A novel clot-dissolving agent derived from clotting factor Va

Clots that obstruct the flow of blood are a leading cause of death worldwide. The prevailing treatment to dissolve these clots is a blood constituent, called tissue plasminogen activator (tPA). tPA has saved many lives but needs improving because of the life-threatening risk for bleeding due to the required high dosage compared to normal levels. Numerous attempts have been made to improve the safety and effectiveness of tPA, but these have failed in clinical trials. The lack of success demonstrates a knowledge gap in how tPA works. The current project fills this gap by our recent discovery that additional blood proteins play a role in dissolving clots. We have shown that the protein blood clotting factor V (FV) has a function other than sealing leaks in blood vessels. FV can be broken down into a fragment that reverses functions to speed up clot-dissolving by helping tPA. Excitingly, the data show that combining fragmented FV together with tPA dissolves clots much better than tPA alone. Therefore, lower doses of tPA can be given to patients, causing a reduction in its harmful side effects. This highlights a new therapeutic application for a constituent of blood with promise to save lives.

PRYZDIAL, Ed

University of British Columbia

Graduate Fellowship Program

British Columbia

$39,500