Hydroyxurea improves cerebral oxygen saturation in children with sickle cell anemia

Am J Hematol. 2021 May 1;96(5):538-544. doi: 10.1002/ajh.26120. Epub 2021 Feb 19.

Abstract

Neurologic complications are common in patients with sickle cell anemia (SCA), but conventional tools such as MRI and transcranial Doppler ultrasonography (TCD) do not fully assess cerebrovascular pathology. Cerebral tissue oximetry measures mixed oxygen saturation in the frontal lobes (SCT O2 ) and provides early prognostic information about tissue at risk of ischemic injury. Untreated patients with SCA have significantly lower SCT O2 than healthy controls that declines with age. Hydroxyurea is effective in preventing many SCA-related complications, but the degree to which it preserves normal neurophysiology is unclear. We analyzed participants enrolled in the Therapeutic Response Evaluation and Adherence Trial (TREAT, NCT02286154), which enrolled participants initiating hydroxyurea using individualized dosing (new cohort) and those previously taking hydroxyurea (old cohort) and was designed to monitor the long-term benefits of hydroxyurea. Cerebral oximetry was performed at baseline and annually. For the new cohort (median starting age = 12 months, n = 55), mean baseline SCT O2 was normal before starting hydroxyurea (mean 65%, 95% CI 58-72%) and significantly increased after 2 years (mean 72%, 95% CI 65-79%, p < .001). The SCT O2 for patients receiving long-term hydroxyurea (median age = 9.6 years) was normal at study entry (mean 66%, 95% CI 58-74%) and remained stable across 2 years. Both cohorts had significantly higher SCT O2 than published data from predominantly untreated SCA patients. Cerebral oximetry is a non-invasive method to assess cerebrovascular pathology that complements conventional imaging. Our results indicate that hydroxyurea suggests protection against neurophysiologic changes seen in untreated SCA.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anemia, Sickle Cell / blood
  • Anemia, Sickle Cell / drug therapy*
  • Anemia, Sickle Cell / physiopathology
  • Antisickling Agents / administration & dosage
  • Antisickling Agents / pharmacokinetics
  • Antisickling Agents / pharmacology
  • Antisickling Agents / therapeutic use*
  • Cerebrovascular Circulation / drug effects*
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Early Medical Intervention
  • Female
  • Humans
  • Hydroxyurea / administration & dosage
  • Hydroxyurea / pharmacokinetics
  • Hydroxyurea / pharmacology
  • Hydroxyurea / therapeutic use*
  • Infant
  • Male
  • Oximetry / instrumentation
  • Oximetry / methods*
  • Oxygen / blood
  • Oxyhemoglobins / analysis
  • Precision Medicine
  • Prospective Studies
  • Young Adult

Substances

  • Antisickling Agents
  • Oxyhemoglobins
  • Oxygen
  • Hydroxyurea