Sickle Cell Disease (SCD)


Sickle cell disease (SCD) is an autosomal recessive disease caused by a single amino acid substitution (glutamic acid is replaced by valine) at the sixth position of the β-globin chain.1 The abnormal hemoglobin due to this substitution (HbS) causes erythrocyte deformation (sickling). SCD is characterized clinically by hemolytic anemia and cycles of microvascular vaso-occlusion, which result in end-organ ischemia-reperfusion damage and infarction.

The primary goal of treatment is to prevent short- and long-term complications of SCD. Disease-specific treatments include hydroxycarbamide (also known as hydroxyurea), transfusion therapy, and hematopoietic stem cell transplant (HSCT). Currently, HSCT is the only treatment for SCD that is potentially curative.

Clinical Practice Guidelines

To develop evidence-based guidelines that patients, clinicians, and other healthcare professionals can follow in their decision making, the American Society of Hematology (ASH) assembled 5 multidisciplinary panels that included specialists in adult and pediatric hematology, cardiology, pulmonology, nephrology, neurology, neuroradiology, pediatric psychology, psychiatry, emergency medicine, adult and pediatric pain medicine, and transfusion medicine. All specialists had clinical and research expertise on the particular guideline topics. Patient representatives were also included in the panels. With support from The Mayo Clinic Evidence-Based Practice Research Program, the ASH panels developed 5 sets of SCD clinical practice guidelines covering cardiopulmonary and kidney disease, cerebrovascular disease, transfusion, transplantation, and pain management.

Cardiopulmonary and Kidney Disease

The ASH 2019 guidelines for “sickle cell disease: cardiopulmonary and kidney disease” include a total of 13 recommendations for the screening, diagnosis, and management of cardiopulmonary and renal complications of SCD .2

  • The ASH guideline panel recommends a blood pressure goal of 130/80 mm Hg or lower over a goal of 140/90 mm Hg or lower for adults with SCD because of the negative effect of hypertension on patient outcomes, particularly among African American patients.2
  • The ASH guideline panel recommends that asymptomatic patients with SCD not undergo screening for pulmonary hypertension, abnormal lung function, or sleep disorders. However, patients with SCD should be carefully evaluated for signs and symptoms of cardiopulmonary disease suggesting the need for diagnostic testing.2
  • In adults with SCD and a first unprovoked or recurrent provoked venous thromboembolism (VTE), the ASH guideline panel suggests indefinite anticoagulation over shorter, defined periods of anticoagulation. The panel also suggests defined periods of anticoagulation (3-6 months) over indefinite anticoagulation in adults with SCD and a first surgically or nonsurgically provoked VTE.2

Cerebrovascular Disease

The ASH 2020 guideline panel for “sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults” agreed on 19 recommendations, with evidence-based strategies to prevent, diagnose, and treat central nervous system complications of SCD in low-, middle-, and high-income settings.3

  • The ASH guideline panel recommends screening via brain scans to assess the risk for a silent stroke, given the high prevalence of silent cerebral infarcts in children and adults with HbSS or HbSβ0 thalassemia. Depending on the screening findings, children can receive regular blood transfusions to reduce the risk for a new stroke, another silent stroke, or both. In addition, screening can identify children who have already had a silent stroke and are therefore eligible for school-based resources and other types of educational support.3
  • In a high-income setting (where regular blood transfusion therapy, typically every 3-4 weeks, is feasible), the ASH guideline panel recommends regular blood transfusions for at least a year (vs no transfusion) with the intent to keep maximum HbS levels below 30% and maintain hemoglobin levels above 9.0 g/dL to reduce the risk for stroke in children who have HbSS or HbSβ0 thalassemia (ages 2-16 years) and abnormal transcranial Doppler (TCD) velocities.3
  • In low- and middle-income settings (where regular blood transfusion therapy and chelation therapy may not be available or affordable), the ASH guideline panel suggests hydroxyurea therapy at a fixed dose of at least 20 mg/kg per day or the maximum tolerated dose for children (ages 2-16 years) with HbSS, HbSβ0 thalassemia, or compound heterozygous SCD who have abnormal findings on TCD screening.3
  • 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 a delay of longer than 2 hours after the acute onset of  neurological symptoms.3

