The occurrence of strokes is on the rise among both adults and children with sickle cell disease (SCD), even though the Stroke Prevention Trial in Sickle Cell Anemia (STOP) has set care standards like blood transfusions and brain blood flow assessments for high-risk individuals. This information comes from a recent study published in Blood.
The occurrence of strokes is on the rise among both adults and children with sickle cell disease (SCD), even though the Stroke Prevention Trial in Sickle Cell Anemia (STOP) has set care standards like blood transfusions and brain blood flow assessments for high-risk individuals, according to a recent study published in Blood.
People with SCD, which is the most prevalent inherited blood disorder in the U.S., are more prone to cerebrovascular events (CVEs). This includes both ischemic and hemorrhagic strokes—cases where blood vessels to the brain become blocked or burst—as well as transient ischemic attacks (TIAs), which occur when a blood clot temporarily blocks a blood vessel without lasting damage.
The landmark STOP trial, conducted in 1998, showed that regular blood transfusions successfully lowered the number of cerebrovascular events like strokes in high-risk children with SCD, determined by abnormal blood flow detected through Transcranial Doppler (TCD) testing, which is a type of brain ultrasound.
In a broader, community-based analysis, Dr. Wun and his team discovered that the risk of stroke rises with age, doubling for every two decades.
“As hematologists, we are taught that young children face the highest stroke risk; however, this focus has diverted attention from adult patients,” stated Ted Wun, MD, associate dean for clinical and translational research at UC Davis School of Medicine and the lead author of the study. “There’s limited data on stroke occurrences in adults with SCD, leading us to apply findings from children to adults without knowing if that’s valid—whether the TCD thresholds for children are applicable to adults, and if TCD is effective for adult patients even though we rarely use it.”
The study utilized data from California’s Emergency Department Utilization (2005 — 2019) and Patient Discharge Data (1991 — 2019) to pinpoint 7,636 patients diagnosed with SCD. Among these, 733 patients (9.6%) had encountered at least one CVE, comprising 451 (5.9%) ischemic strokes, 227 (3%) hemorrhagic strokes, and 205 (2.7%) TIAs. Women and those hospitalized three or more times annually exhibited higher CVE rates.
The cumulative incidence of hemorrhagic strokes showed a remarkable 13-fold increase from age 20 to 60. Furthermore, despite a two-year period of reduced CVEs after the STOP trial’s publication, the highest rates of all CVEs were recorded among all age groups during the past decade, from 2010 to 2019.
“Even among children, who likely receive the best care for SCD in this country, these trends are contrary to what we would hope for,” remarked Dr. Wun. “These results suggest that the implementation of STOP guidelines has been ineffective.”
Dr. Wun and his team proposed that the rise in strokes since the STOP trial could be attributed to declining adherence to TCD screening guidelines, advancements in diagnosing ischemic strokes, low usage rates of blood transfusion therapies, or insufficient application of hydroxyurea, a medication often prescribed to help prevent blood cells from forming into sickle shapes. The researchers also explored modifiable risk factors for strokes and identified frequent hospital visits, hypertension, high cholesterol levels, and past TIAs as factors raising the risk of ischemic strokes. Additionally, patients with conditions such as acute chest syndrome, liver failure, and previous ischemic strokes were more likely to experience hemorrhagic strokes.
These updated findings on modifiable stroke risk factors “highlight the need for increased monitoring of high cholesterol, hypertension, and other risk factors in adults,” stated Olubusola Oluwole, MD, assistant professor at the University of Pittsburgh and the study’s primary author.
“Preventive measures known to reduce stroke risk in the general population are equally crucial for those with SCD,” Dr. Wun emphasized, particularly as individuals with SCD are living longer and facing heightened stroke risks.
The study acknowledges several limitations, including a lack of reliable data on tobacco use—which heightens stroke risk—and SCD genetic types. Moreover, the authors did not have access to imaging results to confirm stroke diagnoses. The rate of CVEs among patients in California may also be underestimated if strokes happened outside the state, deaths from strokes occurred prior to hospitalization, or if TIA symptoms were treated at home.
The researchers aim for this study to inspire more interventional and prospective research regarding stroke and SCD in adults.
