Hydroxyurea to decrease stroke risk in children with sickle cell anemia: a systematic review and meta-analysis

Area of Science:

• Pediatric Hematology
• Neurology
• Pharmacology

Background:

• Sickle cell anemia (SCA) is an inherited disorder leading to stroke in children.
• Transcranial Doppler (TCD) ultrasound assesses stroke risk in SCA patients.
• Current stroke prevention includes transfusions, which have limitations in resource-limited settings.

Purpose of the Study:

• To systematically review the effectiveness of hydroxyurea in reducing TCD velocities and stroke risk in children with SCA.
• To clarify the effect size and duration of hydroxyurea's impact on TCD velocities.

Main Methods:

• A systematic review of prospective clinical trials was conducted across five major medical databases.
• Included trials enrolled children with SCA, used TCD screening, and collected serial TCD velocity and stroke incidence data during hydroxyurea therapy.
• Data from 13 trials involving 592 participants were analyzed.

Main Results:

• Hydroxyurea significantly decreased mean TCD velocities by -30 cm/s over 0.5 to 2.6 years, with normalization in most children.
• Stroke incidence was low (0.52-1.92 per 100 patient-years) and occurred only in those with persistently high TCD values (>200 cm/s).
• Hydroxyurea demonstrated effectiveness in reducing TCD velocities and associated stroke risk.

Conclusions:

• Hydroxyurea is an effective strategy for mitigating stroke risk in pediatric SCA by reducing TCD velocities.
• It presents a feasible alternative to blood transfusions, particularly beneficial in resource-limited healthcare settings.
• Further research is warranted to optimize dosing, assess long-term safety, and evaluate comprehensive benefits across diverse populations.