How dying platelets help clots to form

HMGB1, a novel pro-thrombotic signal released by necrotic platelets

Dr Matthew Harper and his team at the University of Cambridge are studying how platelets release a molecule called HMGB1, which promotes blood clotting. Platelets are small blood cells that clump together to form clots and prevent excessive bleeding after injury. But platelets can also form clots in diseased arteries (thrombosis), and if these clots block the artery they can lead to a heart attack or stroke. When a platelet is activated to form a clot it releases molecules that activate nearby platelets, which then clump together to form a ‘plug’. But we don’t fully understand how this happens. The HMGB1 molecule, which Dr Harper is studying, is released by platelets that seem to be dying and whose outer surface is disintegrating. This is an unusual way for platelets to release pro-clotting factors and has attracted Dr Harper’s interest. Dr Harper also believes the effect HMGB1 has on the neighbouring platelet depends on how it attaches to the platelet. In this project, he will work out exactly how platelets release HMGB1 to activate other platelets, and how this promotes clotting. Understanding HGMB1’s role in platelet activation could reveal a new way to block the protein’s clotting actions and reduce the risk of blood clots in people with heart disease.