An investigation into the natural history of transcranial Doppler velocities in an East London cohort of children with sickle cell disease aged between 2 and 16

Ngwa-Ndifor, Naavalah (2025) An investigation into the natural history of transcranial Doppler velocities in an East London cohort of children with sickle cell disease aged between 2 and 16. Doctoral thesis (DClinSci), Manchester Metropolitan University.

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Abstract

Background – Children with sickle cell disease (SCD) in the UK are at significantly increased risk of stroke, particularly between ages 2 – 5. Transcranial Doppler (TCD) ultrasound is used from age 2 to detect intracranial arterial narrowing, enabling risk stratification via STOP classification. Barts Health hosts a large paediatric SCD cohort with longitudinal TCD data. Aim – To compare imaging and non-imaging TCD velocity measurements; assess whether sex, age, oxygen saturation, and haemoglobin concentration affect TCD velocities; and evaluate changes in STOP classifications over time in this East London paediatric SCD cohort. Methods – Study 1: 18 adults underwent both imaging and non-imaging TCD, with time-averaged mean of the maximum velocity (TAMMV) recorded in the middle cerebral artery (MCA), anterior cerebral artery (ACA) and terminal internal carotid artery (tICA) bilaterally. Study 2: Retrospective analysis of 1664 TCDs from 224 children aged 2 – 16 years with HbSS and ≥2 TCDs from the SCD Cohort Database (2010–2023). Highest TAMMV was examined for differences, correlations and predictive value using standard non-parametric tests and linear regression. Results – Study 1: Non-imaging TCD produced significantly higher velocities than imaging TCD in all arteries. Study 2: Females had higher TAMMVs and haemoglobin levels. A negative correlation was found between haemoglobin and TAMMV (p < 0.001). Normal STOP classifications were associated with higher haemoglobin (8.7 g/dL) than conditional/abnormal classifications (8.1 g/dL). Each 1 g/dL increase in haemoglobin predicted a 6.07 cm/s reduction in TAMMV. Conditional and abnormal STOP results declined from 40.3% and 14.5% in 2013 to 16.9% and 2.3% in 2022, respectively. Conclusion – Imaging TCD records lower velocities than non-imaging TCD, though findings were affected by technical errors. Further validation is needed in paediatric populations. Haemoglobin concentration is a strong predictor of TCD velocity and STOP category. The decreasing prevalence of abnormal and conditional STOP results, may reflect improved clinical management, including hydroxyurea use but further study is warranted. Keywords: sickle cell disease (SCD), transcranial Doppler (TCD), STOP classification, haemoglobin concentration, imaging vs non-imaging TCD, TCD velocity (TAMMV), paediatric stroke risk