Silent cerebral infarcts in sickle cell anemia: A risk factor analysis

Background. Silent infarcts have been reported in 17% of young patients with sickle cell disease and are associated with impaired performance on standardized psychometric tests. Risk factors for the development of these lesions have not been identified. Methods. Investigators in the Cooperative Study of Sickle Cell Disease performed a brain magnetic resonance imaging scan on sickle cell anemia patients age 5.9 years and older who had been followed according to the protocols of the Cooperative Study since birth. Individuals with a known history of cerebrovascular accident were excluded from this analysis. Patients with and without silent infarctions were compared with regard to clinical and laboratory parameters. Results. The study sample included 42 patients (18.3%) with silent infarcts. Patients who had silent infarcts were significantly more likely to have a clinical history of seizure and a lower painful event rate. Lower hemoglobin level, increased leukocyte count, elevated pocked red blood cell count, and SEN β(s) globin gene haplotype were associated also with the presence of silent infarcts. There was no relationship between silent infarcts and platelet count, fetal hemoglobin level, reticulocyte percentage, serum aspartate aminotransferase level, total bilirubin concentration, blood pressure, growth parameters, or presence of α-thalassemia. A multivariate model for silent infarction identified the following as risk factors: low pain event rate, history of seizure, leukocyte count ≥11.8 x 10⁹/L, and the SEN β(s) globin gene haplotype. Conclusions. Patients with risk factors for silent infarcts should be evaluated for cerebrovascular disease. If evidence of infarction is found, consideration must be given to therapeutic intervention. At present, the appropriate treatment has not been determined.