Grant: Operating Grant

Platelets are small blood cells responsible for forming clots at the site of bleeding. They aggregate to form a cellular plug, strengthen the coagulation system when blood vessels are injured, and are critical in preventing blood loss. Immune thrombocytopenia (ITP) is a disease where the immune system mistakenly produces antibodies which destroy the patient's own platelets. Thus, the patient cannot stop bleeding properly, which can lead to severe health problems or death. The antibodies in this disease attack two proteins (antigens), called GPIIbIIIa and GPIb, which are on the surface of platelets. These proteins are responsible for physically connecting platelets together and sticking to the vessel wall to stop bleeding. Approximately 70-80% ITP patients have antibodies to GPIIbIIIa, 20-40% patients have antibodies to GPIb, and some patients have antibodies to both proteins. Currently, it is not clear whether the antibodies to GPIIbIIIa and GPIb work the same (mechanism of disease), and if ITP caused by antibodies to these two proteins can be treated successfully by the same therapies. We also do not know whether some patients have more severe bleeding than others because of the specific type of antibodies in their blood (i.e. whether severity is related to the protein or the sub-section of the protein that the antibody attacks). We propose to address these questions and investigate whether antibodies against GPIb and GPIIbIIIa may act differently by causing: i) a change in platelet signalling activity, or ii) changing the physical structure of GPIIbIIIa and GPIb proteins, or iii) affecting platelet generation. We think that different antibodies may affect platelet function in a different manner, determine where platelets are destroyed, and how patients respond to current clinical therapies (e.g. removing patient's spleen or treatment with IVIG).