![Vox, PKR activator, and GBT021601 reduce microcapillary occlusion in HbSS RBCs under normoxia and hypoxia. (A) OcclusionChip device used to assess RBC-mediated microcapillary occlusion under normoxic (pO2 ≈ 100 mm Hg) and mixed venous hypoxic (pO2 ≈ 44 mm Hg) conditions. (B) Microcapillary OI comparison between sickle (HbSS) and healthy (HbAA) RBCs under normoxia (HbAA [n = 8] vs HbSS [n = 15]; ∗∗∗P < .001) and hypoxia (HbAA [n = 8] vs HbSS [n = 15]; ∗∗∗P < .001, Mann-Whitney U test). (C) Under normoxia, treatment with Vox, PKR activator, or GBT021601 significantly reduced OI in HbSS RBCs (HbSS vs HbSS + Vox; HbSS vs HbSS + PKR; HbSS vs HbSS + GBT021601; n = 7; ∗P < .05; Wilcoxon test). (D) Similar reductions were observed under hypoxia (HbSS vs HbSS + Vox, n = 12 [∗∗∗P < .001]; HbSS vs HbSS + PKR, n = 12 [∗∗∗P < .001]; HbSS vs HbSS + GBT021601, n = 6 [∗∗∗P < .001]; Wilcoxon test). (E) Summary of mean ± SEM OI for HbAA, HbSS, and treated HbSS RBCs (HbSS + Vox, HbSS + PKR, and HbSS + GBT021601) under normoxic and hypoxic conditions. Error bars are presented as SEM. ns, not significant; SEM, standard error of the mean; Vox, voxelotor.](https://ash.silverchair-cdn.com/ash/content_public/journal/bloodrci/1/2/10.1016_j.brci.2025.100015/3/brci_rci-2025-000108-gr1.jpeg?Expires=1763157810&Signature=2kHOsi3xhlWGchdaCur8HCsVz9BCDdcw4H7KqyJSeK-sQ8mvtp6AjE5Lggh9Dkupk1zCcdZkWUy5I0Ki6w9LKOYjHwsdN1D8n8iMTFZQchykFn6NsfRIxvV0zx-qhNx3br9OTHC3peCCVWzGaEEXi-blP-rN7d3iJOLlEdD3P3q9pyDRKfPigUxvQeM40ogoJqCKg7ntnG2jPGUZ2RViOyk6LpfpvkHz5S~JWRRA5CZdHpWiMSWfdv574DvjpIie4Ox5NJLn9WhZhcG0nhroFCV3TTfSp3G9J4eYKXVIwwJCHEAzNDbET0~0q~f4YR5XSp9~dveqUA4CtOtHtGyu8w__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA)
Vox, PKR activator, and GBT021601 reduce microcapillary occlusion in HbSS RBCs under normoxia and hypoxia. (A) OcclusionChip device used to assess RBC-mediated microcapillary occlusion under normoxic (pO2 ≈ 100 mm Hg) and mixed venous hypoxic (pO2 ≈ 44 mm Hg) conditions. (B) Microcapillary OI comparison between sickle (HbSS) and healthy (HbAA) RBCs under normoxia (HbAA [n = 8] vs HbSS [n = 15]; ∗∗∗P < .001) and hypoxia (HbAA [n = 8] vs HbSS [n = 15]; ∗∗∗P < .001, Mann-Whitney U test). (C) Under normoxia, treatment with Vox, PKR activator, or GBT021601 significantly reduced OI in HbSS RBCs (HbSS vs HbSS + Vox; HbSS vs HbSS + PKR; HbSS vs HbSS + GBT021601; n = 7; ∗P < .05; Wilcoxon test). (D) Similar reductions were observed under hypoxia (HbSS vs HbSS + Vox, n = 12 [∗∗∗P < .001]; HbSS vs HbSS + PKR, n = 12 [∗∗∗P < .001]; HbSS vs HbSS + GBT021601, n = 6 [∗∗∗P < .001]; Wilcoxon test). (E) Summary of mean ± SEM OI for HbAA, HbSS, and treated HbSS RBCs (HbSS + Vox, HbSS + PKR, and HbSS + GBT021601) under normoxic and hypoxic conditions. Error bars are presented as SEM. ns, not significant; SEM, standard error of the mean; Vox, voxelotor.
