Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort

Pediatrics, Referral Center for Sickle Cell Disease, Centre Hospitalier Intercommunal of Créteil, 40 avenue de Verdun, Créteil, France.
Blood (Impact Factor: 10.45). 11/2010; 117(4):1130-40; quiz 1436. DOI: 10.1182/blood-2010-06-293514
Source: PubMed


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.

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Available from: Frederic Galacteros, Aug 24, 2015
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    • "G6PD deficiency (A‐genotype) in SCA is associated with lower Hb but not increased haemolysis (Nouraie et al, 2010). Reports of the effects of co‐inheritance of G6PD deficiency with CBFv, vasculopathy on magnetic resonance angiography and/or stroke risk are contradictory (Bernaudin et al, 2008, 2011; Rees et al, 2009; Miller et al, 2011; Thangarajh et al, 2012) and there are no data from patients resident in Africa. "
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    ABSTRACT: Transcranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co-inheritance in SCA of alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co-inheritance of these polymorphisms on CBFv in 601 stroke-free Tanzanian SCA patients aged <24 years. Homozygosity for alpha-thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild-type (β-coefficient -16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha-thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35-0·8] & RRR = 0·43 [95% CI:0·23-0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17-0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co-inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha-thalassaemia in reducing risk of abnormal CBFv.
    British Journal of Haematology 02/2014; 165(5). DOI:10.1111/bjh.12791 · 4.71 Impact Factor
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    • "Thrombospondin-1 and L-selectin are associated with silent cerebral infarct in children with sickle cell anaemia Silent cerebral infarction (SCI) is a prevalent problem in sickle cell anaemia (SCA, defined herein as HbSS or HbSB 0 thalassaemia); by age 6 years, 27% of children with SCA have had a SCI (Kwiatkowski et al, 2009) and by age 14 years, 37% (Bernaudin et al, 2011). Children with SCI are at greater risk for overt stroke, recurrent or progressive SCI, and impaired cognitive function than the general SCA population . "

    British Journal of Haematology 05/2013; 162(3). DOI:10.1111/bjh.12374 · 4.71 Impact Factor
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    • "The definition of SCI comprises both an abnormal MRI with absence of physical findings of overt stroke.2 Surprisingly SCD patients will have an incidence of SCI up to 27% by age 6 and 37% by age 14.16,17 Recent evidence suggests that adult SCD patients are prone to develop new and ongoing SCIs.2 The latter may on the one hand be the cause for poor intellectual performance in these patients and on the other hand either become progressive SCI or overt stroke disease. "
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    ABSTRACT: The aim of this paper is to correlate the extent of silent cerebral infarcts (SCIs) on magnetic resonance imaging (MRI) with the clinical severity of sickle cell disease (SCD) in adult patients. Twenty-four consecutive adult asymptomatic SCD patients (11 male and 13 female) with a mean age of 38.4 years (range 20-59) were submitted to brain MRI on a 1 Tesla Gyroscan Intera, Philips MR scanner with a dedicated head coil. The protocol consisted of TSE T2-weighted and FLAIR images on the axial and coronal planes. MRI readings were undertaken by two radiologists and consensus readings. Patients were compound heterozygotes (HbS/β-thal). The extent of SCIs was classified from 0-2 with 0 designating no lesions. Clinical severity was graded as 0-2 by the hematologist, according to the frequency and severity of vaso-occlusive crises. There was no statistically significant correlation between the severity of clinical disease and the extent of SCIs on MR imaging. The extent of SCI lesions did not differ statistically between younger and older patients. Patients receiving hydroxyurea had no statistically significant difference in the extent of SCI lesions. The extent of SCIs in heterozygous (HbS/β-thal) SCD patients is not age related and may be quite severe even in younger (<38.4 years) patients. However the extent of SCIs is not correlated with the severity of clinical disease.
    Hematology Reports 01/2013; 5(1):8-12. DOI:10.4081/hr.2013.e3
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