The effect of fetal hemoglobin on the survival characteristics of sickle cells

Abstract

The determinants of sickle red blood cell (RBC) life span have not been well-defined but may include both intrinsic factors (eg, the tendency to sickle) and extrinsic factors (eg, the capacity of the reticuloendothelial system to remove defective RBCs). Fetal hemoglobin (HbF) is heterogeneously distributed among sickle RBCs; F cells contain 20% to 25% HbF, whereas the remainder have no detectable HbF (non-F cells). Autologous sickle RBCs were labeled with biotin and reinfused to determine overall survival, non-F- and F-cell survival, and time-dependent changes in HbF content (%HbF) for the surviving F cells. A total of 10 patients were enrolled, including 2 who were studied before and after the percentage of F cells was increased by treatment with hydroxyurea. As expected, F cells survived longer in all subjects. Non-F-cell survival correlated inversely with the percentage of F cells, with the time for 30% cell survival ranging from 6 days in patients with more than 88% F cells to 16 days in patients with less than 16% F cells. As the biotin-labeled RBCs aged in the circulation, the HbF content of the surviving F-cell population increased by 0.28%/d +/- 0.21%/d, indicating that within the F-cell population those with higher HbF content survived longer.

Figure 1.

Percent survival. Survival is shown for F cells (♦) and non-F cells (□). The survival of each cell type was derived from the overall survival of biotin-labeled cells and the percentage of labeled F cells at each time point as described in “Materials and methods.” Each experiment is identified in accordance with Table 1.

Figure 2.

Survival of non-F cells in subjects with either a very low (less than 16%) or a very high (more than 88%) percentage of F cells.

Figure 3.

The 30% survival (time at which 30% of labeled cells remain) of non-F cells as a function of percent F cells in the circulation. Patients were either taking (□) or not taking (▴) HU. The dotted lines connect the points for 2 patients studied before and after treatment with hydroxyurea.

Figure 4.

Change in percent HbF in the rermaining F-cell population as a function of time after reinfusion for a representative patient. The open circles represent biotin-labeled RBCs, and the open squares represent unlabeled RBCs. The slope for labeled RBCs is the rate of increase in F-cell HbF (percent per day).

Figure 5.

HbF in F cells. The rate of increase of percent HbF in F cells for the surviving population of labeled cells (B-RBC) and unlabeled cells (RBC). n = 12, P < .005.