Hernandez: Complement activation in canine immune-mediated hemolytic anemia: A novel prognostic and therapeutic approach

Study Objectives

1) To determine the prognostic value of detecting complement activation in dogs with IMHA.

2) To evaluate the ability of two human complement inhibitors to inhibit dog complement proteins.

Executive summary

Immune-mediated hemolytic anemia (IMHA) is a common immune-mediated disease in the canine population, and up to 50% of dogs with this disease die within 2 weeks of presentation. In IMHA, the immune system attacks the dog’s own red blood cells (RBC) for unknown reasons. Destruction of the RBC leads to a lack of oxygen supply to the tissues, and results in organ injury. The initiating step in the disease process is the coating of RBC with auto-antibodies, which causes them to be removed from circulation by the spleen, or broken up within the blood stream by a group of proteins called complement. Activated complement proteins essentially punch holes in the red cell membrane, causing it to rupture. Release of iron and other proteins from the RBC causes additional damaging inflammation. In specific forms of human hemolytic anemia, treatment with complement inhibitors has revolutionized therapy and saved lives. Ultimately, we hope to enable veterinarians to treat IMHA in dogs with complement inhibitors. In order to achieve that, we first need a means to determine which dogs with IMHA have excessive levels of complement activation, and to prove that the available inhibitors are effective against dog complement proteins.