Sickle cell disease (SCD) is a group of inherited blood disorders affecting hemoglobin, the oxygen-carrying protein within red blood cells. Normally, red blood cells are round and flexible, moving easily through blood vessels. In SCD, a genetic mutation causes these cells to become rigid and crescent-shaped, resembling a sickle, under certain conditions. This abnormal shape and stiffness significantly increase the risk of stroke, which is one of the most serious complications of the disease.
How Sickle Cells Lead to Brain Blockage
The fundamental problem leading to stroke in SCD is the disruption of blood flow within the brain’s arteries, primarily resulting in an ischemic stroke. Sickled red blood cells are less flexible and prone to sticking to the inner lining of blood vessels, where they can clump together and form a “log jam” that blocks the flow of blood. This blockage prevents oxygen from reaching brain tissue, causing damage known as an ischemic stroke.
Sickled cells also cause chronic damage to the walls of large cerebral arteries, leading to a condition called vasculopathy. This damage triggers inflammation and cell proliferation within the vessel walls, causing them to narrow, a process known as stenosis. The combination of narrowed vessels and the presence of stiff, sticky red cells dramatically increases the likelihood of a complete occlusion and subsequent stroke.
While ischemic strokes are most common, a hemorrhagic stroke can also occur, though less frequently. This type of stroke involves bleeding into the brain tissue, often due to the rupture of blood vessels weakened by vasculopathy. Hemorrhagic strokes are more common in adults with SCD, while the ischemic pathway dominates in pediatric patients.
Identifying Vulnerable Patients and Early Screening
Stroke risk is not uniform across all patients with SCD, but is concentrated within specific age groups and genotypes. Children with the most severe form of the disease, sickle cell anemia (HbSS), or S-beta-zero thalassemia (Sβ0-thalassemia) face the highest risk. The peak window of vulnerability for a first overt stroke is typically between the ages of two and sixteen years old.
A specialized, non-invasive test called Transcranial Doppler (TCD) ultrasound is the standard tool used to screen for stroke risk in these children. TCD uses sound waves to measure the speed of blood flow through the major arteries at the base of the brain. This screening is recommended annually for children with sickle cell anemia between the ages of two and sixteen.
High blood flow velocity indicates that the arteries are narrowed (stenotic), forcing the blood to move faster to maintain adequate circulation. A time-averaged maximum mean velocity (TAMMV) of 200 cm/second or higher in the middle cerebral or internal carotid arteries identifies a child as high risk for stroke. Identifying this status through TCD allows for immediate preventative intervention.
Proactive Treatments to Reduce Stroke Risk
Once a patient is identified as high-risk by TCD screening, or after experiencing a stroke, proactive treatments are initiated to prevent future neurological events. The most effective and proven method for primary stroke prevention is chronic blood transfusion therapy. This treatment involves giving patients regular transfusions, typically every three to four weeks, of healthy donor blood.
The goal of chronic transfusion therapy is to dilute the concentration of sickled red blood cells in the patient’s bloodstream. Maintaining the proportion of sickle hemoglobin (HbS) below 30% effectively reduces the risk of a first stroke by over 90% in high-risk children. This therapy is a long-term commitment, however, and requires careful management of iron overload, which is a common side effect of frequent transfusions.
The medication Hydroxyurea is another preventative option, used for primary or secondary prevention. Hydroxyurea works by increasing the production of fetal hemoglobin (HbF), which prevents red blood cells from sickling. It can be an alternative for stroke prevention when chronic transfusion therapy is not feasible or desired.
Recognizing a Stroke and Emergency Response
Recognizing the signs of an acute stroke in a patient with SCD requires immediate attention, as time is a determining factor for effective intervention. The common acronym, FAST, is a helpful way to remember the most visible symptoms: Face drooping, Arm weakness, Speech difficulty, and Time to call emergency services. Other symptoms can include sudden confusion, severe headache, unsteadiness while walking, or unexplained numbness.
Any suspected stroke in a person with SCD is a medical emergency that requires immediate transport to a hospital that specializes in SCD care. Upon arrival, the initial management often includes an emergent exchange transfusion.
The exchange transfusion procedure quickly removes the patient’s sickled red blood cells and replaces them with healthy donor blood. This helps restore blood flow and oxygen delivery to the brain. Acute exchange transfusion, rather than clot-busting medications used for non-SCD stroke, is the treatment of choice for children with SCD experiencing a stroke.
Prompt action and specialized care are necessary to limit the extent of brain damage. Following the acute event, a long-term plan is established to prevent recurrence, which often involves chronic blood transfusion therapy.