Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial Doppler ultrasonography. Intra-individual variation in blood flow velocities in cerebral arteries of children with sickle cell disease.
Blood transfusions prevent recurrent stroke in children with sickle cell anemia, but the value of transfusions in preventing a first stroke is unknown. We used transcranial Doppler ultrasonography to identify children with sickle cell anemia who were at high risk for stroke and then randomly assigned them to receive standard care or transfusions to prevent a first stroke.
                To enter the study, children with sickle cell anemia and no history of stroke had to have undergone two transcranial Doppler studies that showed that the time-averaged mean blood-flow velocity in the internal carotid or middle cerebral artery was 200 cm per second or higher. The patients were randomly assigned to receive standard care or transfusions to reduce the hemoglobin S concentration to less than 30 percent of the total hemoglobin concentration. The incidence of stroke (cerebral infarction or intracranial hemorrhage) was compared between the two groups.
                A total of 130 children (mean [+/-SD] age, 8.3+/-3.3 years) were enrolled; 63 were randomly assigned to receive transfusions and 67 to receive standard care. At base line, the transfusion group had a slightly lower mean hemoglobin concentration (7.2 vs. 7.6 g per deciliter, P=0.001) and hematocrit (20.4 vs. 21.7 percent, P=0.002). Ten patients dropped out of the transfusion group, and two patients crossed over from the standard-care group to the transfusion group. There were 10 cerebral infarctions and 1 intracerebral hematoma in the standard-care group, as compared with 1 infarction in the transfusion group -- a 92 percent difference in the risk of stroke (P<0.001). This result led to the early termination of the trial.
                Transfusion greatly reduces the risk of a first stroke in children with sickle cell anemia who have abnormal results on transcranial Doppler ultrasonography. Children with sickle cell disease (SCD) are at elevated risk of stroke. Risk increases with blood flow velocity in selected cerebral arteries, as measured by transcranial Doppler (TCD) ultrasound, and use of TCD to screen these patients is widely recommended. Interpretation of TCD results should be based on knowledge of intra-individual variation in blood flow velocity, information not currently available for sickle cell patients.
                Between 1995 and 2002, 4,141 subjects, 2-16 years old, with homozygous SCD or Sbeta0-thalasemmia and no history of stroke were screened with TCD, including 2,018 subjects screened in one clinical trial (STOP), 1,816 screened in another (STOP 2), and 307 screened in an interim ancillary prospective study. The 812 subjects with >or=2 examinations<6 months apart were selected for analysis, including 242 (29.8%) subjects with normal average velocities (i.e., <170 cm/sec), 350 (43.1%) subjects with conditional velocities (i.e., 170-199 cm/sec), and 220 (27.1%) subjects with abnormal velocities (i.e., >or=200 cm/sec). The intra-subject standard deviation of TCD velocity was estimated from the difference between velocities at the first two interpretable examinations on each subject.
                An intra-subject standard deviation of 14.9 cm/sec was obtained. Seven (0.9%) subjects had unusually large and unexplained differences between velocities at the two examinations (range of absolute differences: 69-112 cm/sec).
                While stroke risk is well demonstrated to increase with increasingly abnormal TCD velocity, given the relatively large intra-subject variability, one TCD examination is generally not sufficient to characterize stroke risk in this patient population.
                Copyright (c) 2007 Wiley-Liss, Inc.
These trials demonstrated a significantly reduced risk of stroke in participants receiving regular blood transfusions. Data from a follow-up trial indicate individuals may revert to former risk status if transfusion is discontinued. Degree of risk must be balanced against the burden of chronic transfusions. Further research is required examining the use of transfusion in preventing secondary stroke, and further defining risk factors for stroke, to avoid unnecessarily starting children on blood transfusions.