Clinical and haematological risk factors for cerebral macrovasculopathy in a sickle cell disease newborn cohort: a prospective study

Abstract

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.

Interleukin-10 haplotypes are not associated with acute cerebral ischemia or high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia

“…However, this finding differs from previous published studies, associating low IL-10 levels with vaso-occlusive crises, 16 osteomyelitis, 31 and acute chest syndrome 29 in patients with SCA. Furthermore, this contradicts a previous study showing that a lower serum IL-10 level is associated with ischemic stroke in the general population 32 …”

“…The overall frequency of IL10 haplotypes found in this study was similar to that reported in a recent study conducted in adult individuals with SCA from the northeastern region of Brazil 29 . The present study found slightly higher frequencies of haplotypes associated with high and intermediate IL10 expressions.…”

Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition

“…In a large cohort study, Belisario et al () reported that reticulocyte count was significantly associated with a high TCD velocity. Reticulocytes have been implicated in the aetiology of cerebral macrovasculopathy; they are markers of marrow activity and haemolysis, can cause endothelial activation and subsequent damage (Platt, ; Switzer et al , ; Kato et al , ; Sommet et al , ), and are thus likely contribute to abnormal cerebral rheology and vaso‐occlusion.…”

How I manage sickle cell patients with high transcranial doppler results

“…There has been great interest in looking at the clinical, laboratory and genetic factors that are associated with abnormal TCD. There is good evidence to support a higher risk of abnormal TCD for patients with low haemoglobin, high reticulocyte count, high systolic blood pressure, and upper and lower respiratory tract obstruction whilst presence of alpha thalassaemia and high fetal haemoglobin levels (Sommet et al , ) have a protective effect. Beyond these generally accepted markers, the evidence is largely conflicting and unclear.…”