Canadian Blood Services
Centre for Blood Research – University of British Columbia
Pathology and Laboratory Medicine – University of British Columbia
- Doctor of Philosophy in Biochemistry, University of Toronto
- Bachelor of Science in Biology, Chemistry and Biochemistry, University of Toronto
University of British Columbia
Centre for Blood Research
2350 Health Sciences Mall
Vancouver, BC, Canada V6T 1Z3
Clotting, Clot-busting and Bleeding - Finding the Right Balance
Dr. Pryzdial’s research group investigates the regulation of clot formation (coagulation), including the effects of viruses and how clots dissolve (fibrinolysis); the molecular basis of clotting protein deficiency in patients; and the quality of clotting constituents in blood products.
Why is this important?
Understanding the complicated processes by which clotting proteins are controlled has led to a novel treatment to “bust clots” with anticipated impact on blood product utilization for cardiac surgery. In patients that bleed, discovery of inherited modes of compensation that curtail their blood-loss may also be utilized to conserve blood products. Expertise in clotting protein biochemistry helps maintain an extremely high standard for the Canadian Blood Services plasma quality assurance program.
Dr. Pryzdial studies “non-traditional” functions of blood clotting proteins and their novel application. Combining biochemistry and molecular engineering, Dr. Pryzdial’s group has discovered new functions for several clotting proteins with possible therapeutic or diagnostic applications to heart disease and stroke. In particular, they are focusing on a previously unknown mechanism of communication between the clotting protein factor Xa and the clot-dissolving pathway. They have shown that, after enzymatic modulation, factor Xa becomes an accelerator of the fibrinolysis enzyme called tissue plasminogen activator which is now an important life-saving therapeutic. However, tissue plasminogen activator is beneficial in less than 10% of possible cases and Dr. Pryzdial’s research has led to the development of derivatives of factor Xa that may improve patient outcome.
As part of a team effort within the Centre for Blood Research (University of British Columbia), Dr. Pryzdial’s lab determines the genetic basis of patients with rare clotting deficiencies. The responsible protein is cloned and expressed containing the identified mutation. In this way, nature provides clues to explain how protein structure impacts protein function, and also helps to understand other differences these exceedingly rare individuals (1:2,000,000) may have been born with to compensate for an otherwise lethal deficiency. These compensatory mechanisms alleviate blood-loss and their delineation will reduce the use of transfusion products not only for these patients, but with anticipated general applicability.
Dr. Pryzdial is also a member of the Canadian Blood Services plasma quality assurance team (led at Canadian Blood Services, McMaster University) and has particular interest in the efficacy of coagulation-related proteins on transfusion outcome.
- Hun Yeon J, Chan KY, Wong TC, Chan K, Sutherland MR, Ismagilov RF, Pryzdial ELG, Kastrup CJ. A biochemical network can control formation of a synthetic material by sensing numerous specific stimuli. Sci Rep 2015; 5:10274.
- Talbot K, Meixner SC, Pryzdial ELG: Proteolytic modulation of factor Xa–antithrombin complex enhances fibrinolysis in plasma. BBA-Proteins Proteom 2013; 1834:989-995.
- Sheffield WP, Bhakta V, Talbot K, Pryzdial ELG, Jenkins C: Quality of frozen transfusable plasma prepared from whole blood donations in Canada: An update. Transfus Apher Sci 2013; 49:440-446.
- Vanden Hoek AL, Talbot K, Carter ISR, Vickars L, Carter CJ, Jackson SC, MacGillivray RTA, Pryzdial ELG: Coagulation Factor X Arg386 specifically affects activation by the intrinsic pathway: A novel patient mutation. J Thromb Haemost 2012; 10:2613-2615.
Blood Clotting Constituents and Viruses - Novel Interplay
Members of Dr. Pryzdial’s laboratory investigate how blood clotting proteins enhance infection by viruses; and the persistence of viruses in blood products.
Why is this important?
This research has revealed that clotting constituents are exploited by viruses. Furthermore, platelets and red cell units have been shown to harbour and, surprisingly, replicate a prevalent transfusion-transmissible virus. This combined knowledge may further improve the safety of blood products.
Uniquely combining mutated viruses propagated in host cells with restricted protein expression has enabled Dr. Pryzdial’s group to find that model enveloped viruses from the Herpes family can directly assemble clotting enzyme-cofactor-substrate complexes on their surfaces to generate clots. This bypasses the normal strict inhibition of coagulation enzyme activation imposed by cells except at sites of vascular damage. Virus-initiated clot formation can not only contribute to heart disease, but enhances the susceptibility of infection through cell signaling via protease activated receptors. This model virus work provides general insight into many viruses that have a similar envelope structure and the comparable host cell-derived proteins that are incorporated; as possible examples, West Nile, Hepatitis B and C, Human Immunodeficiency and Dengue viruses.
Dengue virus, a highly transfusion-relevant member of the Flavivirus family, was shown to be bound and replicated by platelets. Platelets are enucleated cells that are essential to clotting. Platelets are a vital transfusion blood product to control bleeding. Therefore this observation has implications during the storage of platelet units for transfusion. As global Dengue virus infection is estimated to approach 400 million annually, with platelet loss as a hallmark, this finding also helps to understand pathology.
- Sutherland MR, Simon AY, Serrano K, Schubert P, Acker JP, Pryzdial ELG: Dengue virus persists and replicates during storage of platelets and red blood cell units. Transfusion 2016:doi10.1111/trf.13454.
- Simon AY, Sutherland MR, Pryzdial ELG: Dengue virus binding and replication by platelets. Blood 2015; 126:378-85.
- Pryzdial ELG, Sutherland MR, Ruf W: The procoagulant envelope virus surface: contribution to enhanced infection. Thromb Res 2014; 133:S15-17.
- Sutherland MR, Simon AY, Serrano K, Schubert P, Acker J, Pryzdial ELG: Dengue virus persists in stored platelets and red blood cells. Transfus Med Rev 2014; 28:167.
- Sutherland MR, Ruf W, Pryzdial ELG: Tissue factor and glycoprotein C on herpes simplex virus type 1 are protease-activated receptor 2 cofactors that enhance infection. Blood 2012; 119:3638-3645.
Click to see Leadership Roles:
|Current||Associate Director, Centre for Blood Research|
|2014 - Current||Chair, Scientific Review Sub-Committee, Heart and Stroke Foundation of Canada|
|2014 - Current||Associate Director, Exams, Graduate Studies Program, UBC, Pathology and Laboratory Medicine|
|2011 - Current||Member, Editorial Advisory Panel, Biochemical Journal|
For general enquiries about research at Canadian Blood Services, please contact us at:
Centre for Innovation
Canadian Blood Services
1800 Alta Vista Drive
Ottawa, Ontario K1G 4J5