The incidence of stroke in adults and kids living with sickle cell disease continues to rise, regardless that the Stroke Prevention in Individuals with Sickle Cell Disease (STOP) study has established standards of care, reminiscent of blood transfusions and tests that measure cerebral blood flow in people deemed at high risk, in response to a study published today in Blood.

People living with SCD, essentially the most common inherited red blood cell disease in the USA, are particularly liable to cerebrovascular accidents (CVEs). These include ischemic or hemorrhagic strokes, when a blood vessel resulting in the brain is blocked by a blood clot or bursts, and transient ischemic attacks (TIAs), when a blood clot temporarily blocks a blood vessel resulting in the brain but doesn’t cause long-term damage.

STOP, a landmark clinical trial published in 1998, showed that chronic red blood cell transfusions effectively reduced the incidence of cerebrovascular events (CVEs) — reminiscent of strokes — in high-risk children with SCD, identified by abnormal blood flow measured by transcranial Doppler (TCD), a form of ultrasound scan of the brain.

In a real-world population study, Dr. Wun and his team found that the danger of stroke increases with age and doubles every 20 years.

As hematologists, our training emphasizes that the danger of stroke is highest in young children, but I feel in consequence, much less attention is paid to adult patients. There could be very little data on [stroke in adults living with SCD]So we just extrapolate what happens in children to adults, but we do not know whether that is appropriate or not – whether the TCD breakpoints in children might be applied to adults, whether TCD works in adult patients, and we just don’t try this.”

Ted Wun, MD, associate dean for clinical and translational research on the University of California, Davis School of Medicine and senior creator of the study

The researchers used data from California’s Emergency Department Utilization database (2005–2019) and Patient Discharge Data hospitalization (1991–2019) to discover 7,636 patients diagnosed with SCD. Of those patients, 733 (9.6%) experienced a minimum of one CVE, defined as ischemic stroke, hemorrhagic stroke, or TIA, with incidences of 451 (5.9%), 227 (3%), and 205 (2.7%), respectively. CVEs were more common in women and patients who were hospitalized three or more times per yr.

The cumulative incidence of hemorrhagic stroke increased 13-fold between ages 20 and 60. Moreover, despite a 2-year decline in CVEs following publication of the STOP study, the best rates of all CVEs occurred across all age groups up to now decade, 2010–2019.

“Even in children who probably receive one of the best SCD care on this country, these trends are the alternative of what we’d expect,” Dr. Wun said. “Based on these results, it seems that the STOP guidelines haven’t been implemented effectively.”

Dr. Wun and his team hypothesized that the rise in strokes after STOP could possibly be resulting from lower adherence to TCD screening guidelines, improved technology for diagnosing ischemic strokes, low rates of blood transfusion therapy, or low utilization of hydroxycarbamide, a drug commonly used to cut back the likelihood that blood cells will develop a sickle shape. The researchers also checked out modifiable risk aspects for stroke and located that aspects that increased the danger of ischemic stroke included frequent hospitalizations, hypertension, high cholesterol, and a previous TIA. Nonetheless, patients with risk aspects reminiscent of acute chest syndrome, liver failure, and a previous ischemic stroke were more prone to have a hemorrhagic stroke.

These updated data on modifiable risk aspects for stroke “underscore the necessity to concentrate on screening for prime cholesterol, hypertension and other risk aspects in adults,” said Dr. Olubusola Oluwole, an assistant professor on the University of Pittsburgh and the study’s lead creator.

“The preventive steps we all know help prevent stroke in the final population are only as vital for people living with SCD,” Dr. Wun added, especially as individuals with SCD live longer and their risk of stroke increases.

The study had several limitations, including the shortage of reliable data on tobacco use, which increases stroke risk, and SCD genotype. As well as, the authors didn’t have access to imaging reports and couldn’t radiographically confirm the stroke diagnosis. As well as, the CVE rate in patients in California could also be underestimated if patients had a stroke out of state, died of stroke before hospitalization, or if TIA symptoms were treated at home.

The researchers hope this study will encourage more interventional and prospective studies of stroke and SCD in adults.