Pryzdial, Ed

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.