Comparison of oxygen delivery by 3 therapeutic approaches. (A) ODC. The in vivo whole-blood ODCs at a rate of oxygen pressure decrease of 40 torr/s were calculated for blood samples from patients with SCD, by using the solution ODC, the average composition, and the average concentration distribution of the inset in Figure 5B. The continuous green curve is for blood with 26% of the Hb modified, as found for the average modification in the clinical trials.¹⁴ The continuous orange curves depict blood where a hypothetical drug has increased HbF from 8% to 35%, a percentage thought to be effectively curative.⁶² The dashed black curve depicts blood with a decrease in the MCHC by ∼ 10% from 35 to 31 g/dL. (B) Sickling. The fraction of cells sickled vs rapidly decreasing pressure for the 3 therapeutic approaches: (1) voxelotor at a 26% modification (green curve), (2) an increase in Hb F from 8% to 35% (orange curve), and (3) a decrease in MCHC from 35 to 31 g/dL (black dotted curve). (C) Oxygen delivery for all 3 approaches at the same Hb level of 9.5 g/dL. The upper and lower curves for each of the the 3 approaches correspond to the 2 scenarios described previously and in the legend to Figure 6C.