If besides hemoglobin SS patients also have hemoglobin F in the erythrocytes, it reduces the degree of aggregation and crystallization of hemoglobin S, and as a result, they have fewer symptoms of sickle cell anemia or don’t have them at all. Increased levels of HbF slow down polymerization of deoxy sickle hemoglobin. HbF decreases HbS concentration, and together with its mixed hybrid tetramer (?2?S?) are not able to enter the deoxy sickle hemoglobin polymer phase. The antipolymerization effect of HbF resides primarily in HBG (both ?-globin genes) residues glycine ?87 and aspartic acid ?80. By inhibiting the tendency of deoxy sickle hemoglobin to polymerize, sufficient HbF thwarts the cellular damage evoked by HbS polymer.