Research of the interaction between VWF and 'neutrophil extracellular traps' in trombotic microangiopathies.

White blood cells are essential for fighting infection using specific killing mechanisms. However, when these processes get activated in the absence of infection, this can cause disease. Similarly, von Willebrand factor (VWF), which serves as a sort of glue during blood clotting by sticking platelets (small blood cells) to damaged blood vessels, can also lead to disease when it gets released without injury. One of the ways that white blood cells try to fight infection is by sending out neutrophil extracellular traps (NETs), or ejecting their DNA lined with proteins that can kill bacteria. These same proteins also damage healthy blood vessels and cause them to release more VWF, which binds platelets and can lead to small blood clots. Activated platelets are one way that white blood cells can be stimulated to make NETs, and therefore this is a vicious cycle. We aim to better understand how VWF and platelets can trigger this release of NETs from white blood cells and to see if this occurs in diseases where small blood clots form in important organs leading to organ failure and sometimes death. By inhibiting these interactions in mouse experimental models, we hope to see a protective effect in disease states. We will also look at patients with these diseases and see if these NETs are involved in regulating the severity of the disease in different people. We hope to gain insight into new treatments for these deadly diseases where small blood clots lead to organ failure.