Evaluation of Transcranial Doppler in 1135 Sickle Cell Disease Children From Brazil: What Is the Time Averaged Maximum Velocity for High Risk of Stroke Among HbSC Patients?

Sickle cell disease (SCD) is an autosomal recessive hereditary disorder, characterized by the presence of hemoglobin S (HbS), and a clinical multisystem involvement. Stroke is the most disabling complication of SCD and has an incidence around 11% and 2% in sickle cell anemia (HbSS) and SCD patients before the age of 20 respectively. The Transcranial Doppler (TCD) is a noninvasive and safe diagnostic technique to monitor the cerebral mean blood flow velocities of SCD identifying those at risk for developing stroke, enabling the prophylactic treatment with chronic transfusion regime. Despite the high incidence of stroke in HbSC patients when compared with the pediatric population without HbSC, few studies have evaluated flow velocities by TCD in this genotype. Values used for risk stratification of TCD were obtained from HbSS or HbS/βthalassemia patients; therefore, theoretically, these cannot be extrapolated to HbSC patients.

The aim of this study is to compare, by TDC, characteristics of cerebral blood flow among patients with HbSS, HbSC and HbS/βthalassemia.

A cross-sectional study was performed from May 2011 to April 2011 in 1135 SCD patients aged from 2 and 16 years, at seven Brazilian states. Patients were submitted to a TCD screening (using a single device Doppler, probe 2Mhz model Ezdop), being excluded those with a prior stroke event or under chronic transfusion regimen. Time averaged maximum velocity (Tamm) in the middle cerebral arteries and distal internal carotid was obtained according to STOP protocol. Patients were stratified by SCD genotype. The study was approved by the research board from the State Government and all parents or guardians provided written informed consent.

Females represented 46.3% (525) of the sample, and the mean age of 7.2±4.1 years. The Tamm at ACI/ACM was obtained at left and right respectively. In subjects with HbSS the velocity was of 131.7 cm/s and 130.7 cm/s; in patients with HbS/βthalassemia of 115.2 cm/s and 122.1 cm/s, and HbSC patients of 99.3 cm/s and 98.1 cm/s. Results of TDC were normal in 80.2% of SCD patients, conditional in 9.9%, 7.2% abnormal, 1.8% inconclusive, and 0.9% with low speed. The number of abnormal test, representing patients with a high risk for the occurrence of stroke among HbSS and β⁰thalassemia patients was 9.3%. This value was similar to the international literature that varies from 9.1% to 12.5%. One of the few studies that evaluated patients with HbSC through TCD was developed by Rees et al (2008) that analyzed 47 TCD from HbSC patients. The Tamm average found in the middle cerebral arteries was 94cm/s [12]. In this study, HbSC patients had an average Tamm of the middle cerebral arteries of 98.7 cm/s. Compared to patients with HbSS and Hb/βthalassemia, mean Tamm was significantly lower. Using rates of stroke risk in individuals with HbSS and HbS/βthalassemia, only 1.1% of HbSC patients would present high risk of stroke. However, differences in the mean Tamm in the middle cerebral arteries in HbSS patients (131.2 cm/s), HbS/βthalassemia (118.7 cm/s), and HbSC (98.7 cm/s), p<0.05, values suggest specific risk for HbSC patients was established. The average Tamm of middle cerebral artery/internal carotid distal in HbSC patients was 98.7 cm s with a standard deviation of 18.3 cm/s. Establishing standard deviations for HbSC patients, values above 135.3 cm/s could be considered high values for this population. In this case, considering as a cutoff point for HbSC patients speeds greater than 135.3 cm/s, 17 (6.2%) of individuals in our study would show high values. In the study of Rees, the Tamm who represented the 98th percentile was 128cm/s.

Approximately 9 to 10% of HbSS and HbS/βthalassemia individuals in our sample have a high risk for stroke occurrence. However, data from HbSC patients' needs to be studied prospectively in order to establish if there is different TCD velocities values for an increased risk for stroke, contributing to preventive measures implementation.

No relevant conflicts of interest to declare.