Figure 5.
Inhibition of leukocyte adhesion to P-selectin substrate under vascular mimetic flow. Leukocytes isolated from the venous blood of patients with SCD (n = 10). Cell suspension with or without addition of crizanlizumab or inclacumab (at different concentrations) perfused through microfluidic flow channels coated with recombinant human P-selectin. FA-WBC-Psel was estimated as described in Methods. Relative fold change in FA-WBC-Psel from baseline was calculated from the mean (±SD) at each concentration tested among all 10 patients. Baseline adhesion (shown in box) defined as baseline leukocyte adhesion to P-selectin substrate across the 10 patients. Shear stress of 1 dyne/cm2 with a pulsatility of 1.67 Hz. In relation to the clinically approved crizanlizumab dose (5.0 mg/kg), a concentration of 100 μg/mL corresponds to Cmax (maximum plasma concentration) and ∼10 to 15 μg/mL corresponds to Ctrough (trough plasma concentration).

Inhibition of leukocyte adhesion to P-selectin substrate under vascular mimetic flow. Leukocytes isolated from the venous blood of patients with SCD (n = 10). Cell suspension with or without addition of crizanlizumab or inclacumab (at different concentrations) perfused through microfluidic flow channels coated with recombinant human P-selectin. FA-WBC-Psel was estimated as described in Methods. Relative fold change in FA-WBC-Psel from baseline was calculated from the mean (±SD) at each concentration tested among all 10 patients. Baseline adhesion (shown in box) defined as baseline leukocyte adhesion to P-selectin substrate across the 10 patients. Shear stress of 1 dyne/cm2 with a pulsatility of 1.67 Hz. In relation to the clinically approved crizanlizumab dose (5.0 mg/kg), a concentration of 100 μg/mL corresponds to Cmax (maximum plasma concentration) and ∼10 to 15 μg/mL corresponds to Ctrough (trough plasma concentration).

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