Cerebrovascular events, including stroke, silent cerebral infarcts, and cognitive morbidity are among the most debilitating central nervous system (CNS) complications of sickle cell disease (SCD). Previous studies have shown that cognitive impairment induced by cerebrovascular events can significantly reduce quality of life for patients with SCD. As a result, updated clinical practice guidelines for the treatment of CNS complications in SCD are essential to ensure optimal clinical care.1

The American Society of Hematology (ASH) recently published new clinical guidelines on the prevention, diagnosis, and treatment of CNS complications for children and adults with SCD in Blood Advances. First author of the report and cochair of the guideline panel, Michael R. DeBaun, MD, MPH, of the department of pediatrics at the Vanderbilt-Meharry Center of Excellence in Sickle Cell Disease in Nashville, and his coauthors developed the evidence-based guidelines to inform clinicians who treat patients within the SCD community about common neurological complications associated with the inherited blood disorder.

“Approximately 95% of the children with SCD are born in low-middle income countries,” Dr DeBaun told Hematology Advisor. “Children and adults with SCD require life-long medical support to maximize their quality of life and to minimize the late health effects of [treatment].”

The panel established 19 recommendations addressing different aspects (Table) of cerebrovascular disease, 3 of which immediately affect clinical care, including:

  1. Use of hydroxyurea and transcranial Doppler (TCD) ultrasound screening for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sβ0 (HbSβ0) thalassemia living in low-middle–income settings
  2. Use of magnetic resonance imaging (MRI) of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSβ0 thalassemia
  3. Surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children

Table. Selected strong recommendations by the ASH Guideline Panel on cerebrovascular disease in children and adults with SCD1

For children with HbSS or HbSβ0 thalassemia, aged 2 to 16 years, the panel recommends annual TCD screening.
For Children with HbSS or HbSβ0 thalassemia, aged 2 to 16 years, who have abnormal TCD velocities and live in a high-income setting (where regular blood transfusion therapy, typically every 3-4 weeks, is feasible to maintain the maximum HbS level <30% and maintain the Hb level >9.0 g/dL), the panels recommends regular blood transfusion for at least a year (vs no transfusion) with the goal of keeping maximum HbS levels <30% and maintaining Hb levels >9.0 g/dL to reduce stroke risk.
For children or adults with SCD and acute neurological deficits, including TIA, the panel recommends prompt blood transfusion. The transfusion should be given immediately upon recognition of symptoms without delay beyond 2 hours of acute neurological symptom presentation. The type of transfusion (simple, modified exchange, or apheresis) is dependent on individual patient factors and local transfusion resources.
For children with HbSS or HbSβ0 thalassemia and a history of prior ischemic stroke, the panel recommends blood transfusion goals for secondary stroke prevention of increasing the hemoglobin >9 g/dL at all times and maintaining the HbS level at <30% of total hemoglobin until the time of the next transfusion.
Given the high prevalence of developmental delay and cognitive impairments in children with SCD, coupled with the guidelines set by the American Academy of Pediatrics, the panel recommends that clinicians supervising care of children with SCD conduct surveillance using simplified signaling questions for the following: Concerns about developmental delays in preschool-age children. Concerns about neurodevelopmental disorders in school-age children with SCD, such as academic or behavioral problems or symptoms of inattention, hyperactivity, or impulsivity.
For adults who have abnormal surveillance results suggesting cognitive impairment, the panel recommends formal referral to a psychologist or a primary care physician able to perform more in-depth cognitive evaluation.
For children with SCD and abnormal screening for developmental or cognitive status, the panel recommends the following: A developmental, cognitive, and medical evaluation to diagnose any related disorders and to identify modifiable risk factors for developmental delays or cognitive impairments. Following the cognitive domain-specific evidence-based guidelines for these conditions to provide appropriate interventions.
Given the high prevalence of silent cerebral infarcts in children with HbSS or HbSβ0 thalassemia (1 in 3), and their association with cognitive impairment, poor school performance, and future cerebral infarcts, the panel recommends at least a 1-time MRI screening, without sedation, to detect silent cerebral infarcts in early-school-age children, when MRI can commonly be performed without sedation.
Abbreviations: ASH = American Society of Hematology; Hb = hemoglobin; HbSβ0 = hemoglobin Sβ0; HbSS = hemoglobin SS; MRI = magnetic resonance imaging; SCD = sickle cell disease; TCD = transcranial Doppler; TIA = transient ischemic attack.

Several of the recommendations were conditional recommendations due to limited currently available evidence for some outcomes of interest. To read the detailed recommendations containing qualifying remarks, readers should refer to the full publication in Blood Advances.

While these guideines are pertinent to clinicians treating patients with SCD, the authors also emphasized the importance of educating patients and their family members about these recommendations to reduce the burden of cerebrovascular complications.

The panel acknowledged that some of these recommendations may not be applicable to low-middle-income settings given differences in clinical care settings.

Expert Perspectives: SCD Around the Globe

“I worked extensively with sickle cell patients in Africa for about a decade,” Dr DeBaun said. “The cost of curative therapies, particularly in West Africa, where the majority of children with SCD are born, coupled with the absence of expertise and supportive care  required, are [key] prohibitive barriers for [use of] these therapies in [this region].”

“Despite these challenges, many families of children with SCD seek curative therapies in high-income countries,” he explained. “Upon returning home, they cannot receive the same standard of care expected of all postcurative therapy patients.”

Related Articles

Elliott Vichinsky, MD, director of hematology/oncology at UCSF Benioff Children’s Hospital in Oakland, California, who is also a co-author on the guidelines, told Hematology Advisor, “in recent years, there has been a significant rise in patient mobility, leading to SCD cases throughout the world. Addressing key barriers, such as access to care, patient education, and high costs, will improve outcomes for patients with SCD around the globe.”

Reference

  1. DeBaun MR, Jordan LC, King AA, et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020;4(8):1554-1588.