Hydroxyurea therapy lowers transcranial Doppler flow velocities in children with sickle cell anemia

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Abstract
Hydroxyurea has hematologic and clinical efficacy in sickle cell anemia (SCA), but its effects on transcranial Doppler (TCD) flow velocities remain undefined. Fifty-nine children initiating hydroxyurea therapy for clinical severity had pretreatment baseline TCD measurements; 37 with increased flow velocities (≥ 140 cm/s) were then enrolled in an institutional review board (IRB)–approved prospective phase 2 trial with TCD velocities measured at maximum tolerated dose (MTD) and one year later. At hydroxyurea MTD (mean ± 1 SD = 27.9 ± 2.7 mg/kg per day), significant decreases were observed in the right middle cerebral artery (MCA) (166 ± 27 cm/s to 135 ± 27 cm/s, P < .001) and left (MCA) (168 ± 26 cm/s to 142 ± 27 cm/s, P < .001) velocities. The magnitude of TCD velocity decline was significantly correlated with the maximal baseline TCD value. At hydroxyurea MTD, 14 of 15 children with conditional baseline TCD values improved, while 5 of 6 with abnormal TCD velocities whose families refused transfusions became less than 200 cm/s. TCD changes were sustained at follow-up. These prospective data indicate that hydroxyurea can significantly decrease elevated TCD flow velocities, often into the normal range. A multicenter trial is warranted to determine the efficacy of hydroxyurea for the management of increased TCD values, and ultimately for primary stroke prevention in children with SCA.