Investigating the cause of blood clotting in dogs with IMHA
Immune-mediated hemolytic anemia (IMHA) is a common, and often life-threatening, blood disorder in dogs. In this condition, the dog’s immune system attacks its own red blood cells, leading to a severe anemia that is treated with immunosuppressive drugs. However, affected dogs suffer from more than just anemia. They also have over-active clotting systems that lead to abnormal blood clot formation. These blood clots can be fatal if they block off the blood supply and delivery of nutrients and oxygen to vital tissues, causing serious organ damage and failure. We now treat dogs with blood thinners to try and prevent these clots from forming, but dogs with IMHA continue to suffer from lethal blood clots, indicating that we need to identify more effective therapy.
When clots form in the body, they are gradually broken down by enzymes – this normal process is called fibrinolysis. If clots are not broken down properly, they will persist in the blood vessels, causing tissue damage. We suspect that clot breakdown is defective in dogs with IMHA, leading to persistence of blood clots. We believe the decreased fibrinolysis is caused by too much of a blood protein, called PAI-1. PAI-1 protein is the main inhibitor of clot breakdown and if it is too high, clots remain in blood vessels and prevent normal blood flow. Our theory that high PAI-1 levels prevent normal clot breakdown is based on recently published data on dogs with IMHA. These dogs had high levels of the PAI-1 precursor (mRNA) in the circulation – in fact, the mRNA was up to 17-times higher than in healthy dogs. Our preliminary studies have also shown decreased clot breakdown in blood samples from dogs with IMHA.
In this proposal, we plan to determine whether dogs with IMHA have high levels of active PAI-1 protein (not just mRNA levels) as a major cause of reduced clot breakdown. In this project, we will collect blood samples from 40 dogs with IMHA and 40 healthy control dogs and measure PAI-1 protein activity levels and mRNA levels, and perform laboratory tests of clot breakdown. We will also test whether a drug that blocks PAI-1 activity can improve fibrinolysis in these test samples. Importantly, the blood thinning drugs currently given to dogs with IMHA to prevent clot formation do not affect clot breakdown at all. If we find that high PAI-1 levels result in reduced clot breakdown in dogs with IMHA, then PAI-1 inhibitor drugs will open up new possibilities for more effective treatment. Our goal is to improve on current IMHA treatment so that abnormal blood clot formation no longer limits dogs’ survival.
Eligibility: Only dogs who have not been treated for IMHA with immunosuppressive drugs (such as prednisone or other steroids) or anticoagulants (such as aspirin or heparin) before enrollment are eligible.
Compensation: There will be no charge for the additional tests run on your pet.
Owner Responsibilities: You will be asked to allow us to collect a small amount of additional blood on your dog. There are no further obligations or responsibilities.
Principal Investigator: Tracy Stokol, BVSc, DACVP
Sponsor: This research is funded by the AKC Canine Health Foundation (link is to an external site)
Contact/Schedule an Appointment: Please contact the internal medicine service, the emergency service, or the clinical trials coordinator at 607.253.3060, or email firstname.lastname@example.org. Your referring veterinarian may also contact the hospital to refer your pet.
Other Participating Institutions: Cornell University Veterinary Specialists in Stamford, CT, Rochester Specialist and Emergency Services, Auburn University, and University of Minnesota.