ALBERT

Description: Abstract 3328 Joint bleeding is the most frequent serious manifestation of hemophilia and results in significant morbidity, cost and decrement in quality of life. Although prophylaxis has significantly reduced both the frequency of joint bleeding and the development of arthropathy, hemarthrosis continues to be a problem, especially in patients with inhibitors. Understanding the pathobiology of blood-induced joint disease and developing measures to counter this problem remain as central issues in the field. The use of animal models to interrogate the earliest molecular and biochemical steps in this process is useful since such information is not available from humans. As the degree of induced joint bleeding in factor VIII deficient mice is heterogeneous, it is crucial to preclinical and basic research to assess and/or control bleeding severity in each comparable experimental group. Previously, we have created a mouse model of phenotypic variability based on injecting mice with varying concentrations of rFVIII. A chromogenic assay was used to assess the plasma levels of FVIII activity following treatment. [Hemophilia (2011), 17,565] Here we report on an objective system of four independent but inter-related measurements to document this phenotypic variability in a mouse model of hemophilia A: Visual Bleeding Score (VBS), joint diameter, Gross Bleeding Score (GBS) and Histological Bleeding Score (HBS). In order to achieve similar severities of hemarthrosis, groups of F8−/− mice were injected with rFVIII at specified time points prior to induction of bleeding. Each day following injury, the knee joints were examined for the presence of blood and the VBS was assigned. Three days after injury all mice were sacrificed, knee diameters were measured, GBS was assigned and the joints collected for histological examination to determine the HBS. At all-time points the data show a statistically significant correlation between gross (GBS) and histological (HBS) changes (0.87–0.99, P