ARFI-Monitored Hemostatic Challenge for Assessment of In Vivo Hemostasis in Canine Models of Inherited Bleeding Disorders

The need for a validated in vivo assay to test the efficacy and safety of therapeutic agents for hemostatic disorders is paramount as new clotting factor replacement therapies are developed. Current hemostatic assays are almost exclusively ex vivo. Conventional in vivo assays are limited in application to relevant animal models, and suffer from a lack of reproducibility. This thesis demonstrates that Acoustic Radiation Force Impulse - Monitored Hemostatic Challenge (ARFI-MHC) may be an alternative in vivo assay for the measurement of hemostatic metrics. Time to hemostasis (TTH) and rate of hemorrhage (RH) were measured in dogs for six hemostatic phenotypes. Two algorithms were compared for TTH and RH measurements with spatial clustering for noise reduction. Each method was evaluated for reproducibility and validated using autologous blood infusions. ARFI-MHC was capable of distinguishing bleeding phenotypes based on TTH and RH measurements, and demonstrated better reproducibility versus conventional in vivo assays.Master of Scienc