Systematic Transcranial Doppler Examination in Adults with Sickle Cell Disease : A Cross-Sectional Single Center Study

Background

Individuals with sickle cell disease (SCD) are at a high risk of stroke throughout their lifespan. Regular transcranial doppler (TCD) screening is widely adopted for children with SCD to identify those in need of treatment intensification. However, TCD screening is not routinely performed beyond ages 16-18. Data on TCD feasibility and standard velocities in adults with SCD are limited. Since 2021, all adults with SCD followed at the Centre Hospitalier de l'Université de Montréal (CHUM) Comprehensive SCD Centre are referred for TCD examination as part of routine neurovascular surveillance, regardless of their genotype, age, comorbidities, or neurologic status.

ObjectivesThe primary aim of this study is to determine the feasibility of TCD in unselected adults with SCD. The secondary aim is to report the distribution of Doppler velocities in this population. We also aimed to explore associations between these measures and biological and clinical patient characteristics.

Methods In this retrospective study, clinical data of all patients seen at the SCD Center between September 2021 and June 2024 were reviewed and extracted.Patients with routine TCD examination were included in the study sample. Mean flow velocity (MFV) measurements were attempted in all patients for the anterior cerebral artery (ACA), the middle cerebral artery (MCA), the posterior cerebral artery (PCA), and the basilar artery (BasA). Feasibility was assessed using the following definitions: “standard TCD” with successful insonation of both MCA, and “complete TCD” for successful insonation of bilateral MCA, ACA, PCA and BasA. Chi-squared test was used to compare feasibility across predetermined groups (age, sex, genotype and body mass index (BMI)). Distribution of MFV was calculated as mean ± standard deviation (SD). A priori determined covariates tested for univariate linear association with MFV were age, sex, genotype, BMI, hemoglobin (Hb) and hematocrit (Hct). The project was approved by the local ethics committee.Results

A total of 249 SCD patients with a documented TCD examination were analyzed (mean age 35 [range 18 to 79 years], 141 (57%) were women). Overall, 115 (46%) patients had a SS/Sβ⁰ and 134 (54%) a SC/Sβ⁺ genotype. A prior diagnosis of cognitive disorder was present in 4 (2%), and of stroke in 19 (8%) cases. A majority of 156 patients (63%) were on hydroxyurea (HU) treatment alone, while 65 (26%) were on transfusions, and 18 (7%) on both treatments.

A “standard” TCD examination was feasible in 229 (92%) patients, while a “complete” TCD was successfully documented in 190 (76%). There was no statistically significant effect of sex, age, genotype and BMI on TCD feasibility.

Documented MFV (±SD) for cerebral arteries were as follows:

• MCA

  left 67 (±19) cm/s; right 67 (±19) cm/s;

• ACA

  left 53 (±16) cm/s; right 52 (±15) cm/s;

• PCA

  left 37 (±12) cm/s; right 38 (±12) cm/s;

• BasA

  43 (±14) cm/s

Linear regression showed increasing age was inversely associated with MFV in all arteries (p≤0.002). For each additional 10 years, a decrease of MFV (±SD) in the respective brain arteries was as follows:

• MCA

  left -4.8 (±1.0); right -3.6 (±1.0) cm/s;

• ACA

  left -3.1 (±1.0); right -2.9 (±0.9) cm/s;

• PCA

  left -2.6 (±0.7); right -2.2 (±0.7) cm/s;

• BasA

  -3.3 (±0.7) cm/s.

Female sex was associated with higher MFV in the left ACM and both PCA (p<0.05). MFV were negatively correlated with Hb and Hct for all arteries (p<0.005 for all). MFV were higher in the HbSS/Sβ⁰, compared to the HbSC/Sβ⁺ group (p<0.05).

Conclusion :

Our study showed that TCD can be implemented in routine follow-up of adult patients with SCD with a high (92%) success rate for standard MCA evaluation. Overall, measured intracranial velocities were in line with previously established patterns showing an inverse association with age throughout adulthood. Longitudinal TCD follow-up may help to further determine the role of intracranial flow parameters in the neurovascular risk assessment of adults with SCD.

No relevant conflicts of interest to declare.