Sickle Cell Disease: Prevention, Diagnosis, and Treatment of Cerebrovascular Disease in Children and Adults

Publication Date: April 1, 2020
Last Updated: March 14, 2022

Recommendations

Primary stroke prevention for children with SCD living in low-middle– and high-income settings

For children with HbSS or HbSβ0 thalassemia (ages 2-16 years), the American Society of Hematology (ASH) guideline panel recommends annual TCD screening. ( Strong , Moderate )
607
For children who have compound heterozygous SCD other than HbSC and have evidence of hemolysis in the same range as those with HbSS, the ASH guideline panel suggests TCD screening. ( Conditional , Very Low )
607
For children with HbSS or HbSβ0 thalassemia (ages 2-16 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 hemoglobin level >9.0 g/dL), the ASH guideline panel recommends regular blood transfusion for at least a year (vs. no transfusion) with the goal of keeping maximum HbS levels below 30% and maintaining hemoglobin levels >9.0 g/dL to reduce the risk of stroke. ( Strong , Moderate )
607
For children who have compound heterozygous SCD other than HbSC, who have evidence of hemolysis in the same range as those with HbSS, an abnormal TCD velocity, and live in a high-income setting (where regular blood transfusion therapy is feasible), the ASH guideline panel suggests regular blood transfusion for at least a year (vs no transfusion) with the goal of keeping maximum HbS levels below 30% to reduce the risk of stroke. ( Conditional , Very Low )
607
For children with SCD (ages 2-16 years) and abnormal TCD results who have been receiving transfusion therapy for at least 1 year and are interested in stopping transfusion, according to the clinical trial risk stratification with an MRI and magnetic resonance angiography (MRA) of the brain, the ASH guideline panel suggests that hydroxyurea treatment at the maximum tolerated dose can be considered to substitute for regular blood transfusions. ( Conditional , Low )
607
For children (ages 2-16 years) with HbSS, HbSβ0 thalassemia, or compound heterozygous SCD who have abnormal TCD screening and live in low-middle-income settings (where regular blood transfusion therapy and chelation therapy are not available or affordable), the ASH guideline panel suggests hydroxyurea therapy with at least 20 mg/kg per day at a fixed dose or the maximum tolerated dose. ( Conditional , Low )
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Acute and timely treatment of suspected or confirmed ischemic stroke or TIA

For children or adults with SCD and acute neurological deficits, including transient ischemic attack (TIA), the ASH guideline 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. ( Strong , High )
607
For children or adults with SCD and acute neurological deficits including TIA, the ASH guideline panel suggests exchange transfusion vs simple transfusion. When exchange transfusion is not available within 2 hours of presentation for medical care and hemoglobin is ≤8.5 g/dL, simple transfusion can be performed to avoid delays in treatment while a manual exchange transfusion or an automated apheresis is planned. ( Conditional , Low )
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Secondary prevention of ischemic strokes in children and adults with HbSS or HbSβ0 thalassemia

For children with HbSS or HbSβ0 thalassemia and a history of prior ischemic stroke, the ASH guideline panel recommends blood transfusion goals for secondary stroke prevention of increasing the hemoglobin above 9 g/dL at all times and maintaining the HbS level at <30% of total hemoglobin until the time of the next transfusion. ( Strong , Low )
607
For adults and children with SCD, moyamoya syndrome, and a history of stroke or TIA, the ASH guideline panel suggests evaluation for revascularization surgery in addition to regular blood transfusion. ( Conditional , Moderate )
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Acute management of ischemic strokes and the use of tPA for adults with SCD presenting with stroke symptoms

For adults with SCD presenting with symptoms of acute ischemic stroke who are being evaluated for IV tissue plasminogen activator (tPA; age ≥18 years, no hemorrhage on computed tomography [CT] scan, within 4.5 hours of onset of symptoms/signs and without contraindications for thrombolysis), the ASH guideline panel suggests management using a shared decision-making approach that follows these principles:
  1. For all patients, the administration of tPA should not delay prompt simple or exchange blood transfusion therapy.
  2. Patients may be considered for IV tPA based on its established inclusion and exclusion criteria detailed in stroke management algorithms.
  3. The following factors suggest likely benefit from IV tPA: older age, atrial fibrillation, diabetes, hypertension, and hyperlipidemia. Management of younger patients without these risk factors should emphasize early transfusion.
  4. There are no validated risk stratification or reliable age cutoff criteria to guide the choice of initial therapy. IV tPA is not recommended for children with SCD (<18 years of age).
  5. IV tPA is not recommended for children with SCD (<18 years of age).
( Conditional , Very Low )
607

