Prevention of secondary stroke and resolution of transfusional iron overload in children with sickle cell anemia using hydroxyurea and phlebotomy

J Pediatr. 2004 Sep;145(3):346-52. doi: 10.1016/j.jpeds.2004.04.058.

Abstract

Objective: Transfusions prevent secondary stroke in children with sickle cell anemia (SCA) but also cause iron overload. Alternatives for stroke prophylaxis with effective therapy to reduce iron burden are needed.

Study design: For 35 children with SCA and stroke, transfusions were prospectively discontinued. Hydroxyurea was prescribed for stroke prophylaxis, and phlebotomy removed excess iron. Initial patients discontinued transfusions before hydroxyurea therapy, but later patients overlapped transfusions with hydroxyurea until tolerating full-dose therapy.

Results: Children received hydroxyurea for 42 +/- 30 months (range, 3-104 months). Hydroxyurea (26.7 +/- 4.8 mg/kg per day) led to mild neutropenia (3.9 +/- 2.3 x 10(9)/L) with significant increases in hemoglobin concentration, mean corpuscular volume, and fetal hemoglobin. Stroke recurrence rate was 5.7 events per 100 patient-years, but children receiving overlapping hydroxyurea therapy had only 3.6 events per 100 patient-years. For 26 children with >6 months of phlebotomy, 14,311 +/- 12,459 mL blood (315 +/- 214 mL/kg) was removed, with serum ferritin decreasing from a median of 2722 to 298 ng/mL. Among patients completing phlebotomy, liver biopsy documented normal histology and no excess iron deposition.

Conclusions: For children with SCA and stroke, hydroxyurea effectively prevents secondary stroke and serial phlebotomy leads to complete resolution of transfusional iron overload.

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / drug therapy*
  • Antisickling Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Humans
  • Hydroxyurea / therapeutic use*
  • Infant
  • Iron Overload / therapy
  • Male
  • Phlebotomy
  • Prospective Studies
  • Secondary Prevention
  • Stroke / etiology
  • Stroke / prevention & control*

Substances

  • Antisickling Agents
  • Hydroxyurea