Physiologic decline in fetal hemoglobin parameters in infants with sickle cell disease: implications for pharmacological intervention.
OBJECTIVE
Fetal hemoglobin (HbF) is an important determinant in the clinical severity of patients with sickle cell disease. The physiologic decline in HbF parameters in a cohort of infants with sickle cell disease was investigated.


METHODS
The percent HbF and F cells were quantitated, and the HbF per F cell was then calculated. One hundred thirty-eight blood samples from 44 infants with homozygous sickle cell anemia (HbSS) and 56 samples from 24 infants with sickle cell hemoglobin (HbSC) were studied.


RESULTS
Infants with HbSS had a logarithmic decline in HbF parameters; at 24 months, the average HbF was 14.6%+/-7.3% and the % F cells was 64.7%+/-16.9%. The amount of HbF in each F cell (HbF per F cell) was <15 pg/cell, a suggested threshold for intracellular sickle polymerization, by age 12 months. Infants with HbSC had a more rapid decline: at 12 months the average % HbF was 12.2%+/-9.3%, the % F cells was 60.5%+/-18.7%, and the HbF per F cell was <10 pg/cell.


CONCLUSIONS
By age 2 years, HbF parameters including the % HbF, % F cells, and the HbF per F cell decrease to levels insufficient to inhibit sickling. Pharmacologic intervention designed to enhance HbF production and prevent chronic organ damage should be considered during infancy.
Marcus
S J
SJ
Duke Pediatric Sickle Cell Program, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Ware
R E
RE
D000375:Aging / Q000097:blood; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D000986:Antisickling Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005319:Fetal Hemoglobin / Q000378:metabolism*; D006444:Hemoglobin C / Q000378:metabolism; D006451:Hemoglobin, Sickle / Q000235:genetics / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D007223:Infant; D008297:Male
D000986:Antisickling Agents; D006451:Hemoglobin, Sickle; D006444:Hemoglobin C; D005319:Fetal Hemoglobin; D006918:Hydroxyurea