Defining disease mechanisms in Immune Thrombocytopenia (ITP) and their association with clinical outcomes

Immune thrombocytopenia (ITP) is a disease of low blood platelets that affects 1 in 8,000 Canadians. People with ITP have a tendency to bleed and 1 in 100 will suffer a bleed in the brain (stroke) or die from bleeding or infection. ITP affects people differently: Some people bleed while other do not, and some treatments work in certain people but not in others. These differences are so pronounced that it has led scientists to think that ITP is not one disease, but rather a group of different diseases. If we can figure out what makes ITP different from one person to the next, we will be able to come up with better ways of treating it. ITP was believed to be caused by proteins in the blood called antibodies that attacked and destroyed platelets, leading to platelet destruction. But recent studies have shown that the platelet mother cell, the megakaryocyte, is also affected, leading to reduced platelet production. Our research aims to figure out why platelet production is reduced. To do this we will use a new test that we designed to study megakaryocytes in the laboratory, and clinical information from one of the largest patient registries Canada, which our group is leading. We will test blood from ITP patients for an array of possible antibodies that attach to, and injure megakaryocytes. Our laboratory experiments will confirm the types of antibodies, define their characteristics and demonstrate how they prevent megakaryocytes from making new platelets. We will link our discoveries in the laboratory directly with patient outcomes. By doing so, we will be able to identify patients who are more prone to bleeding, and the treatments that are most suitable for them.

ARNOLD, Donald

McMaster University

Canadian Blood Services-CIHR Partnership Operating Grant Program

Ontario

317469.0