Sickle erythrocytes are a mixture of cells with measurable HbF (F cells) and non-F cells. F cells are long lived, do not acquire the same increment of HbS-induced damage as non-F cells, are less likely to initiate adhesive events, and are associated with protection from sickle vaso-occlusion (left arrow). The heterocellular distribution of HbF in sickle cell anemia, even when total HbF concentrations are high at baseline or in response to hydroxyurea, means that some erythrocytes with no HbF or with suboptimal concentrations of HbF are present. Some of these cells hemolyze intravascularly liberating hemoglobin, which scavenges nitric oxide and contributes to certain vascular complications of this disease (right arrow). This might account for the failure of high HbF that is heterocellularly distributed to protect against all disease complications.