Research Units

Infusion pumps are mechanical devices commonly used in transfusion medicine. Originally designed to assist in the delivery of fluid resuscitation products like crystalloids, infusion pumps have also come to be used in the transfusion of blood products as they can offer benefits to both patients and health-care teams. These benefits can include greater consistency and calculation of flow rate, increased accuracy of infusion volume, increased flexibility in transfusion speed in outpatient settings, and decreased risk of errors compared to gravity-based infusions. However, the growing use of infusion pumps has raised questions about the risk of mechanical damage to red blood cells (RBC).  

Health-care facilities that use these pumps rely on manufacturers and regulators to determine whether specific models are approved for infusing red blood cells. There is a lack of literature available to help guide evaluation of infusion pumps for this use and to understand the effects of different conditions, rates, and pump types on the quality of RBCs. Research providing clear evidence on the effect of infusion pumps on RBCs can be valuable to regulators, manufacturers, and health-care facilities responsible for evaluating pump safety for transfusions.  

Screening blood donors to determine their eligibility to donate is an important layer of safety within the blood system. To screen prospective donors, blood operators use a donor questionnaire (DQ) that asks questions about potential exposure to infections that could be transmitted via transfusion to recipients. With the current DQ used in Canada, men are deferred from donating blood for three months since the date of their last sexual contact with a man. This screening approach has been criticized for being discriminatory. Despite incremental changes in recent years, these time-based donor eligibility criteria still exclude many sexually active gay, bisexual and other men who have sex with men (gbMSM), including some trans, non-binary and other gender diverse people, and do not consider an individual donor’s risk of exposure to sexually transmitted infections, regardless of sexual orientation. In late 2021, Canadian Blood Services filed a proposal with its regulator, Health Canada, to use an alternative approach to screen donors. If approved, questions that ask about men having sex with men will be replaced with gender neutral, sexual behaviour-based screening questions asked of all donors. This study assessed the approach’s feasibility by exploring: 

1. How donors understand proposed alternative sexual behaviour-based screening questions; 
2. How acceptable they think the questions are; and 
3. How comfortable they feel answering them.  

Whole blood transfusion is receiving renewed interest as a lifesaving alternative to component therapy for actively bleeding patients. In Canada, all blood products for transfusion must be leukoreduced. Leukoreduction removes white blood cells that could potentially cause infectious disease transmission or unwanted immune responses. Canadian Blood Services is evaluating a platelet-sparing filter to prepare leukoreduced whole blood for transfusion. The manufacturers of the platelet-sparing filter licensed for use in Canada recommend that whole blood be filtered within eight hours of collection. This is not always operationally feasible, especially in Canada where distances between collection and processing sites can be large. This research examined whether the whole blood collection bag, leukoreduction filtration, and the timing of filtration significantly affects whole blood quality during 21 days of cold storage. Exploring and validating alternative processing parameters, such as longer hold times before leukoreduction, could offer greater operational flexibility for blood operators.

With a constant focus on maintaining a safe and adequate supply, Canadian Blood Services is committed to making blood donation as inclusive as possible. Currently, men can donate blood if it has been more than three months since their last sexual contact with a man. This is the latest in a series of progressively shorter time-based deferrals: from an indefinite deferral introduced in the mid-1980s, to a 5-year deferral (2013), a 12-month deferral (2016), and now a 3-month deferral (2019). These eligibility changes have been supported by significant advances over the past three decades including better testing for transfusion-transmissible infections, the introduction of information technology systems to safely manage blood inventory and a better understanding of behaviours that expose individuals to new infections. Before and after the implementation of each change in the eligibility criteria, the safety of the blood supply and donors’ observance of eligibility criteria were evaluated. Each evaluation indicated that the risk of HIV remained very low. This study looked at trends by assessing the residual risk of HIV and donor survey results between 2010 and 2021, a period encompassing all three eligibility criteria changes.

Albumin is a human protein purified from the plasma of thousands of blood donors. Since the 1960’s, it has been popular for fluid resuscitation in different patient groups, including cardiac surgical patients, who tend to require large volumes of fluid around the time they undergo surgery. Electrolyte solutions called crystalloids, which are not derived from blood, can also be used as part of a fluid management strategy but it is unclear if supplementation of crystalloids with albumin is beneficial in treating blood loss. This research examines whether there are advantages to albumin use in bleeding cardiac surgical patients, a group at high risk for serious complications who often receive blood products.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a new, rare clotting disorder associated with administration of adenoviral vector vaccines against COVID-19 (e.g., ChAdOx1 nCoV-19, AstraZeneca). VITT causes moderate to severe thrombocytopenia (low platelet levels) and thrombosis (formation of blood clots) that mimics the response observed in patients with heparin-induced thrombocytopenia (HIT).