Screening for developmental delay or cognitive impairment in children and adults with SCD

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 ASH guideline panel recommends that clinicians supervising care of children with SCD conduct surveillance using simplified signaling questions for the following:
  1. Concerns about developmental delays in preschool-age children.
  2. Concerns about neurodevelopmental disorders in school-age children with SCD, such as academic or behavioral problems or symptoms of inattention, hyperactivity, or impulsivity.
( Strong , Low )
607
For children with SCD who have abnormal surveillance results suggesting increased risk for developmental delay or cognitive impairment, the ASH guideline panel recommends screening or referral for formal screening by a psychologist or a pediatrician able to perform screening with the available validated tools. ( Strong , Low )
607
Given the high prevalence of cognitive impairment in adults with SCD, coupled with the guidelines set by the American Academy of Neurology, the ASH guideline panel recommends that clinicians supervising care of adults with SCD conduct surveillance for cognitive impairment using simplified signaling questions. ( Strong , Low )
607
For adults who have abnormal surveillance results suggesting cognitive impairment, the ASH guideline panel recommends formal referral to a psychologist or a primary care physician able to perform more in-depth cognitive evaluation. ( Strong , Low )
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Cognitive rehabilitative strategy for children and adults with cognitive impairments

For children with SCD and abnormal screening for developmental or cognitive status, the ASH guideline panel recommends the following:
  1. A developmental, cognitive, and medical evaluation to diagnose any related disorders and to identify modifiable risk factors for developmental delays or cognitive impairments.
  2. Following the cognitive domain-specific evidence-based guidelines for these conditions to provide appropriate interventions.
( Strong , High )
607
For adults with SCD and abnormal screening for cognitive status, the ASH guideline panel recommends the following:
  1. Cognitive and medical evaluation to diagnose any related disorders and to identify modifiable risk factors for cognitive impairments.
  2. Following the cognitive domain-specific evidence-based guidelines for these conditions to provide appropriate interventions.
( Strong , High )
607

Screening for silent cerebral infarcts in children and adults with HbSS or HbSβ0 thalassemia

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 ASH guideline 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. ( Strong , Moderate )
607
Given the high prevalence of silent cerebral infarcts in adults with HbSS or HbSβ0 thalassemia (1 in 2) and their association with cognitive impairment, poor school performance, and future cerebral infarcts, the ASH guideline panel suggests at least a 1-time MRI screening without sedation to detect silent cerebral infarcts in adults with HbSS or HbSβ0 thalassemia. ( Conditional , Low )
607

Recommendation Grading

Disclaimer

Overview

Title

Sickle Cell Disease: Prevention, Diagnosis, and Treatment of Cerebrovascular Disease in Children and Adults

Authoring Organization

Publication Month/Year

April 1, 2020

Last Updated Month/Year

July 24, 2023

Document Type

Guideline

External Publication Status

Published

Country of Publication

US

Document Objectives

These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD.

 

Inclusion Criteria

Female, Male, Adolescent, Adult, Child, Older adult

Health Care Settings

Ambulatory, Hospital, Outpatient

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Diagnosis, Prevention, Management, Treatment

Diseases/Conditions (MeSH)

D000755 - Anemia, Sickle Cell, D002561 - Cerebrovascular Disorders

Keywords

sickle cell disease, cerebrovascular disease

Source Citation

DeBaun MR, Jordan LC, King AA, Schatz J, Vichinsky E, Fox CK, McKinstry RC, Telfer P, Kraut MA, Daraz L, Kirkham FJ, Murad MH. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults. Blood Adv. 2020 Apr 28;4(8):1554-1588. doi: 10.1182/bloodadvances.2019001142. PMID: 32298430; PMCID: PMC7189278.