Investigators said disease-modifying therapies may change the treatment landscape of sickle cell disease (SCD).
Stroke is a common and potentially devastating complication of sickle cell disease (SCD), but it is possible to manage the risk with screening, monitoring, and carefully chosen interventions.
In a new review article, investigators from the University of North Carolina at Chapel Hill discussed the latest strategies and techniques for managing cerebrovascular complications of SCD. Their report was published in Journal of Blood Medicine.
Stroke and other cerebrovascular complications are common in people with SCD, noted the study authors. A study they highlighted found 11% of people with SCD experience a stroke by the age of 19 and 24% experience a stroke by age 45. They said stroke risk is highest among people with homozygous hemoglobin S (HbSS) disease and hemoglobin Sβ0 (HbSβ0) thalassemia.
Routine transcranial doppler screening (TCD) is the “cornerstone” of primary stroke prevention, the authors said.
“A landmark series of 283 TCDs in 190 patients with SCD found that stroke correlated with increasing blood flow velocity in the median cerebral arteries, a marker of vascular narrowing; strokes occurred in 7 of 23 participants with elevated velocity compared to none with normal velocity,” they noted.
Sometimes, it is not possible to obtain adequate TCDs due to issues such as interoperator variability or the inability to obtain accurate readings in the vertebrobasilar arteries, they said. In those cases, the authors use brain MRI and magnetic resonance angiography, although they cautioned that screening young children using these methods generally requires sedation.
When TCD velocities can be obtained, the investigators said readings above 200 cm/s suggest an increased risk of stroke. For those patients, early initiation of chronic red blood cell (RBC) transfusion is the standard stroke prevention tool. RBC transfusion is also key to managing acute stroke and secondary stroke prevention, they said.
However, RBC transfusion brings with it the risk of iron load and other complications.
“Close collaboration between the patient, the hematology team, and the transfusion medicine service is essential for prompt recognition and management of transfusion reactions, as well as prevention,” the authors noted.
For some patients, hydroxyurea can replace RBC transfusions, although the investigators said they only consider switching patients to hydroxyurea if their TCDs have normalized following chronic transfusion therapy. Hydroxyurea can also be an option for patients for whom transfusions are not feasible, they said.
The authors said silent cerebral infarction (SCI) is even more common than stroke. The complication can affect as many as 39% of children and half of adults, they said.
“Despite its name, SCI does manifest clinically as neurocognitive decline, difficulty with school and work performance, and other neuropsychological problems,” they said.
Chronic transfusion, and possibly hydroxyurea, can reduce the risk of stroke or SCI extension in children, although the authors said that option must be weighed against the burden of transfusions. Hydroxyurea may also help prevent SCI or its progression. The investigators said SCI management ultimately needs to be tailored to individual patients and based on careful neurocognitive evaluation.
Therapies that may have longer-term benefits were also outlined. The authors said hematopoietic stem cell transplantation (HSCT) decreases stroke risk in patients with SCD, but that the risks of HSCT should be carefully evaluated, particularly in an era where disease-modifying therapies are becoming available. Those disease-modifying drugs include voxelotor (Oxbryta) and crizanlizumab (Adakveo).
“The past several years have seen a sharp increase in new therapies for SCD, and ongoing clinical trials will evaluate the efficacy of medications like voxelotor and crizanlizumab for stroke prevention,” the authors wrote.
They said gene therapy might also be an option in the future, although the long-term benefits and risks of that approach have yet to be thoroughly explored.
“As we look toward the future of SCD management, we must not lose sight of the immense suffering caused by cerebrovascular disease for people with SCD and their families,” the authors concluded.
But they said clinicians also must remember the many barriers to equitable management of complications and the need for close collaboration between policymakers, providers, researchers, industry, and other stakeholders to overcome the “devastating burden” of SCD.
Light J, Boucher M, Baskin-Miller J, Winstead M. Managing the cerebrovascular complications of sickle cell disease: current perspectives. J Blood Med. 2023;14:279-293. doi:10.2147/JBM.S383472