Maier-Redelsperger M, Noguchi C T, de Montalembert M, Rodgers G P, Schechter A N, Gourbil A, Blanchard D, Jais J P, Ducrocq R, Peltier J Y
Laboratoire d'Hématologie, Hôpital Tenon, Paris, France.
Blood. 1994 Nov 1;84(9):3182-8.
Intracellular hemoglobin S (HbS) polymerization is most likely to be the primary determinant of the clinical and biologic manifestations of sickle cell disease (SCD). Fetal hemoglobin (HbF) does not enter the HbS polymer and its intracellular expression in sickle erythrocytes inhibits polymerization. HbF levels, high at birth but decreasing thereafter, protect the newborn from the clinical manifestations of this hemoglobinopathy. We have measured the sequential changes in HbF, F reticulocytes, 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 preferential 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 kinetics 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 HbF, due to changes in both numbers of F cells and F/F cell, was more precipitous, reaching steady-state levels by 10 months of age. Calculated values for mean polymer tendency in the F-cell population showed that polymerization should begin to occur at 40% oxygen saturation at about 3 months and increase progressively with age, whereas polymerization at 70% oxygen saturation would not occur until about 24 months. These 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 expected at birth at both oxygen saturation values. Three individuals had significantly greater predicted polymerization tendency than the remainder of the group because of early decreases in HbF. These individuals in particular, the remainder of the cohort, as well as other recruited newborns, will be studied prospectively to ascertain the relationship among hematologic parameters, which determine polymerization tendency and the various clinical manifestations of SCD.
细胞内血红蛋白S（HbS）聚合很可能是镰状细胞病（SCD）临床和生物学表现的主要决定因素。胎儿血红蛋白（HbF）不会进入HbS聚合物，其在镰状红细胞内的表达可抑制聚合。HbF水平在出生时较高，但随后逐渐下降，可保护新生儿免受这种血红蛋白病临床表现的影响。我们测量了25名SCD儿童出生后2年内HbF、F网织红细胞和F细胞的连续变化，并将结果与30名正常儿童（AA）的结果进行了比较。我们还计算了每个F细胞的HbF（F/F细胞）、F细胞与非F细胞相比的优先存活率，通过F细胞与F网织红细胞的比率（FC/FR）以及在40%和70%氧饱和度下的聚合倾向来衡量。HbF水平从出生时的约80.4%±4.0%降至24个月时的9.2%±2.9%。在此期间，我们观察到F网织红细胞和F细胞呈规律性下降。SCD儿童中F/F细胞下降的动力学与HbF的下降相当，从出生时（平均27.0±3.6 pg）到12个月龄（平均8.5±1.5 pg）迅速下降，然后从12至24个月龄（平均6.2±1.0 pg）下降较慢。在AA儿童中，由于F细胞数量和F/F细胞的变化导致的HbF下降更为急剧，到10个月龄时达到稳态水平。F细胞群体中平均聚合倾向的计算值表明，在约3个月时，在40%氧饱和度下聚合应开始发生，并随年龄逐渐增加，而在70%氧饱和度下的聚合直到约24个月才会发生。这些值分别对应于HbF水平50.8%±10.8%和9.2%±2.9%，以及F/F细胞水平15.6±4.5 pg和6.2±1.0 pg。在非F细胞群体中，预计在出生时两种氧饱和度值下都会发生聚合。由于HbF早期下降，三名个体的预测聚合倾向明显高于该组其他个体。将对这些个体、该队列的其余部分以及其他招募的新生儿进行前瞻性研究，以确定血液学参数之间的关系，这些参数决定了聚合倾向和SCD的各种临床表现。
