Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study
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Summary: Children with sickle cell disease ( SCD ) have a significant vascular morbidity, especially cerebral macrovasculopathy ( CV ), detectable by transcranial Doppler. This study aimed to identify risk factors for CV using longitudinal biological and clinical data in a SCD newborn cohort followed at the Robert Debre Reference centre ( n = 375 SS /Sβ 0 ). Median follow‐up was 6·8 years (2677 patient‐years). Among the 59 children presenting with CV , seven had a stroke. Overall, the incidence of CV was 2·20/100 patient‐years [95% confidence interval ( 95% CI ): 1·64–2·76] and the incidence of stroke was 0·26/100 patient‐years ( 95% CI : 0·07–0·46). The cumulative risk of CV by age 14 years was 26·0% ( 95% CI : 20·0‐33·3%). Risk factors for CV were assessed by a Cox model encompassing linear multivariate modelling of longitudinal quantitative variables. Years per upper‐airway obstruction [Hazard ratio ( HR ) = 1·47; 95% CI : 1·05–2·06] or bronchial obstruction ( HR = 1·76; 95% CI : 1·49–2·08) and reticulocyte count ( HR = 1·82 per 50 × 10 9 /l increase; 95% CI : 1·10–3·01) were independent risk factors whereas fetal haemoglobin level ( HR = 0·68 per 5% increase; 95% CI : 0·48–0·96) was protective. Alpha‐thalassaemia was not protective in multivariate analysis (ancillary analysis n = 209). Specific treatment for upper or lower‐airway obstruction and indirect targeting of fetal haemoglobin and reticulocyte count by hydroxycarbamide could potentially reduce the risk of CV .
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Of 375 children with sickle cell anemia or HbS-β0 thalassemia followed in a longitudinal prospective study, 59 had cerebrovascular disease or a stroke at a mean age of 4.4 years, and HbF was protective (HR: 0.68; 95% CI: 0.48-0.96).
“Of 375 children with sickle cell anemia or Figure 1.HbF distribution in sickle erythrocytes from 3 patients with 20% HbF.An example of 3 possible distributions of HbF/F-cell in 1000 cells from 3 individuals with mean HbF levels of 20%.The y axis represents numbers of cells, and the x axis represents HbF concentration in 5-pg increments.In red are cells likely to be least protected from HbS polymer”
From Fetal hemoglobin in sickle cell anemia (2020) · cites this paper as [69]
The cohort table lists 375 children, and the Cerebral vasculopathy and stroke section reports 59 with cerebral vasculopathy, including seven who had a stroke. The paper gives 4.4 years as the median age at cerebral vasculopathy diagnosis, not the mean. Its risk-factor table reports HbF as protective against cerebral vasculopathy (HR 0.68, 95% CI 0.48–0.96, per 5% increase). (LLM, conf=0.90)
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- Authors
- Sommet, J., Alberti, C., Couque, N., Verlhac, S., Haouari, Z., Mohamed, D., François, M., Missud, F., Holvoet, L., Elmaleh, M., Ithier, G., Denjean, A., Elion, J., Baruchel, A., & Benkerrou, M.
- Affiliations
- Inserm (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Hôpital Robert-Debré (FR)
- Hôpital Robert‐Debré Service d'Hématologie AP‐HP Paris France
- Hôpital Robert‐Debré Service d'ORL AP‐HP Paris France
- Sorbonne Paris Cité (FR)
- Hôpital Robert‐Debré UF de Génétique Moléculaire AP‐HP Paris France
- Corresponding author
- Sommet, Julie
- ORCID
- Venue
- British Journal of Haematology
- Publisher
- Wiley
- Published
- 2016-01-05
- Volume
- 172
- Issue
- 6
- Pages
- 966-977
- ISSN
- 0007-1048 (ISSN-L)
- 1365-2141
- OpenAlex
- W2222089707
- Cited by
- 38
- References
- 70
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 6 · 2016: 3
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Haematology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal Health and Biochemistry
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Keywords
- sickle cell disease, stroke, risk factors, reticulocyte count, fetal hemoglobin, upper airway obstruction, bronchial obstruction, alpha-thalassemia, hydroxyurea, transcranial Doppler, hematological parameters
- MeSH terms
- Anemia, Sickle Cell, Cerebral Arterial Diseases, Female, Fetal Hemoglobin, Follow-Up Studies, Humans, Infant, Newborn, Lung Diseases, Obstructive, Male, Prospective Studies, Risk Factors, alpha-Thalassemia, Ultrasonography, Doppler, Transcranial, Erythrocyte Transfusion, Stroke
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