Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort.
Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Créteil newborn SCA cohort (n = 217 SS/Sβ(0)), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigen-genoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L × 10(9)/L increase, 95% CI 1.000-1.006; P = .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P = .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention.
Pediatrics, Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal of Créteil, 40 avenue de Verdun, Créteil, France. francoise.bernaudin@chicreteil.fr
Françoise
F
Bernaudin
Suzanne
S
Verlhac
Cécile
C
Arnaud
Annie
A
Kamdem
Sylvie
S
Chevret
Isabelle
I
Hau
Lena
L
Coïc
Emmanuella
E
Leveillé
Elisabeth
E
Lemarchand
Emmanuelle
E
Lesprit
Isabelle
I
Abadie
Nadia
N
Medejel
Fouad
F
Madhi
Sophie
S
Lemerle
Sandra
S
Biscardi
Josiane
J
Bardakdjian
Frédéric
F
Galactéros
Martine
M
Torres
Mathieu
M
Kuentz
Christelle
C
Ferry
Gérard
G
Socié
Philippe
P
Reinert
Christophe
C
Delacourt
D000755:Anemia, Sickle Cell / Q000000981:diagnostic imaging* / Q000628:therapy*; D002539:Cerebral Arterial Diseases / Q000151:congenital / Q000000981:diagnostic imaging* / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000000981:diagnostic imaging / Q000628:therapy; D018810:Magnetic Resonance Angiography / Q000009:adverse effects / Q000379:methods; D008297:Male; D015997:Neonatal Screening / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome; D017585:Ultrasonography, Doppler, Transcranial / Q000009:adverse effects / Q000379:methods* / Q000706:statistics & numerical data