Prophylactic Transfusions Prevent Strokes in Vulnerable Sickle Cell Disease
abstract & commentary
Source: Adams RJ, et al. Prevention of a first stroke by transfusions in children with sickle cell anemia and abnormal results on transcranial doppler ultrasonography. N Engl J Med 1998;339:5-11.
Stroke is an infrequent but devastating complication of sickle cell anemia. In a previous study of 315 sickle cell patients (N Engl J Med 1992;326:605-610), Adams showed that transcranial Doppler blood flow velocities exceeding 200 cm/sec in the ICA or MCA predicted an increased risk for stroke. The multicenter study, Stroke Prevention Trial in Sickle Cell Anemia (STOP), was undertaken using transcranial Doppler to test whether periodic transfusion would lower stroke risk.
During two years of screening, 3929 transcranial Doppler studies were performed on 1934 children ages 2-16 with sickle cell anemia or sickle thalassemia. To be considered abnormal, mean blood-flow velocity had to be at least 200 cm/sec in either the ICA or MCA. Two hundred six children had two or more abnormal studies and were, therefore, considered eligible for the study. Because of either ineligibility or drop out, only 130 children (60 boys, 70 girls) were enrolled. Sixty-three were randomized to receive transfusions and 67 to standard care. The transfusion goal was a target hemoglobin S concentration of less than 30% total hemoglobin. Once established, children received maintenance transfusions every 3-4 weeks for a median follow-up period of 22.2 months compared to 18.3 months for the standard care group. The end point was cerebral infarction as determined by blinded evaluators based upon MRI and clinical criteria. Eleven children in the standard care group and one child in the treatment group had strokes.
The risk of stroke was 92% lower in the transfusion group (P < 0.001). The rate of stroke in the standard care group was 10% per year. In 10 of 11 children, the strokes were large vessel (carotid territory) infarctions. Two patients were left with major disability, five had mild-moderate impairments, and three were discharged without disability. Because of the high rate of stroke in the standard care group, the study was stopped 16 months earlier than planned so that transfusions could be offered to the standard care group.
Commentary
This study of SCA patients found both a high rate of stroke in children with abnormal results on TCD (the higher the blood flow velocities, the higher the risk of stroke) and a beneficial effect of transfusion to reduce Hemoglobin S concentration. Transfusions have been proven effective in preventing recurrent strokes in SCA patients.2 The present treatment trial has established a role for prophylactic transfusions in children with TCD evidence of intracranial arterial stenosis. The study does not, however, establish how long transfusions must be continued to prevent strokes. In the current trial, the risk of stroke was high, about 10% per annum, without treatment. Whether stroke risk remains at this level indefinitely is unknown. Therefore, if long-term prophylactic transfusion therapy is necessary in all such SCA patients, the benefits of treatment may be limited by the cost and complications of treatment. Nevertheless, Adams et al have made a noteworthy advance in the non-invasive diagnosis and treatment of stroke-prone SCA patients. Further studies, no doubt, will answer the questions this study has raised.
References
1. Ohene-Frempong K, et al. Cerebrovascular accidents in sickle cell disease: Rates and risk factors. Blood 1998;91:288-294.
2. Pegelow CH, et al. Risk of recurrent stroke in patients with sickle cell disease treated with erythrocyte transfusions. J Pediatr 1995;126:896-899.
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