Long-term results using hydroxyurea/phlebotomy for reducing secondary stroke risk in children with sickle cell anemia and iron overload

Am J Hematol. 2011 Apr;86(4):357-61. doi: 10.1002/ajh.21986.


Children with sickle cell anemia (SCA) and a primary overt stroke are at high risk of recurrent (secondary) stroke. Chronic transfusion therapy dramatically reduces but does not eliminate this high risk, and inevitably results in transfusion-related hemosiderosis. We previously reported the use of hydroxyurea/phlebotomy as an alternative to transfusions to reduce the risk of secondary stroke and improve management of iron overload in 35 children with SCA. To report long-term results, we retrospectively reviewed clinical and laboratory data through October 2008. With a median of 5.6 years and total of 219 patient-years of follow-up, 10 of 35 patients (29%) had recurrent stroke after switching to hydroxyurea; seven were previously reported and three new strokes occurred during extended follow-up. The overall secondary stroke event rate was 4.6 per 100 patient-years. Children on hydroxyurea received serial phlebotomy and had lower mean serum ferritin values than children on transfusions (591 ng/mL vs. 3410 ng/mL, P = 0.02). In this cohort, long-term hydroxyurea treatment reduced but did not eliminate the risk of stroke recurrence and, uniquely, allowed phlebotomy to reduce iron overload. Long-term assessments of this therapy should evaluate risk factors for secondary stroke and assessments of hemosiderosis, neurocognitive outcome, and health-related quality of life.

MeSH terms

  • Adolescent
  • Adult
  • Anemia, Sickle Cell / complications
  • Anemia, Sickle Cell / therapy*
  • Antisickling Agents / administration & dosage
  • Antisickling Agents / therapeutic use*
  • Child
  • Cohort Studies
  • Combined Modality Therapy
  • Follow-Up Studies
  • Humans
  • Hydroxyurea / administration & dosage
  • Hydroxyurea / therapeutic use*
  • Iron Overload / etiology
  • Iron Overload / therapy*
  • Male
  • Medical Records
  • Phlebotomy / methods*
  • Retrospective Studies
  • Risk
  • Secondary Prevention
  • Stroke / prevention & control*
  • Time Factors
  • Transfusion Reaction
  • Young Adult


  • Antisickling Agents
  • Hydroxyurea