The Factor XIIa and VWF partnership: a potential drug target to prevent thrombosis?

Mapping the interaction of VWF with FXIIa and its potential as a new anti-coagulant target

Dr Thomas McKinnon and his colleagues at Imperial College London are studying the processes underlying blood clotting to look for ways to prevent unwanted blood clotting, or thrombosis, without causing bleeding. Von Willebrand Factor (VWF) & Factor XII (FXII) are two proteins that perform separate functions in blood clotting. VWF captures platelets, keeping them close to damaged blood vessels where they form the blood clot, whereas active FXII (FXIIa) helps to form a protein called fibrin that stabilises the blood clot. Dr McKinnon recently discovered that FXIIa attaches to VWF and boosts the number of platelets that VWF can capture, particularly at places where blood flows fast in narrowed blood vessels, VWF can also capture FXIIa, which ultimately leads to more blood clotting. Preventing FXIIa attaching to VWF may be a way to reduce the amount of platelets VWF can capture and to prevent unwanted thrombosis. In this project, Dr McKinnon will establish how VWF and FXIIa interact with each other and what effect this has on blood clotting. Blocking FXII function has been shown to reduce the risk of thrombosis and, importantly, low levels of FXII do not lead to excessive bleeding. This makes FXII a potentially safe target for anticlotting drugs. Dr McKinnon’s research may therefore reveal a new way to block excessive unwanted blood clotting using drugs, without excessive bleeding.