title: Hydroxyurea therapy lowers transcranial Doppler flow velocities in children with sickle cell anemia.
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 (> or = 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.
authors.affiliation: Duke Pediatric Sickle Cell Program, and Division of Pediatric Hematology/Oncology, Duke University Medical Center, Durham, NC, USA.
authors.forename: Sherri A
authors.initials: SA
authors.lastname: Zimmerman
authors.forename: William H
authors.initials: WH
authors.lastname: Schultz
authors.forename: Shelly
authors.initials: S
authors.lastname: Burgett
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mortier
authors.forename: Russell E
authors.initials: RE
authors.lastname: Ware
mesh_terms: D000755:Anemia, Sickle Cell / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology* / Q000628:therapy; D000986:Antisickling Agents / Q000008:administration & dosage*; D001783:Blood Flow Velocity / Q000187:drug effects*; D001803:Blood Transfusion; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage*; D008297:Male; D020714:Maximum Tolerated Dose; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging; D011446:Prospective Studies; D020521:Stroke / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D000986:Antisickling Agents; D006918:Hydroxyurea