Fibrin at the interface of platelet activation and thrombus stabilisation

Platelets are small cells in the blood which clump together and form a blood clot at sites of injury. However, excessive clotting in diseased blood vessels, such as at sites of fatty plaques, can lead to blockage and precipitate a heart attack or stroke. Patients at risk of life-threatening clots are treated with drugs, such as aspirin, that block platelet activation. However, all current drugs carry a risk of bleeding which in some cases can be life threatening. We have made a discovery that rewrites our understanding of blood clotting. We have shown that fibrin which is known to form a mesh-like structure that supports the blood clot also drives platelet clumping. Thus fibrin not only strengthens the blood clot but it also causes it to grow.

We propose that drugs that block this action of fibrin represent new forms of treatment for patients at risk of thrombosis. We will study the molecular mechanisms underpinning this interaction and generate inhibitors including proteins that will allow this hypothesis to be tested in human blood and in mice.