hepatitis B virus transmission of 1 in 7.5 million Canadian donations.2
Previously, administration of blood from donors who were CMV-IgG seronegative was also employed as a transfusion-transmitted CMV risk reduction measure. Of note, the safety of CMV-IgG seronegative donors has also been debated, as it is CMV-DNA, not serology, that is indicative of infectivity. CMV-DNA in a study of donors was detected in plasma samples of 44 per cent of newly seropositive donors (12%-62%, depending on the time from the last seronegative donation) but not in seropositive donors who had been seropositive for at least one year, suggesting perhaps a greater risk from seronegative donors if they are exposed to CMV.3
CMV-IgG seronegative cellular products have not been requested since 2013 at Mount Sinai Hospital for pregnant individuals including many with sickle cell disease who have required red cell exchange (2-10 red cell units monthly) and for neonates including those with low birth weight and who are preterm, says Dr. Nadine Shehata, medical director of transfusion medicine laboratory, Mount Sinai Hospital, Toronto. Following the decision in 2017 to only provide CMV seronegative cellular products for fetuses requiring intrauterine transfusion in Canada, periodically cellular products that were CMV untested/positive were used for intrauterine transfusion because of the urgent need for blood. Because of the experience of not requesting CMV negative cellular products for pregnancies and neonates, recent periodic use of CMV untested/positive cellular products when urgent cellular products were needed for intrauterine transfusion and following discussions with stakeholders, the policy was changed to accept leukocyte reduced cellular products without the requirement of CMV testing for intrauterine transfusion.
Dr. Gwen Clarke, medical officer at Canadian Blood Services, adds, another important benefit of this change is an enhanced capacity to provide phenotype-matched red blood cells for the mother when selecting red cell components for intrauterine transfusion, which may prevent additional alloimmunization from red cell exposure at the time of intrauterine transfusion.
Seed CR, J, Polizzotto MN, Faddy H, Keller AJ, J Pink J. The residual risk of transfusion-transmitted cytomegalovirus infection associated with leucodepleted blood components. Vox Sang 2015 Jul;109(1):11-7. doi: 10.1111
O'Brien SF, Yi Q-L, Fan W , Scalia V, M, Fearon, MA. Residual risk of HIV, HCV and HBV in Canada. Transfus Apher Sci 2017 Jun;56(3):389-391. doi: 10.1016/j.transci.2017.03.010
Ziemann M, Krueger S, Maier AB, Unmack A, Goerg S, Hennig H. High prevalence of cytomegalovirus DNA in plasma samples of blood donors in connection with seroconversion. Transfusion. 2007; 47: 1972-1983
Assisting hospitals with optimal inventory management
The Amber Phase declared in December 2022 highlighted the need to have both complete hospital disposition and inventory data. How can the Average Daily Red Cell Demand (ADRD) and Inventory Index (II) assist hospitals with optimal inventory management during green phase (normal) operating conditions?
“In my early years as a charge technologist of transfusion medicine, Canadian Blood Services reminded me to look at blood utilization for their demand forecasting,” says Heather McMahon, Charge Technologist, Blood Transfusion, Laboratory Services, Royal Victoria Regional Health Center in Barrie, Ontario. When the Ontario Regional Blood Coordinating Network’s (ORBCoN) inventory calculator tool was introduced, I used this to determine the target inventory red blood cell levels (green phase) and those required in amber or red phase of our Emergency Blood Management Plan on a yearly basis using my most recent 12-month disposition. It is easy to use and accurate. The current version provides estimated target levels for one, two, five, eight and 10-day inventory stock levels.
Prior to our Canadian Blood Services/Ontario Regional Blood Coordinating Network (ORBCoN) site visit in November 2022, I reviewed the disposition data they provided and noted a decrease in red blood cell utilization in 2021 from the previous two years. The inventory calculator tool was used, and our inventory levels were adjusted. There was a notable reduction from a total of 111 to 101 red blood cells for our routine stock. In determining levels, I also take into account the distance we are from our Canadian Blood Services distribution site (86 km), especially for our stock of group O negative red blood cells, the number of units outdated, the number of routine deliveries per week and noting that we are the regional hospital in our area that may supply blood to other sites in emergencies considering how long a STAT delivery may take.
The National Emergency Blood Management Committee (NEBMC) uses disposition data and daily inventory levels that hospitals submit to Canadian Blood Services to understand the current state of both hospital and Canadian Blood Service inventory during a declared inventory shortage phase, like the recent Amber Phase. To calculate ADRD (red blood cells transfused + wasted ÷ 365 days) for a given hospital, Canadian Blood Services requires 12 current and consecutive months of red blood cell disposition data. To calculate the Inventory Index (current inventory ÷ ADRD) Canadian Blood Services needs a current inventory level submission and the ADRD. If a hospital is not up to date with either disposition or inventory submission, these markers cannot be calculated and then reviewed to understand whether a current inventory phase will continue or move to another phase (into Red or into Recovery). Lack of disposition and inventory data from some hospital customers in several provinces was identified as a gap for the NEBMC. Keeping disposition submissions current, and reporting inventory on a regular basis, and as directed by the Amber Phase Advisory, allows a hospital to practice timely inventory review and update based on a hospital’s own data, as illustrated in the example above.
