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• W2433440883 abstract "Hydroxyurea is one of several cytostatic agents that increase fetal hemoglobin (HbF) production in some patients with sickle-cell disease, although their mechanisms of action remain to be defined. We have studied the effects of hydroxyurea in several hospitalized patients with sickle-cell disease treated for 3 months, who were then maintained on outpatient therapy. Among hydroxyurea-treated patients, we found that about 75% respond with at least a twofold increase in the percentages of F reticulocytes and HbF. Among the responders, HbF levels increased twofold to 10-fold, with three patients achieving levels of 10% to 15%. Statistical analysis of the three cellular variables that determine HbF levels in patients with sickle-cell disease--namely, increased F-cell production, F-cell survival, and HbF/F cells--disclosed that HbF production, as measured by an increase in F reticulocytes, accounted for about 70% of the HbF elevation, with smaller contributions coming from augmentation of HbF/F cells and preferential survival of F cells. Four responders were re-treated with their optimal weekly hydroxyurea dose, given either in daily fractions or over 4 consecutive days, after a 1- to 3-month washout period. Greater HbF responses were attained with the optimal hydroxyurea dose than with the dose-regimen escalation, and usually occurred after a lag period. Furthermore, increases in HbF and F-cell levels were more rapid in patients receiving therapy on 4 out of 7 days rather than on a daily schedule. Our calculations show that the increases in HbF/F and F cells and the decrease in the fraction of dense cells during limited hydroxyurea administration should cause a significant improvement in intracellular sickle hemoglobin polymerization tendency. Controlled prospective trials are necessary to establish whether these effects lead to clinical benefit. Alternate schedules of hydroxyurea administration, or its use in conjunction with other means to elevate HbF or reduce mean cell hemoglobin concentration, may achieve greater inhibition of polymerization and thus be more likely to result in unequivocal amelioration of disease manifestations." @default.
• W2433440883 created "2016-06-24" @default.
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• W2433440883 date "1992-06-01" @default.
• W2433440883 modified "2023-10-18" @default.
• W2433440883 title "Spectrum of fetal hemoglobin responses in sickle cell patients treated with hydroxyurea: the National Institutes of Health experience." @default.
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