High reticulocyte count is an independent risk factor for cerebrovascular disease in children with sickle cell anemia

Transcranial Doppler ultrasonography (TCD) is an important way of detecting risk of ischemic stroke in children with sickle cell anemia.

A random sample of 262 FS-hemoglobin children from a newborn screening inception cohort in Brazil (1998-2005) was followed up to May 2009. Pulsed TCD followed STOP protocol. Children with mean blood flow velocity < 170 cm/sec in cerebral arteries were classified as low risk; between 170 and 184, low conditional risk; between 185 and 199, high conditional risk; and ≥ 200, high risk.

Median age, 6.2 years (2-11.2 years); 147 female; 13 children (5%) had ischemic stroke prior to TCD; 186/249 (74.7%) were classified as low risk; 19 (7.6%) as low conditional; 7 (2.8%) as high conditional; and 8 (3.2%) as high risk; inadequate tests, 11.6%. The probability of ischemic stroke at 10 years was 8.3% (SEM 2.3%); of stroke or high-risk TCD 15.6% (3.5%). Children with stroke or altered TCD (conditional and high risk) were compared to children with normal examinations. They were younger (P = 0.03), with lower hemoglobin (P = 0.003), higher leukocytosis (P = 0.015), and higher reticulocytosis (P < 0.001). Episodes per year of acute chest syndrome were also higher in that group, but not significantly (P = 0.09). Reticulocytosis remained the only significant variable upon multivariate analysis (P = 0.004). Basilar and middle cerebral artery velocities were significantly correlated (R = 0.55; P < 0.001).

Probability of stroke was similar to international reports; of belonging to high-risk group, lower. High-reticulocyte count was the most important factor associated with cerebrovascular disease. Basilar artery velocity > 130 cm/sec seems to be an indirect sign of an underlying cerebrovascular disease.