The 18th Annual Transfusion Medicine Education Symposium
Hosted by Canadian Blood Services and the Ontario Regional Blood Coordinating Network (ORBCoN), the symposium is designed to enhance the transfusion skills of healthcare professionals working in community hospitals, with a focus on improving patient outcomes. We invite physicians, nurses, technologists, residents, trainees and students involved in the ordering, issuing or transfusing of blood and blood products to attend.
"While a lot of attention in transfusion medicine is rightly paid to red blood cells (typing, antibody screening, crossmatching), for this year's symposium we wanted to spotlight the 'supporting cast' of blood products: fibrinogen replacement, platelet concentrates, and plasma. These products play an important role in effectively managing bleeding (or preventing it from developing in the first place). Experts will discuss modern use of these products and provide updates about an evolution underway at Canadian Blood Services. Our goal is to improve familiarity with the clinical use of these products and what efforts are being made to improve their safety” says Dr. Johnathan Mack, Canadian Blood Services Medical Officer and co-chair of the symposium organizing committee.
The symposium will feature presentations from Dr. Michelle Zeller of McMaster University on pathogen-reduced platelets, Dr. Andrew Petrosoniak of Sunnybrook Health Sciences Centre on fibrinogen replacement, and Dr. Kathryn Webert of Canadian Blood Services on solvent detergent plasma.
Registration for this virtual event is free. The symposium is accredited for Continuing Medical Education by the Royal College of Physicians and Surgeons of Canada and the College of Family Physicians of Canada.
In addition to the morning and afternoon sessions on April 27, we are pleased to offer a technical workshop for Ontario Transfusion Medicine laboratories. Registration is required by March 20, 2023, to receive the case materials. The case review discussions will be held on Wednesday April 26. Please visit Upcoming Events – Transfusion Ontario for registration.
Learn about the 4 FARES2 and FIIRST2 clinical trials
There are two clinical trials underway that may be of interest to our subscribers. The outcome of both clinical trials could influence future use and demand for frozen plasma and are scheduled to be completed in late 2024.
The first clinical trial compares the hemostatic treatment response to 4-factor prothrombin complex concentrate (Octaplex) with frozen plasma in patients undergoing cardiovascular surgery (FARES-2). The trial is being conducted in Canadian and US sites and is partially-funded by the Canadian Institutes for Health Research (CIHR). Enrollment opened in October 2022 with a target of approximately 500 patients and is expected to conclude in October 2024. Depending on the risk-benefit profile of the two therapies, there could be a decreased demand for frozen plasma in the future for patients having this type of surgery. The Canadian hospitals participating are the Royal Columbian Hospital, Vancouver General Hospital, Kingston General Hospital, London Health Sciences Center, Hamilton Health Sciences, Sunnybrook Health Sciences Center, Unity Health - St. Michael’s Hospital, University Health Network -Toronto General Hospital, The Ottawa Hospital, Montreal Heart Institute, and Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval. The American hospitals participating are Duke University and the Oklahoma Health Sciences Center.
The second clinical trial of interest is called Factors in the Initial Resuscitation of Severe Trauma 2 (FiiRST–2). This clinical trial compares prothrombin complex concentrate plus fibrinogen concentrate with standard massive hemorrhage protocol with frozen plasma in trauma patients at risk of massive hemorrhage to determine if it will lead to superior patient outcomes. This clinical trial is partially-funded by the Canadian Institutes for Health Research (CIHR). Canadian hospitals participating in this clinical trial include Vancouver General Hospital, Sunnybrook Health Sciences Center, Hamilton Health Sciences Center, London Health Sciences, and St. Michael's Hospital. The study is estimated to close in January 2024.
New digital resource hub for stem cell patients and families
The wait for a matching stem cell donor is always difficult, and each patient and family copes with it in their own way. In some cases, people choose to actively recruit new potential donors for our stem cell registry during that time. And while it is very unlikely that a patient would ever recruit their own unrelated match — and patients in Canada are certainly not expected to find their own stem cell donors — these families know their efforts can bring hope to all those waiting for transplants, now and into the future.
That is why we have launched some new digital resources for those patients and families. Our new digital hub will support them to:
host their own recruitment drive
share their story with us
engage news media and use social media effectively
run a “recruit-and-raise” campaign
You can use social media to share the two patient stories already available in the hub, and watch that page for new ones. You can also engage your followers with the hashtag #StemCellsForLife and tag us @CanadasLifeline. Also, tag your followers and encourage them to do the same using the same hashtag.
Dr. Siobhan Deshauer has seen firsthand the importance of donated blood. She’s given medications made from plasma, a component of blood, to many of her own patients. And it made her wonder: What is it like to donate blood? And what exactly happens to blood donations on their way to saving lives?
It seemed like the perfect topic for her YouTube channel, Violin MD, where Dr. Deshauer gives her over 900,000 followers an inside look at the world of medicine (sometimes accompanied by violin, which she played professionally before becoming a doctor).