Rivaroxaban and Apixaban Induce Clotting Factor Xa Fibrinolytic Activity
This week we profile a recent publication in the Journal of Thrombosis and Haemostasis from
Dr. Rolinda Carter (pictured) and Dr. Ed Pryzdial at the UBC Life Sciences Institute.
Can you provide a brief overview of your research focus while you were in Ed’s lab?
In previous years, the Canadian Blood Services’ Pryzdial lab at the UBC Centre for Blood Research identified a new role for clotting factor Xa (FXa) in a completely opposite activity, clot dissolution (i.e. fibrinolysis). This function is acquired through specific cleavages that turn FXa into an accelerator of plasmin, the physiological scissors tasked with cutting and removing clots. It is plasmin that cleaves FXa, first producing a fragment called FXaβ and then a second fragment called Xa33/13. In plasma, the “clot-busting” function of FXa is rapidly inactivated but can be maintained by chemically blocking its enzymatic site such that FXaβ is not subsequently cleaved to generate Xa33/13. In more recent years, rivaroxaban (Xarelto) and apixaban (Eliquis), FXa-directed oral anticoagulants (DOACs), were approved to prevent clot formation. Since they block the enzymatic site of FXa, Dr. Carter’s research tested the ability of these DOACs to enhance the degradation of clots by modulating FXa function.
What is the significance of the findings in your publication?
The research identified a new role for rivaroxaban and apixaban in dissolving clots. The use of these DOACs resulted in the generation and stability of FXaβ, and thus in faster plasmin production and fibrinolysis. Plasma clots from rivaroxaban-treated patients broke-down faster than clots in normal plasma. More FXaβ in plasma was directly correlated with faster “clot-busting”. These findings may suggest an added benefit in using these DOACs to treat deep vein thrombosis and thus prevent post-thrombotic syndrome, a condition with links to ineffective clot degradation.
What are the next steps for this research?
On-going research is focusing on obtaining pre-clinical data in animal models of thrombosis to evaluate the therapeutic application of DOACs as clot-dissolving medicines and in mitigating post-thrombotic syndrome. Additional studies are also underway for the optimization of therapeutics that emulates this new-found effect of DOACs.
This research was funded by:
This research was funded by the Heart and Stroke Foundation of Canada and by a graduate scholarship from the University of British Columba.
Dr. Rolinda Carter has recently taken up the post as Dean of Academics at the University of St Martin in the Caribbean. Among other tasks, Dr. Carter is mandated with increasing science course offerings at the University.