Assessment of Hypercoagulability in Canine Pituitary-Dependent Hyperadrenocorticism
Dogs with pituitary-dependent hyperadrenocorticism (PDH) are at increased risk of thromboembolic disease (TED); however the pathogenesis of thrombosis in these patients is poorly characterized. Thromboelastography (TEG®) is a whole blood hemostatic test that has recently been shown to be capable of detecting hypercoagulability in veterinary patients. A modification of TEG, PlateletMappingTM (TEG-PM) measures platelet response to the agonists arachidonic acid (MAAA) and adenosine diphosphate (MAADP), and compares this to fibrin clot strength in the absence of platelet activation (MAfibrin). This prospective study evaluated dogs with PDH for hypercoagulability using TEG-PM as well as conventional plasma-based coagulation tests (prothrombin time [PT], activated partial thromboplastin time [aPTT], fibrinogen concentration). Hemostatic testing was performed in 40 healthy dogs, 19 dogs with untreated PDH, 16 of the dogs with PDH after 3 months’ treatment and 15 dogs after 6 months’ treatment. Systolic blood pressure (SBP) was also measured in all the dogs with PDH before and during treatment. In addition, urine protein to creatinine ratio (UPCR) and antithrombin activity [AT] were measured in some dogs with PDH. PT was significantly decreased in the dogs with PDH compared to controls, however all of the dogs with PDH had results within the reference interval. Dogs with PDH were hyperfibrinogenemic compared to healthy dogs; fibrinogen concentrations reduced with treatment of PDH but remained significantly elevated. AT activity in the PDH dogs was not significantly decreased despite the majority of dogs tested having significant proteinuria. Approximately half of the dogs with untreated PDH were hypertensive, and blood pressure did not change significantly following resolution of hypercortisolemia. Serum cholesterol was increased in dogs with untreated PDH but normalized following control of PDH. TEG-PM revealed decreased κ, increased α-angle and increased MAthrombin in dogs with PDH in comparison to healthy dogs. Platelet response to AA was significantly increased in dogs with untreated PDH. Following treatment of PDH, the majority of TEG-PM parameters (with the exception of MAthrombin) did not change significantly. In conclusion, dogs with PDH had evidence of hypercoagulability and hypertension, which persisted despite medical treatment of PDH. These factors may explain the association between hyperadrenocorticism and TED.