Hydroyxurea improves cerebral oxygen saturation in children with sickle cell anemia

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 (SCTO2) and provides early prognostic information about tissue at risk of ischemic injury. Untreated patients with SCA have significantly lower SCTO2 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 SCTO2 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 SCTO2 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 SCTO2 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.

Role of hydroxyurea therapy in the prevention of organ damage in sickle cell disease: a systematic review and meta-analysis

“…In a study by Tavakkoli F et al involving 31 SCD patients, which measured near-infrared spectroscopy (NIRS) to determine cerebral oxygen saturation, it was observed that cerebral oxygen saturation was significantly higher in SCD patients on hydroxyurea therapy than in those not on hydroxyurea therapy (46.1 ± 6.6 vs 41.2 ± 7.6, p < 0.025) [ 40 ]. Another study by Karkoska K et al showed that cerebral oxygen saturation significantly increased after 2 years of hydroxyurea therapy in 55 SCD patients (65 to 72%, p < 0.001) [ 41 ]. A study by Kapustin D et al among 27 SCD patients, showed that the mean white matter cerebrovascular reactivity was higher in hydroxyurea-treated patients compared to those who were not treated.…”

The Impact of Hydroxyurea Use on Cognitive Functioning of Children with Sickle Cell Disease Living in Ghana

“…This is supported by a prospective study that showed stable or improved cerebral oxygen saturation in patients on hydroxyurea compared to those not on the drug. [28] Additionally, hydroxyurea use has been shown to reduce cerebral blood flow, which has been demonstrated to be inversely proportional to performance IQ and working memory. [29,30] Finally, hydroxyurea may improve cognitive functioning by reducing hospitalizations for complications of SCD, thereby improving quality of life, schooling and attainment of developmental milestones.…”

Effect of Blood Transfusion on Cerebral Hemodynamics and Vascular Topology Described by Computational Fluid Dynamics in Sickle Cell Disease Patients

“…In addition to the improvement in vessel tortuosity and wall shear stress, this is also likely due to an increase in both total hemoglobin and improved oxygen carrying capacity with hemoglobin A, as well as lower cerebral blood flow velocity, allowing for better perfusion of the watershed areas of the brain, which are particularly susceptible to SCI. Hydroxyurea is speculated to work in a similar way to cRBC transfusions by also increasing total hemoglobin and increasing oxygen-carrying capacity through an increase in fetal hemoglobin [ 50 , 51 , 52 ].…”