Autoimmune disease develops in dogs when their immune system "goes rogue" and destroys normal healthy cells in the body. Immune thrombocytopenia (ITP) is a serious bleeding disorder that results from immune destruction of platelets, small blood cells that play a critical role in preventing bruising and bleeding after injury. Old English Sheepdogs and Cocker Spaniels appear to have a special susceptibility to ITP, however ITP afflicts all dogs regardless of breed. Dogs with ITP develop bruises and pinpoint hemorrhage in the skin. In the most severe cases, dogs bleed from the intestinal and urinary tracts, and may die from blood loss. Fortunately, most dogs survive ITP, but they may relapse months to years after their first episode. The treatment of ITP involves protracted courses of potent, non-specific immunosuppressive drugs that impact quality of life. Common drug side effects include urinary incontinence, hair loss, and intestinal ulcers. Bone marrow suppression and sepsis are potentially fatal treatment complications. Pet owners face emotional and financial challenges from the time of their dog's initial ITP diagnosis through prolonged follow-up periods. Our study will use a genetic approach to understand what causes the immune system to go awry in ITP. We will also look for laboratory markers that predict bleeding severity so that veterinarians can reserve aggressive treatment for only those dogs at risk of significant blood loss. The results of this research will improve ITP diagnosis and predictions of relapse, and lead to better, targeted therapies that minimize treatment side effects.