Silent cerebral infarction risk factors identified in sickle cell anemia
MedWire News: Low hemoglobin concentration and high systolic blood pressure (SBP) are risk factors for silent cerebral infarction (SCI) in children with sickle cell anemia (SCA), researchers report.
"SCI is the most common form of neurological injury among children with SCA, occurring in at least 27% prior to six years of life and 37% by 14 years of life," explain Michel DeBaun (Vanderbilt University, Nashville, Tennessee, USA) and colleagues.
SCIs in children with SCA are associated with an increased risk for future overt strokes and new or progressive SCI, but few studies have investigated clinical and laboratory factors associated with such infarcts.
To address this, DeBaun and team evaluated the clinical history and baseline laboratory variables in 814 children (aged 5-15 years) with SCA (HbSS or HbSβ° thalassemia) and no history of overt stroke or seizures. The children were all participants of the Silent Cerebral Infarct Multi-Center Clinical Trial, which was designed to determine the efficacy of blood transfusion therapy for prevention of recurrent SCI in children with SCA.
Magnetic resonance imaging (MRI) of the brain revealed that 251 (30.8%) children had SCI, defined as a MRI signal abnormality visible on two views on T2-weighted images (axial and coronal) and at least 3 mm in one dimension.
Compared with individuals without SCI, those with SCI were significantly more likely to be male (47.4 vs 58.2%), had significantly lower baseline hemoglobin concentration (8.25 vs 7.95 g/dL), and had significantly higher baseline systolic blood pressure (SBP 107.31 vs 109.41 mmHg).
Multivariable regression analysis confirmed that these three variables were significantly associated with risk for SCI.
Specifically, boys were 1.42 times more likely than girls to have SCI, individuals with baseline hemoglobin levels below 7.6 g/dL (lowest tertile) were 2.12 times more likely to have SCI than those with levels at or above 8.6 g/dL (highest tertile), and participants with a baseline SBP at or above 113 mmHg (highest tertile) were 1.73 time more likely to have SCI than those with a SBP below 104 mmHg.
Of note, incidence of pain or acute chest syndrome, baseline white blood cell count, percent hemoglobin F, and oxygen saturation levels were not associated with risk for SCI.
DeBaun and team say that low hemoglobin concentrations have also been associated with SCI in patients receiving dialysis and those with β-thalassemia intermedia.
"Although, the etiology of SCI is unknown, the consistent finding that anemia is a risk factor strongly implicates cerebral hemodynamic insufficiency as a central component," they write in the journal Blood.
They add that the biologic basis for the association between relatively high SBP measurements and SCI is also unknown, but may be due to a compromise in the compensatory autoregulation of vasodilation.
The researchers say that, based on their results, they cannot make definitive recommendations for preventing SCI.
"However, these findings provide the basis for further research focused on increasing the baseline hemoglobin concentration or attenuating factors that lead to relative high SBP measurements, as these are potentially modifiable risk factors for SCI," they conclude.
By Laura Dean