Abstract

Introduction

Stroke is a serious complication in Sickle Cell Disease (SCD) with an incidence of 11% by age 16 yrs and 24% by 45 yrs. In the Stroke Prevention Trial (STOP Trial) validity of the TransCranial Doppler (TCD) and threshold velocity ≥200 cm/sec were demonstrated to be useful in the prevention of stroke in pediatric patients with SCD. At present few data are available in adult patients. It is known that blood flow velocities detected with TransCranial Doppler (TCD) and TransCranial Color Doppler (TCCD) are comparable.

Aim

To compare transcranial blood flow velocities between SCD adult patients and healthy controls using TCCD with the insonation angle correction; to identify by TCCD the maximum mean Peak Systolic Velocity (PSV) in SCD adult patients as potential predictor of acute event or as an indicator of chronic progression of the disease; to evaluate Magnetic Resonance Imaging/Angiography (MRI/MRA) findings.

Patients and Methods

Fifty adult patients with SCD (aged >16 years) were enrolled, including14 Sickle Cell Anemia (SCA), 24 Sickle Cell Thalassemia (HbS-βThal) and 12 HbS/HbC. SCD adult patients and healthy subjects matched by gender, age and ethnicity (ratio of 2:1) were compared. SCD patients with epilepsy, pregnancy, HIV infection and bone marrow transplantation were excluded. The study was approved by Ethics Committee and all subjects gave written informed consent. Clinical evaluation, blood cell count, hemoglobin fractions by High Performance Liquid Chromatography (HPLC) and biochemical tests were evaluated. In both patients and controls Color and Duplex Doppler Sonography (CDDS) and TransCranial Color Doppler (TCCD) with angle correction were performed by the same physician to evaluate PSV, Pulsatility Index (PI) of the extracranial vessels (ICA and VA) and middle (MCA), anterior (ACA), posterior (PCA) cerebral arteries, carotid siphon (SIPH), vertebral (VA intracranial) and basilar (BAS) arteries following the STOP protocol. Furthermore, in all the patients 3.0T MRI/MRA was performed.

Results

Significant differences in Hb levels, Hct%, WBC, RBC, MCV, HbA2% and HbF% (p<0.001) were found comparing SCD group and controls, with a mean Hb values of 9.9±1.8 and 13.8±1.4 g/dl respectively. No neurological signs were reported, despite history of sickle crisis. PSVs in MCA, ACA, SIPH, PCA, intracranial VA, BAS were higher in SCD patients (p<0.001), in particular the mean PSV in MCA was 129.89±21.22 cm/sec in SCD patients and 110.71±14.96 cm/sec in controls. In SCD patients MCA velocities were correlated with Hb values, Ht%, RBC and HbS% (p<0.01), but independent from MCV, HbA2%, HbF%, reticulocytes, erythroblasts, WBC, iron status and hemolysis indices. In SCA patients higher velocities compared to HbS-βThal and HbS/HbC patients (140.55±12.90 cm/sec vs 128.48±22.37, p=0.013 and 119.394±22.51, p<0.011 respectively) were found. PI was normal in both SCD patients and controls, but statistically lower in SCD patients, (MCA, ACA, PCA, SIPH, VA intra- and extracranial, p<0.01). No differences in PI between the 3 SCD subgroups were found. PSVs percentile were calculated, considering pathological those above the 95°: MCA>164.18 cm/s; ACA>135.20 cm/s, SIPH>170.75 cm/s; PCA>99.67 cm/s; VA>101.50 cm/s; BAS>116.12 cm/s. Eight out of 50 SCD patients were found above the 95° percentile in any district, showing a more severe clinical phenotype. No stenosis were found in ICA by CDDS. SCD patients underwent to MRI/MRA to evaluate cerebral parenchymal lesions and vessel abnormalities respectively. In 11 patients (22%) vascular lesions, in 17 patients (34%) white aspecific lesions and in 9 patients (18%) cerebral atrophy were found. In 2 patients (4%) mild focal stenosis were detected.

Conclusions

TCCD velocities in adults SCD patients are lower than those provided by the STOP trial in children, confirming that the speeds disclose an age-related decline, however are higher than in healthy controls, in particular in SCA patients. According to our data, we could suggest as pathological cut off a MCA PSV value >160 cm/s. Moreover stenosis detected by MRA are not frequent as in young SCD patients. The peculiar alterations observed at MRI require further investigations.

Disclosures:

Cappellini:Novartis: Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity’s Board of Directors or advisory committees.

Author notes

*

Asterisk with author names denotes non-ASH members.

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