HIT occurs when immunoglobulin G (IgG) antibodies recognize novel epitopes (antibody binding sites) exposed after heparin binds to a platelet protein called platelet factor 4 (PF4). The antibodies bound to the PF4-heparin complex form an immune complex which activates platelets (by binding to a platelet receptor called FcgRIIa) and promotes clot formation. One idea is that VITT has a similar pathophysiology to HIT but without dependence on heparin. This study aims to better understand the mechanism behind clot formation observed in VITT patients.

Convalescent plasma (plasma collected from individuals who have recovered from an infection) has historically been used to treat various diseases, including SARS-CoV-1, MERS-CoV, and influenza. At the onset of the COVID-19 pandemic, convalescent plasma from individuals who had recovered from COVID-19 stood as a potential antibody-based treatment for patients. However, there was insufficient evidence at the time on the safety and risks of COVID-19 convalescent plasma (CCP). In May 2020, the CONCOR-1 trial was developed to explore CCP as a potential treatment for patients with COVID-19. This Canadian-led international clinical trial compared convalescent plasma and standard-of-care for hospitalized adults with acute COVID‑19 respiratory illness requiring supplemental oxygen.

Vaccination with an adenoviral vector vaccine against COVID-19 (i.e., ChAdOx1 nCoV-19, AstraZeneca) has been associated with a rare clotting disorder that has become known as vaccine-induced immune thrombotic thrombocytopenia (VITT). The clotting disorder develops when IgG antibodies recognize a platelet protein (PF4), forming a PF4-polyanion complex, which strongly activates platelets. This leads to a decrease in the number of platelets (platelet consumption) and promotes clot formation.  

Little is known about treating patients with VITT. The recommendation to use high-dose intravenous immune globulin (IVIG) to reduce platelet activation is based on the observation that VITT strongly mimics autoimmune heparin-induced thrombocytopenia (HIT) (even though patients with VITT usually have not received the anticoagulant heparin). For HIT, IVIG can be an important adjunct treatment. 

This report describes three Canadian patients who developed VITT after receiving the AstraZeneca vaccine. Using a newly developed diagnostic test for VITT, researchers documented the inhibition of platelet activation after treatment with IVIG in these three patients.

Platelet transfusion is an essential and very common aspect of supportive care for children with cancer. Previous literature suggests that 52% of all children with cancer will receive a platelet transfusion during treatment. Much of platelet transfusion practice for children is based on adult studies, although children may have a higher risk of bleeding and increased harm compared to adults. Data on children are lacking on the frequency of transfusions, how low the platelet count would have to be before a doctor orders a transfusion (pre-transfusion thresholds), what a normal response to transfusion is, as measured by the change in platelet count (post-transfusion increments), and the rate of platelet transfusion refractoriness (PTR). PTR, generally defined as repeated failure to achieve satisfactory responses to platelet transfusions, can be due to immune (e.g., presence of antibodies to platelet antigens that are not found on the child’s platelets) or nonimmune (e.g., infection) causes and can be associated with harmful outcomes like increased bleeding risk.

The objectives of this study were to: (1) Describe platelet transfusion practice for children with malignancy; (2) Determine the normal platelet increment following platelet transfusion and, (3) assess the rate of PTR (platelet increments ≤ 10 x109/L following two or more consecutive platelet transfusions).

During cardiac surgery patients may experience a disruption in their coagulation system (ability to form blood clots). This causes excessive bleeding. Managing bleeding and improving clotting in these patients requires that insufficient levels of an enzyme called thrombin, which helps form blood clots, be replenished.

A number of clotting factors need to be present in blood to improve thrombin generation. Frozen plasma (FP), which contains clotting factors, is used in Canada to manage clot formation in cardiac patients despite the lack of data supporting its effectiveness and risk of causing adverse transfusion reactions, particularly heart failure. Prothrombin complex concentrates (PCCs), which contain selected clotting factors, may be a potential alternative to FP in the management of bleeding. PCCs have multiple advantages since they do not require ABO blood type matching, are provided in lower volumes (lower risk of adverse transfusion reactions) and are pathogen-reduced (lower risk of transfusion-transmitted infections). However, PCCs do not contain the full complement of procoagulants and anticoagulants that are present in FP and may carry a higher thrombotic risk.

A pilot study in bleeding patients undergoing cardiac surgery was conducted to compare PCC and FP in terms of safety and bleeding management effects and to assess the feasibility of a larger trial.