Management of Acute and Chronic Pain

The ASH 2020 guideline panel for “sickle cell disease: management of acute and chronic pain” agreed on 18 evidence-based recommendations to facilitate the management of acute and chronic pain in individuals living with SCD.4

  • For adults and children who have SCD and present to an acute care setting with acute pain related to SCD, the ASH guideline panel recommends rapid (within 1 hour of emergency department arrival) assessment and the administration of analgesia, with frequent reassessments (every 30-60 minutes) to optimize pain control.4
  • Patients with chronic pain may benefit from a personalized treatment strategy while beginning or discontinuing chronic opioid medication. Opioid decisions should be based on the risks vs benefits of opioids; they should also take into account the individual’s function and goals, and potential to derive long-term benefit. Non-opioid pain medications may be explored as part of a comprehensive pain treatment strategy for people with chronic pain.4
  • In addition to pharmaceuticals, clinicians treating people with SCD and acute pain can use massage, yoga, virtual reality, and guided audiovisual relaxation.4
  • Clinicians treating people with SCD and chronic pain can use Cognitive Behavioral Therapy and other integrative methods (eg, acupuncture, massage therapy) along with pharmaceuticals as part of a comprehensive disease and pain management plan.4
  • The ASH guideline panel suggests that chronic monthly transfusion treatment not be used as a first-line method to prevent or reduce repeated episodes of acute pain in adults and children who have SCD and experience recurrent acute pain.4

Stem Cell Transplantation

The ASH 2021 guideline panel for “sickle cell disease: stem cell transplantation” agreed on a total of 8 recommendations to help patients and providers assess how individuals with SCD should consider the timing and type of HSCT.5

  • In individuals with SCD who have had a stroke or are at very high risk of having a stroke, HSCT should be considered over the standard of care (transfusion). Furthermore, transplant should be considered for all patients with a neurological injury who have a matched sibling donor.5
  • The ASH guidelines suggest transplant from a matched sibling donor over the standard of care for individuals with frequent pain and recurring episodes of acute chest syndrome.5
  • The ASH guideline panel suggests transplant from alternative donors only in the context of a clinical study of persons with an indication for HSCT who do not have a matched sibling donor.5
  • Because of the risk for irreversible SCD-related organ damage, which increases with age, the ASH guideline panel suggests that patients with an indication for transplant undergo the procedure with cells from a matched donor early in life.5

Transfusion Support

The ASH 2020 guideline panel for “sickle cell disease: transfusion support” developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and the management of alloimmunization, DHTRs, and iron overload.6

  • Patients who have SCD and require transfusions should receive red blood cells that have undergone profiling more comprehensive than that used in typical blood type testing procedures.6
  • Immunosuppressive therapies should be used in certain situations, such as  when the sudden and urgent need for a transfusion arises in a patient who is at high risk for an immunological reaction to the transfusion, which is a serious complication that can develop after a blood transfusion.6

References

  1. Ballas SK, Kesen MR, Goldberg MF, et al. Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management. Scientific World J. 2012;2012:949535. doi:10.1100/2012/949535
  2. Liem RI, Lanzkron S, D Coates T, et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease. Blood Adv. 2019;3(23):3867-3897. doi:10.1182/bloodadvances.2019000916
  3. 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. doi:10.1182/bloodadvances.2019001142
  4. Brandow AM, Carroll CP, Creary S, et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain. Blood Adv. 2020;4(12):2656-2701. doi:10.1182/bloodadvances.2020001851
  5. Kanter J, Liem RI, Bernaudin F, et al. American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation. Blood Adv. 2021;5(18):3668-3689. doi:10.1182/bloodadvances.2021004394C
  6. Chou ST, Alsawas M, Fasano RM, et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support. Blood Adv. 2020;4(2):327-355. doi:10.1182/bloodadvances.2019001143

Reviewed by Kyle Habet, MD, on 12/3/2021.