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.
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.
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.
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.
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.