Investigating alternatives to standard anticoagulant drugs

An investigation of Factor XI and proteins from the contact system (renewal)

Anticoagulants are given to people to prevent deep vein thrombosis (a blood clot in a vein) or pulmonary embolism (a blood clot on the lungs) in people having surgery, or to prevent stroke in people with an abnormal heart rhythm, called atrial fibrillation (AF). The dose of anticoagulant drug a person receives is crucial - if too little drug is given it will not prevent further blood clots, but if too much is given it can lead to excess bleeding, which can be fatal. All current anticoagulant drugs, such as warfarin and even newer drugs, carry a risk of excess bleeding, and therefore must be closely monitored. So although anticoagulant drugs reduce the chances of people with AF experiencing a stroke, only a fraction of people in the UK with AF actually take them because of the high risk. Professor Jonas Emsley at the University of Nottingham is studying proteins called factor XI (FXI) and kininogen, which circulate in the blood and are key components in blood clot development. People with reduced levels of these proteins are less likely to develop blood clots and rarely have life-threatening bleeds. Blocking the activity of these proteins using drugs may therefore be a good way to treat thrombosis. The BHF have awarded a grant to Professor Emsley to study these molecules further. FXI and kininogen are bound tightly together in a complex, so Professor Emsley will find out the molecular structure or bound shape and work out how they interact with each other. He will also study people with an inherited deficiency in the FXI protein, which may reveal more about thrombosis and new ways to prevent blood clotting without risk of fatal bleeding.