Are patients with sickle cell disease at increased risk for cerebrovascular accidents (CVAs) or strokes?

From the Guidelines

Yes, patients with sickle cell disease are at significantly increased risk for cerebrovascular accidents (CVAs) or strokes, with approximately 11% experiencing a stroke by age 20, as supported by the most recent guideline from the American Heart Association/American Stroke Association 1. The underlying mechanism involves sickling of red blood cells, which causes them to become rigid and sticky, leading to vascular occlusion, endothelial damage, and hypercoagulability. These pathological changes can result in both ischemic strokes (from vessel occlusion) and hemorrhagic strokes (from weakened blood vessels). Prevention strategies include:

• Regular transcranial Doppler ultrasound screening in children to identify those at highest risk
• Chronic transfusion therapy to maintain hemoglobin S levels below 30% in high-risk patients, as recommended by the American Heart Association/American Stroke Association 1
• Hydroxyurea therapy may also reduce stroke risk by increasing fetal hemoglobin production and reducing sickling, as suggested by recent trials in Nigeria and Tanzania 1 For patients who have already experienced a stroke, indefinite transfusion therapy is typically recommended to prevent recurrence, with a Class of Recommendation (COR) of 1 and a Level of Evidence (LOE) of B-NR 1. Acute management of stroke in sickle cell patients includes prompt exchange transfusion to rapidly reduce the percentage of sickled cells while maintaining adequate hemoglobin levels. Key points to consider in the management and prevention of strokes in patients with sickle cell disease include:
• The importance of regular screening and monitoring for high-risk patients
• The role of chronic transfusion therapy and hydroxyurea in preventing strokes
• The need for prompt and effective acute management of stroke in sickle cell patients. It is essential to prioritize the most recent and highest quality studies, such as the 2024 guideline from the American Heart Association/American Stroke Association 1, when making recommendations for the management and prevention of strokes in patients with sickle cell disease.

From the Research

Sickle Cell Disease and Stroke Risk

• Patients with sickle cell disease (SCD) are at increased risk for cerebrovascular accidents (CVAs) or strokes, with 24% of SCD patients experiencing a stroke by the age of 45 years 2.
• The risk of stroke in SCD patients is associated with various factors, including prior transient ischemic attack, low steady-state hemoglobin values, and elevated systolic blood pressure 3.
• Transcranial Doppler ultrasonography screening can identify SCD patients at high risk of stroke, and chronic blood transfusion has been shown to reduce the risk of first stroke by 90% in these patients 4, 5.

Primary and Secondary Stroke Prevention

• Primary prevention of stroke in SCD patients can be achieved through transcranial Doppler ultrasonography screening and initiation of chronic transfusion therapy in high-risk patients 4, 5.
• Secondary stroke prevention in SCD patients is being studied, with hydroxyurea being tested as an alternative approach to chronic transfusion 6.
• Other potential strategies for stroke prevention in SCD patients include bone marrow transplantation, antiplatelet agents, and antithrombotic agents, although these have not been extensively tested 4, 3.

Pathophysiology and Management of Stroke in SCD

• The pathophysiology of stroke in SCD is complex and involves factors such as hemolytic anemia, nitric oxide metabolism, and genetic risk factors 6.
• Management of stroke in SCD patients requires a multidisciplinary approach, including neurology, hematology, and other specialties 3, 2.
• Recent advances in the understanding of the pathophysiology of stroke in SCD have led to improved management strategies, including the use of transcranial Doppler ultrasonography screening and hydroxyurea therapy 6, 2.