Effect of Hydroxyurea on Patient with High Fetal Hemoglobin Expression

High Fetal Hemoglobin (Hb F) expression in Sickle Cell Disease (SS), when first described, was defined as an "entirely benign disorder", due to its less severe manifestations; protective levels were described as 10 pg or more (AJCD, 133:1248, 1979). Continued high expression of Hb F as hereditary persistence of fetal hemoglobin (HPFH) occurs in 0.1% of African-American individuals. Other individuals may not have compound heterozygosity for Hemoglobin S and gene deletion HPFH but still have haplotypic differences resulting in higher HbF levels. We performed an IRB-approved chart review looking at SS patients with High HbF, followed at Children's Hospital from 2005-2020. We identified 13 children, 4-20 years, having mean HbF levels of 22.14 +/- 4.9%. Two children were considered inevaluable for analysis due to one being on voxelotor and the other being on chronic transfusion at the time of analysis. Of the 11 children remaining for analysis, 8 were girls and 3 boys. Complications requiring hospitalization included: acute chest syndrome, VOE, stroke including occult, osteomyelitis, aplastic crisis. Surgeries included osteotomy, cholecystectomy, and tonsillectomy/adenoidectomy. Eight children were placed on hydroxyurea (HU). After HU, total Hb and HbF did not significantly change (Hb 7.08+/-1.27 vs 8.97+/-1.55;HbF 22.4 +/-4.9 pre to 18.9+/-6.6, respectively). Admission or hospitalization frequency (admits or hospital stays/years studied) were evaluated, as were ED visits/years studied for SS-related problems. These data were: 1.36+/-0.51 pre vs. 0.4+/-0.46 post (for admits); 1.52+/-0.32 pre vs 0.33+/-0.21 post (for ED visits) p<0.05 for both). Three individuals were not on HU with an annual admission frequency of .75-1.2 and 1-3.2 for ED visits. The limitations of this study are: small n, lack of serologic proof of HU compliance, difficulties with data retrieval. Although the sample size is small, however, there does appear to be a salutary effect of HU on hospitalizations or vasoocclusive events after placement of these children on HU. Current recommendations to begin HU in children with SS at 9 months of age appear to have validation even in children with high HbF. We used the Kleihauer-Betke stain for HPFH diagnosis in most instances since gene analysis was not available to us due to insurance restraints; we acknowledge the need for genetic analysis to determine whether these individuals are "high F" or HPFH patients. Moderation of clinical course is dependent not only on HbF levels (which did not show significant increment after HU), but also on decreased WBC and platelet count with associated decreased inflammation and hypercoagulability.

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