Fibrin at the interface of platelet activation and thrombus stabilisation

Blood clots can grow dangerously large because a protein called fibrin, which forms the mesh that holds clots together, also activates more platelets—the cells that create the clot in the first place. This discovery upends a long-held assumption. For decades, scientists thought the platelet receptor GPVI only responded to collagen, which triggers clot formation when a blood vessel is injured. The team behind this grant has shown that GPVI also responds to fibrin, meaning it drives both the start and the spread of a clot. This explains why mice lacking GPVI have unstable clots that break apart and travel through the bloodstream—a process called embolisation that can cause strokes or heart attacks. If the researchers succeed in mapping exactly how fibrin binds to GPVI, and then develop inhibitors that block that specific interaction without interfering with GPVI’s response to collagen, they could create a new class of antiplatelet drug. Current drugs like aspirin or clopidogrel reduce clotting but also increase bleeding risk. A drug that targets only the fibrin-GPVI interaction might stabilise clots without the same bleeding side effects. This is fundamental science with a clear translational goal. The work will also clarify GPVI’s role in maintaining blood vessel integrity, which could affect how we understand conditions beyond thrombosis.