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Updated: Dec 26, 2025
A Precision Medicine Tool for Measurement and Monitoring of Hemoglobin S in Sickle Cell Disease Patients Receiving Transfusion Therapy
Laboratory Biomarkers, Cerebral Blood Flow Velocity, and Intellectual Function in Children with Sickle Cell Disease
Nataly Apollonsky1, Norma B Lerner2, Fengqing Zhang3
1Section of Hematology, St. Christopher's Hospital for Children, Philadelphia, PA, USA.
Insights
In children with sickle cell disease (SCD), markers of blood vessel damage and inflammation, not blood flow speed, are linked to cognitive function. Hydroxyurea treatment may help prevent cognitive decline.
Area of Science:
- Pediatric Neurology
- Hematology
- Neuroscience
Background:
- Sickle cell disease (SCD) is associated with an increased risk of cerebrovascular complications.
- Cerebral vasculopathy, characterized by abnormal blood vessel function, is a known complication in SCD.
- Understanding factors influencing cognitive function in children with SCD is crucial for early intervention.
Purpose of the Study:
- To identify markers of cerebral vasculopathy in children with SCD.
- To investigate the relationship between these markers, demographic factors, and cognitive function.
- To explore the role of blood flow velocity and specific biomarkers in predicting cognitive outcomes.
Main Methods:
- A preliminary study included 38 children with homozygous HbS (sickle cell anemia), aged 4-11 years.
- Data collected included estimated IQ, markers of coagulation, endothelial activation, hemolysis, inflammation, and transcranial Doppler (TCD) velocities.
- Hydroxyurea (HU) use and demographic information were also obtained.
Main Results:
- Few significant independent associations were found between most biomarkers or blood flow velocity and estimated IQ.
- Lactic dehydrogenase (LDH) independently predicted cognitive function, but TCD velocities did not mediate this.
- Maternal education, patient age, and HU status were significant predictors of cognition. A LASSO model identified LDH, absolute neutrophil count (ANC), platelet count, thrombin-antithrombin (TAT), tissue factor (TF), maternal education, age, and HU as potential predictors.
Conclusions:
- Vasculopathic markers, particularly intravascular hemolysis and coagulation/endothelial activation, are associated with cognitive function in young children with SCD, independent of blood flow velocity.
- Age and maternal education are also key factors influencing cognitive outcomes.
- Further research is warranted to explore the role of these markers and hydroxyurea treatment in preventing or reversing cognitive decline in children with SCD.
Objective:
The aim of this preliminary study was to describe putative markers of cerebral vasculopathy and investigate relationships among these markers, demographic factors, and cognitive function in a young sample of neurologically normal children with SCD. Study Design. Thirty-eight children with homozygous HbS, aged 4-11 years, were included. Estimated IQ and markers of coagulation and endothelial activation, hemolysis, and inflammation, as well as transcranial Doppler velocities, hydroxyurea use, and demographic information were obtained.
Results:
Using multiple regression analyses, there were few significant independent associations between biomarkers or blood flow velocity and estimated IQ. Lactic dehydrogenase (LDH) independently predicted cognitive function, but blood flow velocity did not mediate this relationship. Maternal education, patient age, and hydroxyurea status were independent predictors of cognition. Given the small sample size, a LASSO statistical model was employed to further identify potential predictors of IQ, which identified LDH, absolute neutrophil count (ANC), platelet count, thrombin-antithrombin (TAT), tissue factor (TF), maternal education, age, and hydroxyurea as potential predictors of cognition.
Conclusions:
In addition to effects of age and maternal education, some vasculopathic markers are associated with cognitive function in young children with SCD, and these relationships do not appear to be mediated through blood flow velocity. Although the lack of association among certain variables was not as predicted, results provide support for further research regarding the influence of vasculopathic markers on cognitive function in children with SCD without stroke, especially intravascular hemolysis and coagulation/endothelial activation, and a possible role for HU treatment in preventing or reversing cognitive decline.
