Activation of the contact pathway of coagulation in cardiovascular diseases

Our blood clotting system protects us from bleeding, and is crucial for survival. On the other hand, undesired activation of blood clotting is the most important cause of death. Indeed, when blood clots form inside the blood vessels, it can cause heart infarcts, stroke, or obstruction of the lung blood vessels.Luckily, we have effective drugs that prevent blood clotting. These drugs are used to prevent deaths and disability in millions of patients. However, by reducing blood clotting, these drugs increase the risk of bleeding. Major, sometimes fatal, bleeding is a major side-effect of those drugs, and an important limitation to their use.There is increasing evidence that a specific part of the blood clotting system, the 'contact activation system', is important for undesired activation of blood clotting but is not required for protection against bleeding. Promising animal studies confirm that experimental drugs that target contact activation can effectively prevent blood clots inside blood vessels, without interfering with normal blood clotting that stops bleeding. These drugs have the potential to provide safer treatment for millions of patients. However, crucial information is still lacking.Importantly, while the animal studies are promising, there is insufficient data on this contact activation system in human disease.In this project, we will describe in detail how contact activation contributes to different diseases. This will help the development of safer drugs.

Keywords:stollingsaciviteit

Disciplines:Cardiac and vascular medicine