Schematic illustrating the HVR as a function of hematocrit for patients with SS hemoglobin (untreated), SS hemoglobin (treated with hydroxyurea or chronic transfusions), and AA hemoglobin. HVR is a metric of the microvascular oxygen-delivery potential and balances the positive effects of increased oxygen delivery vs the negative effects of increased viscosity. The hematocrit that optimizes HVR, as well as the peak HVR obtained, is lower in patients with SS compared with those with AA hemoglobin. In SCD, effective therapies must not only increase hemoglobin but improve red cell rheology.