Figure 2.

Effects of plasma kallikrein knockdown in rat models of arteriovenous (AV) shunt thrombosis and cuticle bleeding. AV shunt study and cuticle bleeding study were carried out on the rats at day 7 postdosing in the study described in Figure 1. Ex vivo measurements in plasma were also pursued. All results are expressed as mean and standard error of mean. (a) Circulating levels of plasma kallikrein zymogen (plasma prekallikrein) in the various treatment groups at day 7 were determined by the plasma kallikrein enzyme assay as described in Methods. Percent change compared to nt control is noted on the graph. (b) Ex vivo activated partial thromboplastin time (aPTT) at day 7. Percent increase compared to nt control is noted on the graph. (c) Ex vivo prothrombin time (PT) at day 7. Percent increase in the Klkb1:(287) 0.5 mg/kg treatment group compared to nt control is noted on the graph. (d) Percent inhibition of clot weight relative to nt control. Apixaban (3 mg/kg, n = 6 per group) was included as a benchmark. (e) Percent increase in bleeding time relative to nt control. Apixaban (3 mg/kg, n = 6 per group) was included as a benchmark. *P < 0.05, **P < 0.01, ***P < 0.001 compared to nt control for Klkb1:(287) or compared to vehicle control for apixaban.