Fetal hemoglobin in sickle cell anemia: a glass half full?
Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia by inhibiting deoxy sickle hemoglobin (HbS) polymerization. The blood concentration of HbF, or the number of cells with detectable HbF (F-cells), does not measure the amount of HbF/F-cell. Even patients with high HbF can have severe disease because HbF is unevenly distributed among F-cells, and some cells might have insufficient concentrations to inhibit HbS polymerization. With mean HbF levels of 5%, 10%, 20%, and 30%, the distribution of HbF/F-cell can greatly vary, even if the mean is constant. For example, with 20% HbF, as few as 1% and as many as 24% of cells can have polymer-inhibiting, or protective, levels of HbF of ∼10 pg; with lower HbF, few or no protected cells can be present. Only when the total HbF concentration is near 30% is it possible for the number of protected cells to approach 70%. Rather than the total number of F-cells or the concentration of HbF in the hemolysate, HbF/F-cell and the proportion of F-cells that have enough HbF to thwart HbS polymerization is the most critical predictor of the likelihood of severe sickle cell disease.
Center of Excellence in Sickle Cell Disease, Department of Medicine, Boston University School of Medicine, Boston, MA;
Martin H
MH
Steinberg
David H K
DH
Chui
George J
GJ
Dover
Paola
P
Sebastiani
Abdulrahman
A
Alsultan
D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood / Q000276:immunology* / Q000628:therapy*; D004912:Erythrocytes / Q000166:cytology; D005319:Fetal Hemoglobin / Q000276:immunology*; D017353:Gene Deletion; D006239:Haplotypes; D006451:Hemoglobin, Sickle / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D008962:Models, Theoretical; D005810:Multigene Family; D010641:Phenotype; D011108:Polymers / Q000737:chemistry
D006451:Hemoglobin, Sickle; D011108:Polymers; D005319:Fetal Hemoglobin; D006918:Hydroxyurea