Lessons from the Stroke Prevention Trial in Sickle Cell Anemia (STOP) study

Area of Science:

• Pediatric Neurology
• Hematology
• Vascular Medicine

Background:

• Sickle cell disease (SCD) is a genetic blood disorder associated with a high incidence of ischemic stroke in children.
• Cerebral artery stenosis, particularly in the middle cerebral and intracranial internal carotid arteries, is a primary cause of stroke in pediatric SCD patients.
• Transcranial Doppler (TCD) ultrasonography enables noninvasive risk stratification for stroke in children with SCD.

Purpose of the Study:

• To evaluate the efficacy of chronic red blood cell transfusions in preventing a first-ever stroke in children with sickle cell disease.
• To compare the effectiveness of transfusion therapy against standard care for primary stroke prevention in this high-risk pediatric population.

Main Methods:

• A randomized clinical trial (Stroke Prevention in Sickle Cell Anemia - STOP study) involving 14 clinical centers.
• Screening of over 2000 children with SCD using TCD ultrasonography to identify those with elevated blood flow velocity indicating high stroke risk.
• Enrollment of 130 high-risk children into the trial, randomly assigned to receive either regular blood transfusions or standard care.
• Transfusion strategy aimed to reduce Hb S levels below 30%.

Main Results:

• Regular red cell transfusions led to a greater than 90% reduction in stroke incidence compared to the untreated risk of 10% per year.
• The study demonstrated a marked decrease in stroke events in the transfusion group, prompting early termination of the trial.
• Blinded adjudication of stroke events by remote neurologists ensured objective outcome assessment.

Conclusions:

• Chronic blood transfusion therapy is a highly effective strategy for primary stroke prevention in children with sickle cell disease and elevated stroke risk.
• The findings support widespread screening using TCD ultrasonography and prompt consideration of transfusion therapy for at-risk children aged 2-16.
• The National Heart, Lung, and Blood Institute issued a Clinical Alert based on these results, recommending screening and treatment protocols.