Oxygen delivery with and without voxelotor. (A) ODC. The in vivo whole-blood ODCs at a rate of oxygen pressure decrease of 40 torr/s were calculated in blood samples from 23 patients with SCD, using the solution ODC and the average composition in the legend to Figure 1 and the intracellular concentration distribution given in the inset to Figure 5B. The continuous blue curve is for blood with no drug; the continuous green curve is for blood with 26% of the Hb modified as found for the average modification in the clinical trials14 with reduced sickling (B). The dotted curves would be observed if polymerization were at equilibrium at every oxygen pressure. (B) Sickling. The fraction sickled vs time is calculated for whole blood without (blue) and with (green) voxelotor at a 26% modification of Hb. (C) Oxygen delivery. The fraction of oxygen delivered is calculated in 2 scenarios. The upper continuous blue and green curves correspond to the scenario where all cells contribute to oxygen delivery, whether or not the cells are sickled. The lower blue and green curves correspond to the scenario in which cells deliver oxygen until they sickle. At the sickling pressure and below, they stop delivering. For cells with bound drug, the Hb level is increased from 8.5 to 9.5 g/dL, to account for the increase observed in patients treated with the drug.14 The red curve is the oxygen delivery curve for normal blood (14 g/dL) at the top.