Research Units are designed to provide clear summaries of results and impacts of research conducted at Canadian Blood Services. Written by Canadian Blood Services researchers in collaboration with the knowledge mobilization team, these summaries will help in further disseminating research findings to facilitate informed decision-making.
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.
Blood transfusion is a life-saving treatment used across all disciplines of medicine. In hospital blood banks, the red blood cell (RBC) supply chain faces challenges due to highly variable ordering decisions and over-frequent urgent orders. Hospitals tend to cope with this variability by holding excess inventory, which increases risk of wastage. This also prevents Canadian Blood Services, the manufacturer of blood components, from understanding the real need for RBCs.
Although there have been several initiatives aimed at reducing blood wastage, current hospital inventory management practice cannot adaptively respond to highly variable changes in demand and supply. For example, in Ontario over the last three years there were over 5,000 units of outdated red blood cells. This study proposes more accurate and efficient ways to manage blood demand and supply by improving demand forecasting and inventory management methods for RBCs.
Patients with immune thrombocytopenia (ITP) have low platelet counts and this can put them at risk for bleeding. There are treatments available to increase the platelet count in patients with ITP and this can be crucial in situations associated with blood loss, such as invasive surgeries. Intravenous immunoglobulin (IVIG) is commonly used to increase the platelet count before surgery for ITP patients, although available treatment options also include corticosteroids and eltrombopag, an oral medication that stimulates production of platelets. However, in addition to the many considerations that influence treatment preference, it is unclear if eltrombopag is non-inferior to IVIG as a perioperative treatment.
IVIG is made of concentrated proteins, specifically antibodies, that have been collected from plasma. However, IVIG is an expensive blood product in short supply and it can have side effects such as allergic reactions, headaches, and hemolysis. Corticosteroids may be avoided prior to surgeries as it can affect wound healing. Eltrombopag carries potential risks such as thrombosis and liver toxicity.
This study compared eltrombopag and IVIG for patients with ITP around the time of surgery. This is the only randomized control trial to date that has examined perioperative treatments for patients with ITP.
Blood donations, especially when repeated, can deplete iron stores (iron deficiency) and lead to low hemoglobin levels (anemia). Iron deficiency is common in regular whole blood donors, with fatigue the most commonly reported symptom. For women of child-bearing age, iron deficiency is of particular concern because it may be associated with poor outcomes in mothers and babies.
The screening test for donor hemoglobin done before each donation ensures that donors with a hemoglobin level below the cut-off do not donate. Donors are also informed about the need for increased iron in their diet and, for frequent donors, the advisability of iron supplementation. However, repeat donors could unknowingly have iron deficiency since the predonation screening process checks the hemoglobin levels of potential donors but not their iron stores, and it’s possible to have adequate hemoglobin levels to donate while still being iron deficient.
To better understand the potential impact of repeated blood donation by women, this study examined if there is an association between blood donations in female donors of child-bearing age and a risk of poor outcomes in the mother or her baby.
In Canada, red blood cells for transfusion are stored in the refrigerator at 1-6°C for up to 42 days, after which they are discarded. During storage, the cells change as they metabolize and age. This leads to accumulated degradation of their function and safety, which is seen as the cells change shape from a smooth disc to spiky sphere then a smooth sphere. This red blood cell “storage lesion” can be analyzed by laboratory tests. For example, cell shape is usually measured by experts who prepare the cells, spread them on a slide, look at them using a microscope and categorize their shape according to standard definitions, which places each cell into one of six shape sub-classes or “buckets”. These data are used to give a “morphology index” (MI) for the red blood cells. Using this traditional method, the loss of quality of red blood cells during storage has been very well characterized by researchers. However, the method is complex, time- and labour-intensive, prone to subjective bias, and limited by small sample sizes. The researchers aimed to address these limitations and come up with better methods to assess cell quality using label-free imaging and deep convoluted neural network learning algorithms.
Red blood cell (RBC) transfusion is an important treatment for some patients with sickle cell disease (SCD), one of the most common blood disorders in the world. Transfusion can reduce morbidity and mortality in patients with SCD, but it comes with risks: if donor RBCs have antigens that are not found on the patient’s RBCs, the patient’s immune system attacks the donor’s foreign RBC antigens through a process called alloimmunization. Alloimmunization puts SCD patients at risk of a haemolytic transfusion reaction (HTR), life-threatening hyperhaemolysis (rapid destruction of red blood cells) and other adverse outcomes. To minimize these risks, SCD patients are antigen matched to donors whose blood is typed for key RBC antigens through serology-based phenotyping. However, serological phenotyping is not foolproof; even when patients receive antigen-matched blood, alloimmunization rates can still reach 15% due to weak and partial antigen expression—this happens when mutations in one of the genes that code for a blood group antigen creates a variant of an RBC antigen. This study assessed whether genotyping could identify antigens not detected through serologic matching alone. By identifying differences in RBC antigen prediction and retrospectively evaluating alloimmunization-related outcomes, this study could help ensure safer transfusions for SCD patients.
Hemophilia is a genetic disorder that prevents blood from clotting normally, leading to prolonged bleeding. The two major types of hemophilia are caused by a mutation in either the F8 (hemophilia A) or F9 (hemophilia B) gene, which causes a deficiency in clotting factors VIII and IX, respectively. The severity of the disease (ranging from mild to severe) depends on the mutation or deletion observed in the F8 and F9 genes. The main treatment for hemophilia is replacement therapy, which involves injecting a patient with the missing clotting factor. This treatment can be expensive or, in lower-income countries, not available. When replacement therapy is available, serious problems associated with hemophilia A or B can be prevented and the life expectancy of the individual should approximate that of the general population.
To better understand the global burden of hemophilia, it is essential to have accurate data on the number of males with hemophilia across countries. Men are almost exclusively affected as the genes for these proteins are located on the X chromosome of which men have only one copy. The aim of this study was to accurately estimate prevalence at birth of hemophilia and life expectancy by type (A or B) and severity. Global comparisons of expected and observed numbers of patients with hemophilia can provide insights into the efficiency of healthcare systems.
Stem cell transplants are used to treat more than 80 diseases and disorders, including blood cell cancers such as leukemia. Cord blood — the blood left in the umbilical cord after a baby is born — is a rich and important source of stem cells for transplantation. The national Canadian Blood Services’ Cord Blood Bank collects, processes and freezes cord blood units. These units are available to any patient worldwide who needs a stem cell transplant and finds a match in the bank.
Before a cord blood unit that matches a patient can be released for transplantation, it must be tested for quality. To do these tests, the Cord Blood Bank uses a segment of the unit. Segments are small portions of the main unit that can be thawed separately. The results of tests conducted on thawed segments are used to make decisions about whether the cord blood unit will be suitable for transplantation. The tests count the numbers of certain types of cells. The tests also measure cell viability — the percentage of cells that can grow and divide into healthy cells to replace a patient’s damaged cells. Regulations and standards provide criteria for the number and viability of certain cells in cord blood units that must be met for the unit to be considered suitable for transplantation.
In this study, the researchers set out to improve the pre-transplant quality tests of thawed cord blood. The aim was to develop a standard approach that minimizes cell loss while maintaining cell viability, thus increasing the chance that units meet the standards and are found suitable for transplantation.