Figure 1.
Blood loss volume in a mouse tail clip model is reduced by SerpinPC treatment in a dose- and time-dependent manner. (A) Blood loss volume over a 20-minute observation period is plotted for background strain B6;129S mice (magenta), and fVIII-deficient (HA) mice treated with vehicle (red), human fVIII at doses of 100 and 400 U/kg (green), or SerpinPC at 0.3, 1, 10, and 100 mg/kg (blue). Tails were transected 15 minutes after the injection of vehicle, fVIII, or SerpinPC. Blood loss values for vehicle-treated mice are taken from multiple experiments, and those for HA mice treated with 100 U/kg are taken from 2 separate experiments. For all other conditions, 3 mice were used per group, with median indicated by a line. (B) The effect of time of pre-exposure to SerpinPC on blood loss volume was assessed at a dose of 0.3 mg/kg. SerpinPC was injected 15, 60, and 120 minutes before tail transection, and blood loss was measured over a 20-minute period similar to that in panel A. Vehicle-treated HA and background control blood loss levels are indicated by a dashed line, with a gray area representing 1 standard deviation, calculated from panel A. Three mice were used per group, with average and standard deviation plotted. The line represents a nonlinear fit, forced through the average untreated value at t = 0. (C) To determine the lowest single dose of SerpinPC capable of reducing blood loss volume in the HA mouse, doses of 0.01, 0.03, 0.1, 0.3, 1, 3, and 10 mg/kg were given 12 hours before tail transection. The average blood loss volume of untreated HA and control mice are indicated similar to that in panel B. Dose dependency of blood loss is nonlinear, plateauing in the WT blood loss range at a dose of ∼1 mg/kg SerpinPC. Three mice were used per group with average and standard deviation plotted.

Blood loss volume in a mouse tail clip model is reduced by SerpinPC treatment in a dose- and time-dependent manner. (A) Blood loss volume over a 20-minute observation period is plotted for background strain B6;129S mice (magenta), and fVIII-deficient (HA) mice treated with vehicle (red), human fVIII at doses of 100 and 400 U/kg (green), or SerpinPC at 0.3, 1, 10, and 100 mg/kg (blue). Tails were transected 15 minutes after the injection of vehicle, fVIII, or SerpinPC. Blood loss values for vehicle-treated mice are taken from multiple experiments, and those for HA mice treated with 100 U/kg are taken from 2 separate experiments. For all other conditions, 3 mice were used per group, with median indicated by a line. (B) The effect of time of pre-exposure to SerpinPC on blood loss volume was assessed at a dose of 0.3 mg/kg. SerpinPC was injected 15, 60, and 120 minutes before tail transection, and blood loss was measured over a 20-minute period similar to that in panel A. Vehicle-treated HA and background control blood loss levels are indicated by a dashed line, with a gray area representing 1 standard deviation, calculated from panel A. Three mice were used per group, with average and standard deviation plotted. The line represents a nonlinear fit, forced through the average untreated value at t = 0. (C) To determine the lowest single dose of SerpinPC capable of reducing blood loss volume in the HA mouse, doses of 0.01, 0.03, 0.1, 0.3, 1, 3, and 10 mg/kg were given 12 hours before tail transection. The average blood loss volume of untreated HA and control mice are indicated similar to that in panel B. Dose dependency of blood loss is nonlinear, plateauing in the WT blood loss range at a dose of ∼1 mg/kg SerpinPC. Three mice were used per group with average and standard deviation plotted.

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