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Extracranial arteriopathy develops progressively in children with sickle cell anemia (SCA) as early as 2 years of age and reaches a plateau around 10 years of age, according to the results of a systematic assessment of arteriopathy kinetics of the extracranial portion of the internal carotid artery (eICA) in a longitudinal cohort of children with sickle cell disease (SCD). Similar results were observed for intracranial arteriopathy. The findings were presented by Francoise Bernaudin, MD, of the Referral Center for Sickle Cell Disease, at CHIC Hospital, University Paris XII, in Créteil, France, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.
“Intracranial arteriopathy is detected by abnormal time-averaged mean of maximum velocities, confirmed by intracranial magnetic resonance angiography (MRA), while extracranial internal carotid arteriopathy is detected by abnormal high velocities [equal to and greater than] 160 cm/s, which are significantly associated with stenosis,” said Dr Bernaudin. “They are confirmed by cervical MRA, which can detect stenosis at the site of kinking, loop, or straight artery at the postbulbar location.”
In the study, Dr Bernaudin and colleagues aimed to evaluate and compare the cumulative incidence of intracranial and extracranial arteriopathy and associated risk factors in a longitudinal cohort of patients with SCD.
Children who were born between January 1988 and January 2018 were followed up at the Referral Center for Sickle Cell Disease until at least June 2012 and up to September 2019. The children included in the study were assessed annually using transcranial Doppler imaging and assessed at least once using cervical Doppler imaging.
In total, 493 children with SCD were included in the analysis (SCA, n=398; sickle cell/Sβ+ [SC/SB+], n=95). Median follow-up duration of the overall cohort was 10.6 years (range, 1.1-22.9). Six deaths occurred (5 patients with SCA at 2, 4, 7, 19, and 20 years, respectively, and 1 in a patient with SB+ at 13 years). Of the 385 patients with hemoglobin SS, 3 had ischemic stroke occurring at 1.5, 3, and 4.3 years of age, respectively.
The cumulative incidences of intracranial arteriopathy at 10 years of age (median follow-up) as indicated by time-averaged mean velocity (TAMV) of 200 cm/s or more were significantly different between children with SCA and those with SC/SB+ (27.6% vs 0.0%, respectively; P <.001), as were those for intracranial stenosis (11.1% vs 0.0%, respectively; P =.001). Cumulative incidence of intracranial stenosis according to intracranial TAMV history was 24.1% in those with a TAMV of 200 cm/s or more and 4.2% in those with a TAMV less than 200 (P <.001).
The cumulative incidences of extracranial arteriopathy at 10 years of age as indicated by TAMV of 160 cm/s or more at the eICA were significantly different between children with SCA and those with SC/SB+ (17.4% vs 1.1%, respectively; P <.001), as were those for eICA stenosis (12.3% vs 0.0%, respectively; P =.015). Cumulative incidence of extracranial stenosis according to eICA TAMV history was 47.8% in those with TAMV of 160 cm/s or more and 3.0% in those with TAMV less than 160 (P <.001). The cumulative incidence of eICA tortuosities was significantly different between children with SCA and those with SC/SB+ (30.3% vs 7.1%, respectively; P =.005).
Risk factors were analyzed in patients with isolated intracranial or extracranial arteriopathy. Anemia was a predictive risk factor for both intracranial and extracranial arteriopathy (per unit increase: hazard ratio [HR], 0.627; 95% CI, 0.493-0.797; P <.001 and HR, 0.84; 95% CI, 0.72-0.98; P =.031, respectively), and high white blood cell count (HR, 1.081; 95% CI, 1.031-1.133; P =.001) and reticulocytes (HR, 1.002; 95% CI, 1.000-1.005; P =.025) were risk factors for intracranial arteriopathy.
“Only children [with sickle cell anemia] are at risk for intra- and extracranial arteriopathy,” noted Dr Bernaudin. “Anemia is a predictive risk factor for intra- and extracranial arteriopathy, while white blood cells, reticulocyte counts, and [lactate dehydrogenase] are risk factors only for intracranial arteriopathy.”
“[A]ny treatment increasing hemoglobin level and decreasing hemolysis, such as hydroxyurea and voxelotor, should be efficient to decrease the risk of cerebral arteriopathy.”
Disclosure: Some authors have declared affiliations with or received funding from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
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Bernaudin F, Verlhac S, Arnaud C, et al. Cumulative incidences and risk factors for intra and extracranial cerebral arteriopathy in sickle cell disease children. Presented at: American Society of Hematology (ASH) 62nd Annual Meeting and Exposition; December 5-8, 2020. Abstract 503.