A 5-Year-Old With a Headache, Limp, and Projectile Vomiting

Afif Harb, MD; Antoine Saliba, MD


June 10, 2020

The Stroke Prevention in Sickle Cell Anemia (STOP 1) trial was performed in 1998 with a goal of assessing the effect of transfusion therapy in preventing the first stroke episode in patients with sickle cell anemia.[7] In this study, 130 children with sickle cell anemia high risk for stroke (two measures on TCD ultrasonography), and comparable baseline characteristics were enrolled. Sixty-three children were randomly assigned to the intervention arm (receipt of transfusions), and 67 children were randomly assigned to the control arm (no receipt of transfusions).

The study was terminated early because it demonstrated such a large benefit of transfusion. A clinical alert was issued by the National Heart, Lung, and Blood Institute. The alert stated that screening and prophylactic transfusion must be performed in children with sickle cell anemia aged 2-16 years who are at high risk for stroke and have not yet had a stroke. The conclusions of the STOP 1 trial were clear: Long-term transfusions significantly reduce the risk for stroke in children with sickle cell anemia who have risk factors on TCD ultrasonography.

After the remarkable results of the STOP 1 trial, new questions were addressed, including when to start and stop blood transfusions in high-risk patients. The STOP 2 trial sought to determine the effect of discontinuing transfusions in patients with sickle cell anemia who were once at high risk for a stroke, had been receiving transfusions for more than 30 months, and currently had normal blood-flow velocities on TCD ultrasonography.[8] This study was stopped 2 years after initiation, when 79 children of a planned enrollment of 100 had undergone randomization.

Among the 41 children in whom transfusions were stopped, high-risk results on TCD ultrasonography developed in 14 and stroke developed in 2 others within an average of 4.5 months of the last transfusion. In contrast, no events of the composite endpoint occurred in the 38 children who continued to receive transfusions. The study team concluded that discontinuation of transfusion for the prevention of stroke in children with sickle cell anemia results in a high rate of reversion to abnormal blood-flow velocities on Doppler studies and stroke. Thus, stopping transfusions in patients who are at high risk of stroke is unsafe.

Moreover, an increase in serum ferritin was found, suggesting the development of iron overload in patients who are being treated with lifelong transfusions. Alloimmunization was seen, but no risk for infection was detected.

Owing to the conclusive results of the STOP 1 and STOP 2 trials, all patients with sickle cell anemia with abnormal blood-flow velocities on TCD ultrasonography were placed on lifelong transfusion therapy. Because the frequent transfusions cause iron to progressively accumulate in these patients, they began developing complications from iron overload.


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