G6PD deficiency and absence of α‐thalassemia increase the risk for cerebral vasculopathy in children with sickle cell anemia

Abstract

The aim of this study was to test the association between hematological/genetic factors and cerebral vasculopathy in children with sickle cell anemia (SCA). A group with cerebral vasculopathy (VASC) was composed of children who had stroke (n = 6), silent infarct (n = 11), or an abnormal transcranial Doppler (n = 5). Eighty-four patients had neither positive history of stroke or silent infarct, nor abnormal transcranial Doppler (NORM group). An intermediate group (COND; n = 15) was composed of SCA children with a conditional transcranial Doppler. Biological analyses were performed on samples obtained at steady state and before the beginning of any chronic treatment. The comparisons of the three groups demonstrated a protective effect of α-thalassemia against cerebral vasculopathy through its effects on hemoglobin and reticulocyte levels. Moreover, we observed higher frequency of G6PD deficiency in the VASC group compared with the other groups. Our study confirms the key role of α-thalassemia and G6PD status in the pathophysiology of cerebral vasculopathy in SCA children.

Associations of α-thalassemia and BCL11A with stroke in Nigerian, United States, and United Kingdom sickle cell anemia cohorts

“…4,12 Furthermore, the effects of α-thalassemia on cerebral vasculopathy and stroke risk in SCA have been mixed with some studies showing a protective benefit 13–18 while others have not. 10,19–21 In the University of Ibadan cohort of SCA patients, α-thalassemia was commonly observed but was not associated with a statistically significant reduction in the frequency of SCA-related complications.…”

Minireview: Clinical severity in sickle cell disease: the challenges of definition and prognostication

“…Some studies indicate no association between G6PD deficiency and stroke or cerebral vasculopathy, 17,23,24 while others do show an increased frequency of magnetic resonance index (MRI)- or transcranial Doppler (TCD)-defined cerebral vasculopathy. 18,25,26 These conflicting data limit the prognostic utility of G6PD deficiency.…”

Alpha‐thalassaemia promotes frequent vaso‐occlusive crises in children with sickle cell anaemia through haemorheological changes

“…8 The number of functional alpha-globin genes and the S -haplotypes are the two main genetic factors that are commonly determined in SCA. Alpha-thalassaemia has been shown to partly protect patients with SCA from developing glomerulopathy, [9][10][11] cerebral vasculopathy, 12,13 leg ulcers 14 and priapism. 5 The S -haplotypes have been described to modulate the levels of foetal haemoglobin (HbF), and thus the severity of the disease.…”