VARIATION IN FETAL HEMOGLOBIN PARAMETERS AND PREDICTED HEMOGLOBIN-S POLYMERIZATION IN SICKLE-CELL CHILDREN IN THE FIRST 2 YEARS OF LIFE - PARISIAN PROSPECTIVE-STUDY ON SICKLE-CELL DISEASE

Intracellular hemoglobin S (HbS) polymerization is most likely to be t he primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the H bS polymer and its intracellular expression in sickle erythrocytes inh ibits polymerization. HbF levels, high at birth but decreasing thereaf ter, protect the newborn from the clinical manifestations of this hemo globinopathy. We have measured the sequential changes in HbF, F reticu locytes, and F cells in the first 2 years of life in 25 children with SCD and compared the results with those obtained in 30 normal children (AA). We have also calculated HbF per F cell (F/F cell), the preferen tial survival of F cells Versus non-F cells, as measured by the ratio F cells versus F reticulocytes (FC/FR) and polymer tendency at 40% and 70% oxygen saturation. HbF levels decreased from about 80.4% +/- 4.0% at birth to 9.2% +/- 2.9% at 24 months. During this time, we observed a regular decrease of the F reticulocytes and the F cells. The kineti cs of the decline of F/F cell was comparable with the decline of HbF, rapid from birth (mean, 27.0 +/- 3.6 pg) to 12 months of age (mean, 8. 5 +/- 1.5 pg) and then slower from 12 to 24 months of age (mean, 6.2 /- 1.0 pg) in the SCD children. In the AA children, the decrease in Hb F, due to changes in both numbers of F cells and F/F cell, was more pr ecipitous, reaching steady-state revels by 10 months of age. Calculate d values for mean polymer tendency in the F-cell population showed tha t polymerization should begin to occur at 40% oxygen saturation at abo ut 3 months and increase progressively with age, whereas polymerizatio n at 70% oxygen saturation would not occur until about 24 months. Thes e values correspond to HbF levels of 50.8% +/- 10.8% and 9.2% +/- 2.9% , respectively, and F/F cell levels of 15.6 +/- 4.5 pg and 6.2 +/- 1.0 pg, respectively. In the non-F-cell population, polymerization was ex pected at birth at both oxygen saturation values. Three individuals ha d significantly greater predicted polymerization tendency than the rem ainder of the group because of early decreases in HbF, These individua ls in particular, the remainder of the cohort, as well as other recrui ted newborns, will be studied prospectively to ascertain the relations hip among hematologic parameters, which determine polymerization tende ncy and the various clinical manifestations of SCD. (C) 1994 by The Am erican Society of Hematology.